{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T09:46:39Z","timestamp":1794217599256,"version":"4.8.0"},"reference-count":230,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T00:00:00Z","timestamp":1686873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology & Therapeutics"],"published-print":{"date-parts":[[2023,9]]},"DOI":"10.1016\/j.pharmthera.2023.108480","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T21:18:19Z","timestamp":1686950299000},"page":"108480","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":151,"special_numbering":"C","title":["Targeting PCSK9 to tackle cardiovascular disease"],"prefix":"10.1016","volume":"249","author":[{"given":"Sandra","family":"Hummelgaard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim Pold","family":"Vilstrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Gustafsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Glerup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Weyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.pharmthera.2023.108480_bb0005","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.atherosclerosis.2012.04.006","article-title":"Identification and characterization of new gain-of-function mutations in the PCSK9 gene responsible for autosomal dominant hypercholesterolemia","volume":"223","author":"Abifadel","year":"2012","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0010","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/ng1161","article-title":"Mutations in PCSK9 cause autosomal dominant hypercholesterolemia","volume":"34","author":"Abifadel","year":"2003","journal-title":"Nature Genetics"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0015","doi-asserted-by":"crossref","DOI":"10.1126\/science.aaf7000","article-title":"Genetic identification of familial hypercholesterolemia within a single U.S. health care system","volume":"354","author":"Abul-Husn","year":"2016","journal-title":"Science"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0020","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/s41569-018-0098-5","article-title":"Safety and efficacy of statin therapy","volume":"15","author":"Adhyaru","year":"2018","journal-title":"Nature Reviews. Cardiology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0025","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/j.drudis.2022.01.014","article-title":"Development of small-molecule PCSK9 inhibitors for the treatment of hypercholesterolemia","volume":"27","author":"Ahamad","year":"2022","journal-title":"Drug Discovery Today"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0030","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.cca.2013.03.017","article-title":"The genetic spectrum of familial hypercholesterolemia in Pakistan","volume":"421","author":"Ahmed","year":"2013","journal-title":"Clinica Chimica Acta"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0035","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1172\/JCI61919","article-title":"Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice","volume":"122","author":"Ai","year":"2012","journal-title":"The Journal of Clinical Investigation"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0040","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/humu.9383","article-title":"Novel mutations of the PCSK9 gene cause variable phenotype of autosomal dominant hypercholesterolemia","volume":"26","author":"Allard","year":"2005","journal-title":"Human Mutation"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0045","doi-asserted-by":"crossref","first-page":"13796","DOI":"10.1021\/acs.jmedchem.0c01084","article-title":"Series of novel and highly potent cyclic peptide PCSK9 inhibitors derived from an mRNA display screen and optimized via structure-based design","volume":"63","author":"Alleyne","year":"2020","journal-title":"Journal of Medicinal Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0050","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1016\/j.jacc.2015.08.871","article-title":"Characterization of the first PCSK9 gain of function homozygote","volume":"66","author":"Alves","year":"2015","journal-title":"Journal of the American College of Cardiology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0055","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1083\/jcb.93.3.523","article-title":"Surface distribution and recycling of the low density lipoprotein receptor as visualized with antireceptor antibodies","volume":"93","author":"Anderson","year":"1982","journal-title":"The Journal of Cell Biology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0060","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0092-8674(77)90022-8","article-title":"Role of the coated endocytic vesicle in the uptake of receptor-bound low density lipoprotein in human fibroblasts","volume":"10","author":"Anderson","year":"1977","journal-title":"Cell"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0065","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.118.010838","article-title":"Pretreatment with PCSK9 inhibitor protects the brain against cardiac ischemia\/reperfusion injury through a reduction of neuronal inflammation and amyloid beta aggregation","volume":"8","author":"Apaijai","year":"2019","journal-title":"Journal of the American Heart Association"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0075","series-title":"PCSK9 expression summary","author":"Atlas","year":"2023"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0080","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1097\/CCM.0000000000004487","article-title":"Proprotein convertase Subtilisin\/Kexin type 9 loss-of-function is detrimental to the juvenile host with septic shock","volume":"48","author":"Atreya","year":"2020","journal-title":"Critical Care Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0085","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1093\/cvr\/cvaa254","article-title":"PCSK9 and LRP5 in macrophage lipid internalization and inflammation","volume":"117","author":"Badimon","year":"2021","journal-title":"Cardiovascular Research"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0090","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.chembiol.2022.12.003","article-title":"Clearance of plasma PCSK9 via the asialoglycoprotein receptor mediated by heterobifunctional ligands","volume":"30","author":"Bagdanoff","year":"2023","journal-title":"Cell Chemical Biology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0095","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1016\/S0140-6736(10)61350-5","article-title":"Efficacy and safety of more intensive lowering of LDL cholesterol: A meta-analysis of data from 170,000 participants in 26 randomised trials","volume":"376","author":"Baigent","year":"2010","journal-title":"Lancet"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0100","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.numecd.2019.09.012","article-title":"Platelet function and activation markers in primary hypercholesterolemia treated with anti-PCSK9 monoclonal antibody: A 12-month follow-up","volume":"30","author":"Barale","year":"2020","journal-title":"Nutrition, Metabolism, and Cardiovascular Diseases"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0105","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1161\/ATVBAHA.119.313247","article-title":"Ser-phosphorylation of PCSK9 (Proprotein convertase Subtilisin-Kexin 9) by Fam20C (family with sequence similarity 20, member C) kinase enhances its ability to degrade the LDLR (low-density lipoprotein receptor)","volume":"39","author":"Ben Djoudi Ouadda","year":"2019","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0110","doi-asserted-by":"crossref","first-page":"48865","DOI":"10.1074\/jbc.M409699200","article-title":"NARC-1\/PCSK9 and its natural mutants: Zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol","volume":"279","author":"Benjannet","year":"2004","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0115","doi-asserted-by":"crossref","first-page":"30561","DOI":"10.1074\/jbc.M606495200","article-title":"The proprotein convertase (PC) PCSK9 is inactivated by furin and\/or PC5\/6A: Functional consequences of natural mutations and post-translational modifications","volume":"281","author":"Benjannet","year":"2006","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0120","doi-asserted-by":"crossref","first-page":"40965","DOI":"10.1074\/jbc.M110.154815","article-title":"Effects of the prosegment and pH on the activity of PCSK9: Evidence for additional processing events","volume":"285","author":"Benjannet","year":"2010","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0125","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1161\/01.ATV.0000204337.81286.1c","article-title":"Missense mutations in the PCSK9 gene are associated with hypocholesterolemia and possibly increased response to statin therapy","volume":"26","author":"Berge","year":"2006","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0130","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1074\/jbc.M808363200","article-title":"Structural and biochemical characterization of the wild type PCSK9-EGF(AB) complex and natural familial hypercholesterolemia mutants","volume":"284","author":"Bottomley","year":"2009","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0135","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.atherosclerosis.2007.07.019","article-title":"Familial hypercholesterolaemia in Portugal","volume":"196","author":"Bourbon","year":"2008","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0140","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1159\/000442976","article-title":"Increased plasma PCSK9 levels are associated with reduced endotoxin clearance and the development of acute organ failures during sepsis","volume":"8","author":"Boyd","year":"2016","journal-title":"Journal of Innate Immunity"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0145","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.chembiol.2021.08.012","article-title":"Identification of a PCSK9-LDLR disruptor peptide with in vivo function","volume":"29","author":"Brousseau","year":"2022","journal-title":"Cell Chemical Biology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0150","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/0092-8674(83)90052-1","article-title":"Recycling receptors: The round-trip itinerary of migrant membrane proteins","volume":"32","author":"Brown","year":"1983","journal-title":"Cell"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0155","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1126\/science.3513311","article-title":"A receptor-mediated pathway for cholesterol homeostasis","volume":"232","author":"Brown","year":"1986","journal-title":"Science"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0160","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1084\/jem.20112322","article-title":"Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo","volume":"209","author":"von Br\u00fchl","year":"2012","journal-title":"The Journal of Experimental Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0165","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1021\/acschembio.9b00899","article-title":"Design of organo-peptides as bipartite PCSK9 antagonists","volume":"15","author":"Burdick","year":"2020","journal-title":"ACS Chemical Biology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0170","doi-asserted-by":"crossref","first-page":"18609","DOI":"10.1074\/jbc.M115.647180","article-title":"Amyloid precursor-like protein 2 and sortilin do not regulate the PCSK9 convertase-mediated low density lipoprotein receptor degradation but interact with each other","volume":"290","author":"Butkinaree","year":"2015","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0175","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/j.jacc.2017.11.069","article-title":"PCSK9 as a positive modulator of platelet activation","volume":"71","author":"Camera","year":"2018","journal-title":"Journal of the American College of Cardiology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0180","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.atherosclerosis.2008.10.007","article-title":"Mutation S462P in the PCSK9 gene reduces secretion of mutant PCSK9 without affecting the autocatalytic cleavage","volume":"203","author":"Cameron","year":"2009","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0185","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1093\/hmg\/ddl077","article-title":"Effect of mutations in the PCSK9 gene on the cell surface LDL receptors","volume":"15","author":"Cameron","year":"2006","journal-title":"Human Molecular Genetics"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0190","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1111\/j.1365-2796.2007.01915.x","article-title":"Characterization of novel mutations in the catalytic domain of the PCSK9 gene","volume":"263","author":"Cameron","year":"2008","journal-title":"Journal of Internal Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0195","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1161\/ATVBAHA.109.194191","article-title":"PCSK9 dominant negative mutant results in increased LDL catabolic rate and familial hypobetalipoproteinemia","volume":"29","author":"Cariou","year":"2009","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0200","doi-asserted-by":"crossref","first-page":"9820","DOI":"10.1073\/pnas.0903849106","article-title":"A proprotein convertase subtilisin\/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates","volume":"106","author":"Chan","year":"2009","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0205","doi-asserted-by":"crossref","first-page":"2961","DOI":"10.1016\/j.jacc.2019.03.513","article-title":"Efficacy and safety of evolocumab in chronic kidney disease in the FOURIER trial","volume":"73","author":"Charytan","year":"2019","journal-title":"Journal of the American College of Cardiology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0210","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/j.jacc.2005.01.051","article-title":"A common PCSK9 haplotype, encompassing the E670G coding single nucleotide polymorphism, is a novel genetic marker for plasma low-density lipoprotein cholesterol levels and severity of coronary atherosclerosis","volume":"45","author":"Chen","year":"2005","journal-title":"Journal of the American College of Cardiology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0215","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.00444","article-title":"SEC24A deficiency lowers plasma cholesterol through reduced PCSK9 secretion","volume":"2","author":"Chen","year":"2013","journal-title":"Elife"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0220","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s11745-014-3895-6","article-title":"PCSK9 is present in human cerebrospinal fluid and is maintained at remarkably constant concentrations throughout the course of the day","volume":"49","author":"Chen","year":"2014","journal-title":"Lipids"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0225","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/ng1509","article-title":"Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9","volume":"37","author":"Cohen","year":"2005","journal-title":"Nature Genetics"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0230","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1056\/NEJMoa054013","article-title":"Sequence variations in PCSK9, low LDL, and protection against coronary heart disease","volume":"354","author":"Cohen","year":"2006","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0235","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1126\/science.1239101","article-title":"Genetics. Simple genetics for a complex disease","volume":"340","author":"Cohen","year":"2013","journal-title":"Science"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0240","doi-asserted-by":"crossref","first-page":"6211","DOI":"10.1074\/jbc.M508582200","article-title":"Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory element-binding protein 1c","volume":"281","author":"Costet","year":"2006","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0245","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.3233\/JAD-170993","article-title":"PCSK9 concentrations in cerebrospinal fluid are not specifically increased in Alzheimer\u2019s disease","volume":"62","author":"Courtemanche","year":"2018","journal-title":"Journal of Alzheimer\u2019s Disease"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0255","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/nsmb1235","article-title":"Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia","volume":"14","author":"Cunningham","year":"2007","journal-title":"Nature Structural & Molecular Biology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0260","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1161\/ATVBAHA.115.306032","article-title":"PCSK9 induces CD36 degradation and affects long-chain fatty acid uptake and triglyceride metabolism in adipocytes and in mouse liver","volume":"35","author":"Demers","year":"2015","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0265","doi-asserted-by":"crossref","first-page":"10805","DOI":"10.1074\/jbc.M113.453373","article-title":"Characterization of proprotein convertase subtilisin\/kexin type 9 (PCSK9) trafficking reveals a novel lysosomal targeting mechanism via amyloid precursor-like protein 2 (APLP2)","volume":"288","author":"DeVay","year":"2013","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0270","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/j.jacl.2017.06.005","article-title":"A case of hypocholesterolemia and steatosis in a carrier of a PCSK9 loss-of-function mutation and polymorphisms predisposing to nonalcoholic fatty liver disease","volume":"11","author":"Di Filippo","year":"2017","journal-title":"Journal of Clinical Lipidology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0275","doi-asserted-by":"crossref","first-page":"15282","DOI":"10.1038\/s41598-017-15543-x","article-title":"Identification and in vitro characterization of two new PCSK9 gain of function variants found in patients with familial hypercholesterolemia","volume":"7","author":"Di Taranto","year":"2017","journal-title":"Scientific Reports"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0280","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1093\/cvr\/cvy079","article-title":"PCSK9 regulates expression of scavenger receptors and ox-LDL uptake in macrophages","volume":"114","author":"Ding","year":"2018","journal-title":"Cardiovascular Research"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0285","doi-asserted-by":"crossref","first-page":"7100","DOI":"10.7150\/thno.45939","article-title":"NLRP3 inflammasome via IL-1\u03b2 regulates PCSK9 secretion","volume":"10","author":"Ding","year":"2020","journal-title":"Theranostics"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0290","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1194\/jlr.M003566","article-title":"Strong induction of PCSK9 gene expression through HNF1alpha and SREBP2: Mechanism for the resistance to LDL-cholesterol lowering effect of statins in dyslipidemic hamsters","volume":"51","author":"Dong","year":"2010","journal-title":"Journal of Lipid Research"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0295","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1161\/01.ATV.0000134621.14315.43","article-title":"Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia","volume":"24","author":"Dubuc","year":"2004","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0300","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1194\/jlr.M900273-JLR200","article-title":"A new method for measurement of total plasma PCSK9: Clinical applications","volume":"51","author":"Dubuc","year":"2010","journal-title":"Journal of Lipid Research"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0305","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1097\/SHK.0000000000000682","article-title":"Differential expression of PCSK9 modulates infection, inflammation, and coagulation in a murine model of sepsis","volume":"46","author":"Dwivedi","year":"2016","journal-title":"Shock"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0310","doi-asserted-by":"crossref","first-page":"4257","DOI":"10.1074\/jbc.M110.192104","article-title":"In vivo evidence that furin from hepatocytes inactivates PCSK9","volume":"286","author":"Essalmani","year":"2011","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0315","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1161\/01.ATV.0000255311.26383.2f","article-title":"A novel loss of function mutation of PCSK9 gene in white subjects with low-plasma low-density lipoprotein cholesterol","volume":"27","author":"Fasano","year":"2007","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0320","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2019.11130","article-title":"A genetic approach to the association between PCSK9 and sepsis","volume":"2","author":"Feng","year":"2019","journal-title":"JAMA Network Open"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0325","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1093\/eurheartj\/ehx144","article-title":"Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European atherosclerosis society consensus panel","volume":"38","author":"Ference","year":"2017","journal-title":"European Heart Journal"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0330","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1056\/NEJMoa1604304","article-title":"Variation in PCSK9 and HMGCR and risk of cardiovascular disease and diabetes","volume":"375","author":"Ference","year":"2016","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0335","doi-asserted-by":"crossref","first-page":"20502","DOI":"10.1074\/jbc.M701634200","article-title":"Effects of pH and low density lipoprotein (LDL) on PCSK9-dependent LDL receptor regulation","volume":"282","author":"Fisher","year":"2007","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0340","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.bbalip.2017.05.002","article-title":"APP, APLP2 and LRP1 interact with PCSK9 but are not required for PCSK9-mediated degradation of the LDLR in vivo","volume":"1862","author":"Fu","year":"2017","journal-title":"Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0345","doi-asserted-by":"crossref","first-page":"15880","DOI":"10.1073\/pnas.1005743107","article-title":"Extracellular DNA traps promote thrombosis","volume":"107","author":"Fuchs","year":"2010","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0350","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/S0969-2126(01)00225-8","article-title":"The prosegment-subtilisin BPN\u2019 complex: Crystal structure of a specific \u2019foldase","volume":"3","author":"Gallagher","year":"1995","journal-title":"Structure"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0355","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1194\/jlr.M087189","article-title":"Cell-associated heparin-like molecules modulate the ability of LDL to regulate PCSK9 uptake","volume":"60","author":"Galvan","year":"2019","journal-title":"Journal of Lipid Research"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0360","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1016\/S0140-6736(20)32332-1","article-title":"Efficacy and safety of lowering LDL cholesterol in older patients: A systematic review and meta-analysis of randomised controlled trials","volume":"396","author":"Gencer","year":"2020","journal-title":"Lancet"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0365","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.ebiom.2018.11.032","article-title":"Impact of PCSK9 loss-of-function genotype on 1-year mortality and recurrent infection in sepsis survivors","volume":"38","author":"Genga","year":"2018","journal-title":"EBioMedicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0370","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1093\/protein\/gzv008","article-title":"Characterisation of de novo mutations in the C-terminal domain of proprotein convertase subtilisin\/kexin type 9","volume":"28","author":"Geschwindner","year":"2015","journal-title":"Protein Engineering, Design & Selection"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0375","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1016\/S0140-6736(17)32290-0","article-title":"Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: A prespecified secondary analysis of the FOURIER trial","volume":"390","author":"Giugliano","year":"2017","journal-title":"Lancet"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0380","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/path.4630","article-title":"Local effects of human PCSK9 on the atherosclerotic lesion","volume":"238","author":"Giunzioni","year":"2016","journal-title":"The Journal of Pathology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0385","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.cmet.2013.12.006","article-title":"The hypercholesterolemia-risk gene SORT1 facilitates PCSK9 secretion","volume":"19","author":"Gustafsen","year":"2014","journal-title":"Cell Metabolism"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0390","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/s41467-017-00568-7","article-title":"Heparan sulfate proteoglycans present PCSK9 to the LDL receptor","volume":"8","author":"Gustafsen","year":"2017","journal-title":"Nature Communications"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0395","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S1665-2681(19)31564-9","article-title":"Familial hypobetalipoproteinemia in a hospital survey: Genetics, metabolism and non-alcoholic fatty liver disease","volume":"10","author":"Guti\u00e9rrez-Cirlos","year":"2011","journal-title":"Annals of Hepatology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0400","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1161\/CIRCULATIONAHA.115.020912","article-title":"The role of Proprotein convertase Subtilisin\/Kexin type 9 in nephrotic syndrome-associated hypercholesterolemia","volume":"134","author":"Haas","year":"2016","journal-title":"Circulation"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0405","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.amjcard.2007.02.057","article-title":"Relation of PCSK9 mutations to serum low-density lipoprotein cholesterol in childhood and adulthood (from the Bogalusa heart study)","volume":"100","author":"Hallman","year":"2007","journal-title":"The American Journal of Cardiology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0410","doi-asserted-by":"crossref","first-page":"14604","DOI":"10.1073\/pnas.0703402104","article-title":"The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain","volume":"104","author":"Hampton","year":"2007","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0415","article-title":"Genetic testing of Korean familial hypercholesterolemia using whole-exome sequencing","volume":"10","author":"Han","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0420","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1038\/s41431-022-01107-9","article-title":"Genetic analysis of the PCSK9 locus in psychological, psychiatric, metabolic and cardiovascular traits in UK Biobank","volume":"30","author":"Hay","year":"2022","journal-title":"European Journal of Human Genetics"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0425","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.bbrc.2011.02.023","article-title":"Removal of acidic residues of the prodomain of PCSK9 increases its activity towards the LDL receptor","volume":"406","author":"Holla \u00d8","year":"2011","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0430","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.atherosclerosis.2007.07.022","article-title":"Identification and characterization of two non-secreted PCSK9 mutants associated with familial hypercholesterolemia in cohorts from New Zealand and South Africa","volume":"196","author":"Homer","year":"2008","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0435","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1517\/14712598.2012.748743","article-title":"Anti-PCSK9 therapies for the treatment of hypercholesterolemia","volume":"13","author":"Hooper","year":"2013","journal-title":"Expert Opinion on Biological Therapy"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0440","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.atherosclerosis.2006.08.039","article-title":"The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population","volume":"193","author":"Hooper","year":"2007","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0445","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1161\/CIRCGENETICS.115.001129","article-title":"Characterization of autosomal dominant hypercholesterolemia caused by PCSK9 gain of function mutations and its specific treatment with alirocumab, a PCSK9 monoclonal antibody","volume":"8","author":"Hopkins","year":"2015","journal-title":"Circulation. Cardiovascular Genetics"},{"issue":"Suppl","key":"10.1016\/j.pharmthera.2023.108480_bb0450","doi-asserted-by":"crossref","first-page":"S172","DOI":"10.1194\/jlr.R800091-JLR200","article-title":"PCSK9: A convertase that coordinates LDL catabolism","volume":"50","author":"Horton","year":"2009","journal-title":"Journal of Lipid Research"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0455","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1172\/JCI0215593","article-title":"SREBPs: Activators of the complete program of cholesterol and fatty acid synthesis in the liver","volume":"109","author":"Horton","year":"2002","journal-title":"The Journal of Clinical Investigation"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0460","doi-asserted-by":"crossref","first-page":"12027","DOI":"10.1073\/pnas.1534923100","article-title":"Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes","volume":"100","author":"Horton","year":"2003","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0465","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s11010-014-2259-0","article-title":"Lipopolysaccharide augments the uptake of oxidized LDL by up-regulating lectin-like oxidized LDL receptor-1 in macrophages","volume":"400","author":"Hossain","year":"2015","journal-title":"Molecular and Cellular Biochemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0470","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ijcard.2016.11.064","article-title":"Increased sortilin and its independent effect on circulating proprotein convertase subtilisin\/kexin type 9 (PCSK9) in statin-naive patients with coronary artery disease","volume":"227","author":"Hu","year":"2017","journal-title":"International Journal of Cardiology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0475","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1002\/humu.21660","article-title":"Genetic variation in APOB, PCSK9, and ANGPTL3 in carriers of pathogenic autosomal dominant hypercholesterolemic mutations with unexpected low LDL-Cl Levels","volume":"33","author":"Huijgen","year":"2012","journal-title":"Human Mutation"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0480","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1161\/01.ATV.20.4.1089","article-title":"Genetic localization to chromosome 1p32 of the third locus for familial hypercholesterolemia in a Utah kindred","volume":"20","author":"Hunt","year":"2000","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0485","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1126\/science.1059344","article-title":"Structural mechanism for statin inhibition of HMG-CoA reductase","volume":"292","author":"Istvan","year":"2001","journal-title":"Science"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0490","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1194\/jlr.M700443-JLR200","article-title":"Sterol-dependent regulation of proprotein convertase subtilisin\/kexin type 9 expression by sterol-regulatory element binding protein-2","volume":"49","author":"Jeong","year":"2008","journal-title":"Journal of Lipid Research"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0495","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.953845","article-title":"Sex difference in circulating PCSK9 and its clinical implications","volume":"13","author":"Jia","year":"2022","journal-title":"Frontiers in Pharmacology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0500","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1053\/j.ajkd.2013.10.042","article-title":"Plasma PCSK9 in nephrotic syndrome and in peritoneal dialysis: A cross-sectional study","volume":"63","author":"Jin","year":"2014","journal-title":"American Journal of Kidney Diseases"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0505","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCULATIONAHA.122.063372","article-title":"Orally bioavailable macrocyclic peptide that inhibits binding of PCSK9 to the low density lipoprotein receptor","author":"Johns","year":"2023","journal-title":"Circulation."},{"key":"10.1016\/j.pharmthera.2023.108480_bb0510","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1093\/eurheartj\/ehv707","article-title":"Safety and efficacy of LY3015014, a monoclonal antibody to proprotein convertase subtilisin\/kexin type 9 (PCSK9): A randomized, placebo-controlled phase 2 study","volume":"37","author":"Kastelein","year":"2016","journal-title":"European Heart Journal"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0515","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1016\/j.jacc.2016.03.520","article-title":"Diagnostic yield and clinical utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia","volume":"67","author":"Khera","year":"2016","journal-title":"Journal of the American College of Cardiology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0520","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1056\/NEJMp1614154","article-title":"Oligonucleotide therapeutics - A new class of cholesterol-lowering drugs","volume":"376","author":"Khvorova","year":"2017","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0525","doi-asserted-by":"crossref","first-page":"8279","DOI":"10.1074\/jbc.M112.421370","article-title":"Low density lipoprotein binds to proprotein convertase subtilisin\/kexin type-9 (PCSK9) in human plasma and inhibits PCSK9-mediated low density lipoprotein receptor degradation","volume":"288","author":"Kosenko","year":"2013","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0530","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1086\/500615","article-title":"A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol","volume":"78","author":"Kotowski","year":"2006","journal-title":"American Journal of Human Genetics"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0535","doi-asserted-by":"crossref","first-page":"473","DOI":"10.3945\/jn.116.235069","article-title":"Nutritional and lipid modulation of PCSK9: Effects on cardiometabolic risk factors","volume":"147","author":"Krysa","year":"2017","journal-title":"The Journal of Nutrition"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0540","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1194\/jlr.M051326","article-title":"Alirocumab inhibits atherosclerosis, improves the plaque morphology, and enhances the effects of a statin","volume":"55","author":"K\u00fchnast","year":"2014","journal-title":"Journal of Lipid Research"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0545","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.atherosclerosis.2012.11.009","article-title":"Proprotein convertase subtilisin-kexin type 9 is elevated in proteinuric subjects: Relationship with lipoprotein response to antiproteinuric treatment","volume":"226","author":"Kwakernaak","year":"2013","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0550","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1073\/pnas.0712064105","article-title":"Molecular basis for LDL receptor recognition by PCSK9","volume":"105","author":"Kwon","year":"2008","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0555","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1172\/JCI29383","article-title":"Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice","volume":"116","author":"Lagace","year":"2006","journal-title":"The Journal of Clinical Investigation"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0560","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1210\/jc.2009-0141","article-title":"Genetic and metabolic determinants of plasma PCSK9 levels","volume":"94","author":"Lakoski","year":"2009","journal-title":"The Journal of Clinical Endocrinology and Metabolism"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0565","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1093\/eurheartj\/ehx260","article-title":"The AT04A vaccine against proprotein convertase subtilisin\/kexin type 9 reduces total cholesterol, vascular inflammation, and atherosclerosis in APOE*3Leiden.CETP mice","volume":"38","author":"Landlinger","year":"2017","journal-title":"European Heart Journal"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0570","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.ajhg.2014.01.010","article-title":"Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol","volume":"94","author":"Lange","year":"2014","journal-title":"American Journal of Human Genetics"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0575","doi-asserted-by":"crossref","first-page":"3281","DOI":"10.1210\/jc.2016-1206","article-title":"PCSK9 R46L loss-of-function mutation reduces lipoprotein(a), LDL cholesterol, and risk of aortic valve stenosis","volume":"101","author":"Langsted","year":"2016","journal-title":"The Journal of Clinical Endocrinology and Metabolism"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0580","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1161\/CIRCULATIONAHA.115.018531","article-title":"Circulating Proprotein convertase Subtilisin\/Kexin type 9 (PCSK9) predicts future risk of cardiovascular events independently of established risk factors","volume":"133","author":"Leander","year":"2016","journal-title":"Circulation"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0585","article-title":"Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels","volume":"12","author":"Lee","year":"2017","journal-title":"PLoS One"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0590","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1111\/j.0009-9163.2004.0238.x","article-title":"Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia","volume":"65","author":"Leren","year":"2004","journal-title":"Clinical Genetics"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0595","doi-asserted-by":"crossref","first-page":"10588","DOI":"10.1038\/s41598-019-46745-0","article-title":"Reduced Proprotein convertase subtilisin\/kexin 9 (PCSK9) function increases lipoteichoic acid clearance and improves outcomes in gram positive septic shock patients","volume":"9","author":"Leung","year":"2019","journal-title":"Scientific Reports"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0600","doi-asserted-by":"crossref","first-page":"28885","DOI":"10.1074\/jbc.M109.052407","article-title":"Hepatocyte nuclear factor 1alpha plays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine","volume":"284","author":"Li","year":"2009","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0605","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1042\/BJ20070664","article-title":"Secreted PCSK9 promotes LDL receptor degradation independently of proteolytic activity","volume":"406","author":"Li","year":"2007","journal-title":"The Biochemical Journal"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0610","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1161\/ATVBAHA.116.308456","article-title":"Familial hypercholesterolemia phenotype in Chinese patients undergoing coronary angiography","volume":"37","author":"Li","year":"2017","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0615","first-page":"1133","article-title":"A novel mutation in proprotein convertase subtilisin\/kexin type 9 gene leads to familial hypercholesterolemia in a Chinese family","volume":"123","author":"Lin","year":"2010","journal-title":"Chinese Medical Journal"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0620","doi-asserted-by":"crossref","first-page":"43482","DOI":"10.1074\/jbc.M112.380618","article-title":"Furin-cleaved proprotein convertase subtilisin\/kexin type 9 (PCSK9) is active and modulates low density lipoprotein receptor and serum cholesterol levels","volume":"287","author":"Lipari","year":"2012","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0625","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s41586-020-2911-7","article-title":"Inhibition of PCSK9 potentiates immune checkpoint therapy for cancer","volume":"588","author":"Liu","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0630","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1038\/embor.2011.205","article-title":"Mechanistic implications for LDL receptor degradation from the PCSK9\/LDLR structure at neutral pH","volume":"12","author":"Lo Surdo","year":"2011","journal-title":"EMBO Reports"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0635","doi-asserted-by":"crossref","DOI":"10.3389\/fcvm.2021.639727","article-title":"PCSK9 functions in atherosclerosis are not limited to plasmatic LDL-cholesterol regulation","volume":"8","author":"Luquero","year":"2021","journal-title":"Frontiers in Cardiovascular Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0640","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/s12933-020-01158-6","article-title":"Depression and cardiovascular risk-association among Beck depression inventory, PCSK9 levels and insulin resistance","volume":"19","author":"Macchi","year":"2020","journal-title":"Cardiovascular Diabetology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0645","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1093\/eurheartj\/ehz455","article-title":"2019 ESC\/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk","volume":"41","author":"Mach","year":"2020","journal-title":"European Heart Journal"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0650","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1016\/j.jacl.2018.05.012","article-title":"PCSK9 and neurocognitive function: Should it be still an issue after FOURIER and EBBINGHAUS results?","volume":"12","author":"Mannarino","year":"2018","journal-title":"Journal of Clinical Lipidology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0655","doi-asserted-by":"crossref","DOI":"10.1016\/j.metabol.2022.155291","article-title":"Pancreatic PCSK9 controls the organization of the \u03b2-cell secretory pathway via LDLR-cholesterol axis","volume":"136","author":"Marku","year":"2022","journal-title":"Metabolism"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0660","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/cge.13250","article-title":"Single, short in-del, and copy number variations detection in monogenic dyslipidemia using a next-generation sequencing strategy","volume":"94","author":"Marmontel","year":"2018","journal-title":"Clinical Genetics"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0665","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1111\/febs.12721","article-title":"LDL receptor\/lipoprotein recognition: Endosomal weakening of ApoB and ApoE binding to the convex face of the LR5 repeat","volume":"281","author":"Mart\u00ednez-Oliv\u00e1n","year":"2014","journal-title":"The FEBS Journal"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0670","doi-asserted-by":"crossref","first-page":"7100","DOI":"10.1073\/pnas.0402133101","article-title":"Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype","volume":"101","author":"Maxwell","year":"2004","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0675","doi-asserted-by":"crossref","first-page":"31791","DOI":"10.1074\/jbc.M805971200","article-title":"Annexin A2 is a C-terminal PCSK9-binding protein that regulates endogenous low density lipoprotein receptor levels","volume":"283","author":"Mayer","year":"2008","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0680","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1373\/clinchem.2011.165191","article-title":"Novel loss-of-function PCSK9 variant is associated with low plasma LDL cholesterol in a French-Canadian family and with impaired processing and secretion in cell culture","volume":"57","author":"Mayne","year":"2011","journal-title":"Clinical Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0685","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/1476-511X-12-70","article-title":"Differential effects of PCSK9 loss of function variants on serum lipid and PCSK9 levels in Caucasian and African Canadian populations","volume":"12","author":"Mayne","year":"2013","journal-title":"Lipids in Health and Disease"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0690","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1016\/j.jacc.2012.03.007","article-title":"Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin\/kexin type 9 serine protease, SAR236553\/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy","volume":"59","author":"McKenney","year":"2012","journal-title":"Journal of the American College of Cardiology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0695","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1161\/CIRCULATIONAHA.117.029785","article-title":"PCSK9 variants, low-density lipoprotein cholesterol, and neurocognitive impairment: Reasons for geographic and racial differences in stroke study (REGARDS)","volume":"137","author":"Mefford","year":"2018","journal-title":"Circulation"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0700","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1111\/febs.15036","article-title":"Functional analysis of natural PCSK9 mutants in modern and archaic humans","volume":"287","author":"Mikaeeli","year":"2020","journal-title":"The FEBS Journal"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0705","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.atherosclerosis.2006.12.035","article-title":"Genetic variants in PCSK9 in the Japanese population: Rare genetic variants in PCSK9 might collectively contribute to plasma LDL cholesterol levels in the general population","volume":"196","author":"Miyake","year":"2008","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0710","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1016\/j.kint.2020.06.045","article-title":"Secretion of the epithelial sodium channel chaperone PCSK9 from the cortical collecting duct links sodium retention with hypercholesterolemia in nephrotic syndrome","volume":"98","author":"Molina-Jijon","year":"2020","journal-title":"Kidney International"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0715","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.5114\/aoms\/133885","article-title":"PCSK9 immunization using nanoliposomes: Preventive efficacy against hypercholesterolemia and atherosclerosis","volume":"17","author":"Momtazi-Borojeni","year":"2021","journal-title":"Archives of Medical Science"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0720","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1056\/NEJMra1112570","article-title":"A tale of coronary artery disease and myocardial infarction","volume":"366","author":"Nabel","year":"2012","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0725","doi-asserted-by":"crossref","first-page":"40","DOI":"10.7326\/M14-2957","article-title":"Effects of proprotein convertase Subtilisin\/Kexin type 9 antibodies in adults with hypercholesterolemia: A systematic review and meta-analysis","volume":"163","author":"Navarese","year":"2015","journal-title":"Annals of Internal Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0730","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.ijcard.2016.10.084","article-title":"Association of PCSK9 with platelet reactivity in patients with acute coronary syndrome treated with prasugrel or ticagrelor: The PCSK9-REACT study","volume":"227","author":"Navarese","year":"2017","journal-title":"International Journal of Cardiology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0735","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1194\/jlr.M011445","article-title":"A PCSK9-binding antibody that structurally mimics the EGF(A) domain of LDL-receptor reduces LDL cholesterol in vivo","volume":"52","author":"Ni","year":"2011","journal-title":"Journal of Lipid Research"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0740","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.atherosclerosis.2009.11.018","article-title":"The E32K variant of PCSK9 exacerbates the phenotype of familial hypercholesterolaemia by increasing PCSK9 function and concentration in the circulation","volume":"210","author":"Noguchi","year":"2010","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0745","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/1471-2350-15-70","article-title":"Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing: A population-based study","volume":"15","author":"Norsworthy","year":"2014","journal-title":"BMC Medical Genetics"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0750","doi-asserted-by":"crossref","first-page":"3957","DOI":"10.1038\/s41467-018-06467-9","article-title":"A Mendelian randomization study of the effects of blood lipids on breast cancer risk","volume":"9","author":"Nowak","year":"2018","journal-title":"Nature Communications"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0755","doi-asserted-by":"crossref","first-page":"848","DOI":"10.5551\/jat.33407","article-title":"Effects of statin therapy on plasma proprotein convertase Subtilisin\/kexin type 9 and sortilin levels in statin-naive patients with coronary artery disease","volume":"23","author":"Nozue","year":"2016","journal-title":"Journal of Atherosclerosis and Thrombosis"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0760","doi-asserted-by":"crossref","DOI":"10.3390\/ijms232012192","article-title":"PCSK9 affects astrocyte cholesterol metabolism and reduces neuron cholesterol supplying in vitro: Potential implications in Alzheimer\u2019s disease","volume":"23","author":"Papotti","year":"2022","journal-title":"International Journal of Molecular Sciences"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0765","doi-asserted-by":"crossref","first-page":"1084633","DOI":"10.3389\/fnmol.2022.1084633","article-title":"PCSK9 deficiency alters brain lipid composition without affecting brain development and function","volume":"15","author":"P\u00e4rn","year":"2022","journal-title":"Frontiers in Molecular Neuroscience"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0770","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1161\/ATVBAHA.110.214130","article-title":"Circulating proprotein convertase subtilisin kexin type 9 has a diurnal rhythm synchronous with cholesterol synthesis and is reduced by fasting in humans","volume":"30","author":"Persson","year":"2010","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0775","article-title":"Substantial PCSK9 inactivation in \u03b2-cells does not modify glucose homeostasis or insulin secretion in mice","volume":"1866","author":"Peyot","year":"2021","journal-title":"Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0780","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0220254","article-title":"Proprotein convertase subtilisin\/kexin type 9 (PCSK9) in Alzheimer's disease: A genetic and proteomic multi-cohort study","volume":"14","author":"Picard","year":"2019","journal-title":"PLoS One"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0785","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.str.2007.04.004","article-title":"The crystal structure of PCSK9: A regulator of plasma LDL-cholesterol","volume":"15","author":"Piper","year":"2007","journal-title":"Structure"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0790","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.atherosclerosis.2005.08.015","article-title":"Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia","volume":"186","author":"Pisciotta","year":"2006","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0795","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1074\/jbc.M708098200","article-title":"The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2","volume":"283","author":"Poirier","year":"2008","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0800","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1111\/j.1471-4159.2006.03928.x","article-title":"Implication of the proprotein convertase NARC-1\/PCSK9 in the development of the nervous system","volume":"98","author":"Poirier","year":"2006","journal-title":"Journal of Neurochemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0805","series-title":"Developmental transcriptome","volume":"vol. 2023","author":"Portal","year":"2023"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0810","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1001\/jamacardio.2018.4178","article-title":"Interindividual variation in low-density lipoprotein cholesterol level reduction with evolocumab: An analysis of FOURIER trial data","volume":"4","author":"Qamar","year":"2019","journal-title":"JAMA Cardiology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0815","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.112.000028","article-title":"Elevated PCSK9 levels in untreated patients with heterozygous or homozygous familial hypercholesterolemia and the response to high-dose statin therapy","volume":"2","author":"Raal","year":"2013","journal-title":"Journal of the American Heart Association"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0820","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1056\/NEJMoa1913805","article-title":"Inclisiran for the treatment of heterozygous familial hypercholesterolemia","volume":"382","author":"Raal","year":"2020","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0825","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.atherosclerosis.2021.03.044","article-title":"Effects of proprotein convertase subtilisin kexin type 9 modulation in human pancreatic beta cells function","volume":"326","author":"Ramin-Mangata","year":"2021","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0830","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1111\/joim.12946","article-title":"Reduced plasma PCSK9 response in patients with bacteraemia is associated with mortality","volume":"286","author":"Rannikko","year":"2019","journal-title":"Journal of Internal Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0835","doi-asserted-by":"crossref","first-page":"5374","DOI":"10.1073\/pnas.0501652102","article-title":"Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9","volume":"102","author":"Rashid","year":"2005","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0840","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1056\/NEJMoa1615758","article-title":"Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol","volume":"376","author":"Ray","year":"2017","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0845","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1056\/NEJMoa1912387","article-title":"Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol","volume":"382","author":"Ray","year":"2020","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0850","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1056\/NEJMoa1701488","article-title":"Cardiovascular efficacy and safety of bococizumab in high-risk patients","volume":"376","author":"Ridker","year":"2017","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0855","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1093\/eurheartj\/ehv568","article-title":"Plasma proprotein convertase subtilisin\/kexin type 9 levels and the risk of first cardiovascular events","volume":"37","author":"Ridker","year":"2016","journal-title":"European Heart Journal"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0860","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1056\/NEJMoa1501031","article-title":"Efficacy and safety of alirocumab in reducing lipids and cardiovascular events","volume":"372","author":"Robinson","year":"2015","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0865","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1126\/science.1078124","article-title":"Structure of the LDL receptor extracellular domain at endosomal pH","volume":"298","author":"Rudenko","year":"2002","journal-title":"Science"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0870","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMoa1615664","article-title":"Evolocumab and clinical outcomes in patients with cardiovascular disease","volume":"376","author":"Sabatine","year":"2017","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0875","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1056\/NEJMoa1500858","article-title":"Efficacy and safety of evolocumab in reducing lipids and cardiovascular events","volume":"372","author":"Sabatine","year":"2015","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0880","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/S2213-8587(17)30313-3","article-title":"Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: A prespecified analysis of the FOURIER randomised controlled trial","volume":"5","author":"Sabatine","year":"2017","journal-title":"The Lancet Diabetes and Endocrinology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0885","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1111\/dom.12536","article-title":"Effect of statin therapy on plasma proprotein convertase subtilisin kexin 9 (PCSK9) concentrations: A systematic review and meta-analysis of clinical trials","volume":"17","author":"Sahebkar","year":"2015","journal-title":"Diabetes, Obesity & Metabolism"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0890","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2022.102096","article-title":"Proprotein convertase PCSK9 affects expression of key surface proteins in human pancreatic beta cells via intracellular and extracellular regulatory circuits","volume":"298","author":"Saitoski","year":"2022","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0895","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1074\/jbc.RA119.010221","article-title":"A transient amphipathic helix in the prodomain of PCSK9 facilitates binding to low-density lipoprotein particles","volume":"295","author":"Sarkar","year":"2020","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0900","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S2213-8587(16)30396-5","article-title":"PCSK9 genetic variants and risk of type 2 diabetes: A mendelian randomisation study","volume":"5","author":"Schmidt","year":"2017","journal-title":"The Lancet Diabetes and Endocrinology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0905","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1194\/jlr.M061903","article-title":"Proteolytic cleavage of antigen extends the durability of an anti-PCSK9 monoclonal antibody","volume":"56","author":"Schroeder","year":"2015","journal-title":"Journal of Lipid Research"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0910","doi-asserted-by":"crossref","first-page":"11079","DOI":"10.1038\/s41598-019-47242-0","article-title":"Anti-PCSK9 antibodies inhibit pro-atherogenic mechanisms in APOE*3Leiden.CETP mice","volume":"9","author":"Schuster","year":"2019","journal-title":"Scientific Reports"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0915","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1073\/pnas.0335507100","article-title":"The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): Liver regeneration and neuronal differentiation","volume":"100","author":"Seidah","year":"2003","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0920","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/nrd3699","article-title":"The biology and therapeutic targeting of the proprotein convertases","volume":"11","author":"Seidah","year":"2012","journal-title":"Nature Reviews. Drug Discovery"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0925","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1210\/endrev\/bnab035","article-title":"The multifaceted biology of PCSK9","volume":"43","author":"Seidah","year":"2022","journal-title":"Endocrine Reviews"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0930","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.atherosclerosis.2016.10.028","article-title":"Spectrum of mutations in homozygous familial hypercholesterolemia in India, with four novel mutations","volume":"255","author":"Setia","year":"2016","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0935","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1161\/CIRCRESAHA.118.311227","article-title":"Pcsk9","volume":"122","author":"Shapiro","year":"2018","journal-title":"Circulation Research"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0940","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1681\/ASN.2020091376","article-title":"Hypercholesterolemia in progressive renal failure is associated with changes in hepatic heparan sulfate - PCSK9 interaction","volume":"32","author":"Shrestha","year":"2021","journal-title":"Journal of the American Society of Nephrology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0945","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.atherosclerosis.2012.02.018","article-title":"Effect of mutations in LDLR and PCSK9 genes on phenotypic variability in Tunisian familial hypercholesterolemia patients","volume":"222","author":"Slimani","year":"2012","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0950","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0140-6736(12)60771-5","volume":"380","author":"Stein","year":"2012","journal-title":"Lancet"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0955","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1056\/NEJMoa1105803","article-title":"Effect of a monoclonal antibody to PCSK9 on LDL cholesterol","volume":"366","author":"Stein","year":"2012","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0960","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00439-013-1358-4","article-title":"The human gene mutation database: Building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine","volume":"133","author":"Stenson","year":"2014","journal-title":"Human Genetics"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0965","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1126\/science.2988123","article-title":"The LDL receptor gene: A mosaic of exons shared with different proteins","volume":"228","author":"S\u00fcdhof","year":"1985","journal-title":"Science"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0970","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1593\/neo.121252","article-title":"Proprotein convertase subtilisin\/kexin type 9 deficiency reduces melanoma metastasis in liver","volume":"14","author":"Sun","year":"2012","journal-title":"Neoplasia"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0975","doi-asserted-by":"crossref","first-page":"8107","DOI":"10.1038\/s41598-018-26453-x","article-title":"Blood lipid-related low-frequency variants in LDLR and PCSK9 are associated with onset age and risk of myocardial infarction in Japanese","volume":"8","author":"Tajima","year":"2018","journal-title":"Scientific Reports"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0980","doi-asserted-by":"crossref","first-page":"8246","DOI":"10.1074\/jbc.M610137200","article-title":"Crystal structure of unautoprocessed precursor of subtilisin from a hyperthermophilic archaeon: Evidence for Ca2+\u2212induced folding","volume":"282","author":"Tanaka","year":"2007","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0985","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1161\/CIRCULATIONAHA.113.001592","article-title":"Serum proprotein convertase subtilisin\/kexin type 9 and cell surface low-density lipoprotein receptor: Evidence for a reciprocal regulation","volume":"127","author":"Tavori","year":"2013","journal-title":"Circulation"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0990","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s11883-016-0604-3","article-title":"Statins and their effect on PCSK9-impact and clinical relevance","volume":"18","author":"Taylor","year":"2016","journal-title":"Current Atherosclerosis Reports"},{"key":"10.1016\/j.pharmthera.2023.108480_bb0995","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s00439-003-1071-9","article-title":"A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree","volume":"114","author":"Timms","year":"2004","journal-title":"Human Genetics"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1000","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/j.kint.2017.12.011","article-title":"Efficacy and safety of lipid lowering by alirocumab in chronic kidney disease","volume":"93","author":"Toth","year":"2018","journal-title":"Kidney International"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1005","doi-asserted-by":"crossref","first-page":"41","DOI":"10.2174\/1874192401105010041","article-title":"Dyslipidemia associated with chronic kidney disease","volume":"5","author":"Tsimihodimos","year":"2011","journal-title":"Open Cardiovascular Medicine Journal"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1010","doi-asserted-by":"crossref","first-page":"16770","DOI":"10.1021\/acs.jmedchem.1c01599","article-title":"A series of novel, highly potent, and orally bioavailable next-generation tricyclic peptide PCSK9 inhibitors","volume":"64","author":"Tucker","year":"2021","journal-title":"Journal of Medicinal Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1015","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue-based map of the human proteome","volume":"347","author":"Uhl\u00e9n","year":"2015","journal-title":"Science"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1020","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.jmb.2018.11.025","article-title":"Identification of a helical segment within the intrinsically disordered region of the PCSK9 prodomain","volume":"431","author":"Ultsch","year":"2019","journal-title":"Journal of Molecular Biology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1025","series-title":"Evolocumab for PCSK9 lowering in early acute sepsis (the PLEASe study)","author":"University of British Columbia","year":"2021"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1030","series-title":"A randomized trial assessing the effects of inclisiran on clinical outcomes among people with cardiovascular disease","author":"University of Oxford, T. T. S. G","year":"2023"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1035","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.atherosclerosis.2011.06.006","article-title":"Mutational analysis of the LDL receptor and APOB genes in Mexican individuals with autosomal dominant hypercholesterolemia","volume":"218","author":"Vaca","year":"2011","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1040","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1086\/302370","article-title":"A third major locus for autosomal dominant hypercholesterolemia maps to 1p34.1-p32","volume":"64","author":"Varret","year":"1999","journal-title":"American Journal of Human Genetics"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1045","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/joim.13150","article-title":"PCSK9 is associated with mortality in patients with septic shock: Data from the ALBIOS study","volume":"289","author":"Vecchi\u00e9","year":"2021","journal-title":"Journal of Internal Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1050","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1038\/s41587-022-01445-5","volume":"40","author":"Verve takes base editors into humans","year":"2022","journal-title":"Nature Biotechnology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1055","series-title":"A study of VERVE-101 in patients with familial hypercholesterolemia and cardiovascular disease","author":"Verve Therapeutics, I","year":"2024"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1060","doi-asserted-by":"crossref","first-page":"258ra143","DOI":"10.1126\/scitranslmed.3008782","article-title":"PCSK9 is a critical regulator of the innate immune response and septic shock outcome","volume":"6","author":"Walley","year":"2014","journal-title":"Science Translational Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1065","doi-asserted-by":"crossref","first-page":"14360","DOI":"10.1038\/s41598-017-14307-x","article-title":"Proprotein convertase subtilisin\/kexin type 9 (PCSK9) deficiency is protective against venous thrombosis in mice","volume":"7","author":"Wang","year":"2017","journal-title":"Scientific Reports"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1070","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12944-018-0680-1","article-title":"Complex genetic architecture in severe hypobetalipoproteinemia","volume":"17","author":"Wang","year":"2018","journal-title":"Lipids in Health and Disease"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1075","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1194\/jlr.M028563","article-title":"Molecular characterization of proprotein convertase subtilisin\/kexin type 9-mediated degradation of the LDLR","volume":"53","author":"Wang","year":"2012","journal-title":"Journal of Lipid Research"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1080","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1111\/j.1525-1497.2004.40049.x","article-title":"Managing dyslipidemia in chronic kidney disease","volume":"19","author":"Weiner","year":"2004","journal-title":"Journal of General Internal Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1085","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1194\/jlr.P055699","article-title":"Global molecular analysis and APOE mutations in a cohort of autosomal dominant hypercholesterolemia patients in France","volume":"57","author":"Wintjens","year":"2016","journal-title":"Journal of Lipid Research"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1090","series-title":"Treatment of severe infection with antihyperlipidemia drug","author":"Wolfson Medical Center, A.-H. M. C","year":"2021"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1095","doi-asserted-by":"crossref","DOI":"10.3389\/fcvm.2021.764038","article-title":"Regulation of PCSK9 expression and function: Mechanisms and therapeutic implications","volume":"8","author":"Xia","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1100","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.atherosclerosis.2017.02.007","article-title":"The genetic spectrum of familial hypercholesterolemia in the central south region of China","volume":"258","author":"Xiang","year":"2017","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1105","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.ijcard.2016.04.103","article-title":"Association between plasma PCSK9 levels and 10-year progression of carotid atherosclerosis beyond LDL-C: A cohort study","volume":"215","author":"Xie","year":"2016","journal-title":"International Journal of Cardiology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1110","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1007\/s13238-021-00821-2","article-title":"Potentiating CD8(+) T cell antitumor activity by inhibiting PCSK9 to promote LDLR-mediated TCR recycling and signaling","volume":"12","author":"Yuan","year":"2021","journal-title":"Protein & Cell"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1115","doi-asserted-by":"crossref","first-page":"2687692","DOI":"10.1155\/2020\/2687692","article-title":"PCSK9: A potential therapeutic target for sepsis","volume":"2020","author":"Yuan","year":"2020","journal-title":"Journal of Immunology Research"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1120","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1056\/NEJMoa1600176","article-title":"Cholesterol lowering in intermediate-risk persons without cardiovascular disease","volume":"374","author":"Yusuf","year":"2016","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1125","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1007\/s00228-021-03149-2","article-title":"A phase I study assessing the safety, tolerability, immunogenicity, and low-density lipoprotein cholesterol-lowering activity of immunotherapeutics targeting PCSK9","volume":"77","author":"Zeitlinger","year":"2021","journal-title":"European Journal of Clinical Pharmacology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1130","doi-asserted-by":"crossref","first-page":"13045","DOI":"10.1073\/pnas.0806312105","article-title":"Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor","volume":"105","author":"Zhang","year":"2008","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1135","doi-asserted-by":"crossref","first-page":"18602","DOI":"10.1074\/jbc.M702027200","article-title":"Binding of proprotein convertase subtilisin\/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation","volume":"282","author":"Zhang","year":"2007","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1140","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1074\/jbc.M113.514067","article-title":"Identification of a small peptide that inhibits PCSK9 protein binding to the low density lipoprotein receptor","volume":"289","author":"Zhang","year":"2014","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1145","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/nsmb.3453","article-title":"Discovery of a cryptic peptide-binding site on PCSK9 and design of antagonists","volume":"24","author":"Zhang","year":"2017","journal-title":"Nature Structural & Molecular Biology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1150","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1086\/507488","article-title":"Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote","volume":"79","author":"Zhao","year":"2006","journal-title":"American Journal of Human Genetics"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1155","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1161\/ATVBAHA.115.306172","article-title":"Association of proprotein convertase Subtilisin\/Kexin type 9 (PCSK9) with cardiovascular risk in primary prevention","volume":"35","author":"Zhu","year":"2015","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"10.1016\/j.pharmthera.2023.108480_bb1160","doi-asserted-by":"crossref","first-page":"315","DOI":"10.3233\/JAD-160411","article-title":"Increased PCSK9 cerebrospinal fluid concentrations in Alzheimer\u2019s disease","volume":"55","author":"Zimetti","year":"2017","journal-title":"Journal of Alzheimer\u2019s Disease"}],"container-title":["Pharmacology & Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0163725823001444?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0163725823001444?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T22:33:42Z","timestamp":1759012422000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0163725823001444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9]]},"references-count":230,"alternative-id":["S0163725823001444"],"URL":"https:\/\/doi.org\/10.1016\/j.pharmthera.2023.108480","relation":{},"ISSN":["0163-7258"],"issn-type":[{"value":"0163-7258","type":"print"}],"subject":[],"published":{"date-parts":[[2023,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Targeting PCSK9 to tackle cardiovascular disease","name":"articletitle","label":"Article Title"},{"value":"Pharmacology & Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.pharmthera.2023.108480","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"108480"}}