{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:13:05Z","timestamp":1793833985117,"version":"4.6.1"},"reference-count":128,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012542","name":"Sichuan Province Science and Technology Support Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Atherosclerosis is an early pathological basis of numerous cardiovascular events that result in death or disability. Recent studies have described PCSK9 as a novel target for the treatment of atherosclerosis; PCSK9 is capable of degrading LDLR on the surface of hepatocytes through the regulation of lipid metabolism, and it can function as a novel inflammatory modulator in atherosclerosis. Inflammasomes are important intracellular multiprotein complexes that promote the inflammatory response in atherosclerosis. Among inflammasomes, the NLRP3 inflammasome is particularly notable because of its important role in the development of atherosclerotic disease. After activation, NLRP3 forms a complex with ASC and pro-caspase-1, converting pro-caspase-1 into activated caspase-1, which may trigger the release of IL-1\u03b2 and IL-18 and contribute to the inflammatory response. Several recent studies have indicated that there may be interactions between PCSK9 and the NLRP3 inflammasome, which may contribute to the inflammatory response that drives atherosclerosis development and progression. On the one hand, the NLRP3 inflammasome plays an important role <jats:italic>via<\/jats:italic> IL-1\u03b2 in regulating PCSK9 secretion. On the other hand, PCSK9 regulates caspase-1-dependent pyroptosis by initiating mtDNA damage and activating NLRP3 inflammasome signaling. This paper reviews the mechanisms underlying PCSK9 and NLRP3 inflammasome activation in the context of atherosclerosis. Furthermore, we describe the current understanding of the specific molecular mechanism underlying the interactions between PCSK9 and NLRP3 inflammasome signaling as well as the drug repositioning events that influence vascular cells and exert beneficial antiatherosclerotic effects. This review may provide a new therapeutic direction for the effective prevention and treatment of atherosclerosis in the clinic.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1126823","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T08:53:21Z","timestamp":1677056001000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":35,"title":["Interactions between PCSK9 and NLRP3 inflammasome signaling in atherosclerosis"],"prefix":"10.3389","volume":"14","author":[{"given":"Yanan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinzhi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingcan","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbo","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2016.185","article-title":"Inflammatory processes in cardiovascular disease: A route to targeted therapies","volume":"14","author":"Ruparelia","year":"2017","journal-title":"Nat Rev Cardiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2034","DOI":"10.3390\/ijms18102034","article-title":"New insights into the role of inflammation in the pathogenesis of atherosclerosis","volume":"18","author":"Wu","year":"2017","journal-title":"Int J Mol Sci"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvx253","article-title":"Endothelial-mesenchymal transition in atherosclerosis","volume":"114","author":"Souilhol","year":"2018","journal-title":"Cardiovasc Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1210\/er.2018-00184","article-title":"The forgotten lipids: Triglycerides, remnant cholesterol, and atherosclerotic cardiovascular disease risk","volume":"40","author":"Sandesara","year":"2019","journal-title":"Endocr Rev"},{"key":"B5","doi-asserted-by":"publisher","first-page":"5880","DOI":"10.3390\/ijms22115880","article-title":"Pcsk9 biology and its role in atherothrombosis","volume":"22","author":"Barale","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.037085","article-title":"Dissection of the endogenous cellular pathways of Pcsk9-induced low density lipoprotein receptor degradation: Evidence for an intracellular route","volume":"284","author":"Poirier","year":"2009","journal-title":"J Biol Chem"},{"key":"B7","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1038\/s41574-018-0110-5","article-title":"Inhibiting Pcsk9 - biology beyond ldl control","volume":"15","author":"Stoekenbroek","year":"2018","journal-title":"Nat Rev Endocrinol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvw053","article-title":"Human Pcsk9 promotes hepatic lipogenesis and atherosclerosis development Via apoe- and ldlr-mediated mechanisms","volume":"110","author":"Tavori","year":"2016","journal-title":"Cardiovasc Res"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/path.915","article-title":"Spontaneous plaque rupture and secondary thrombosis in apolipoprotein e-deficient and ldl receptor-deficient mice","volume":"195","author":"Calara","year":"2001","journal-title":"J Pathol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2015.95","article-title":"Molecular mechanisms regulating Nlrp3 inflammasome activation","volume":"13","author":"Jo","year":"2016","journal-title":"Cell Mol Immunol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.jacbts.2021.08.006","article-title":"Targeting the inflammasome in cardiovascular disease","volume":"7","author":"Olsen","year":"2022","journal-title":"JACC Bas Transl Sci"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.311362","article-title":"Nlrp3 inflammasome and the il-1 pathway in atherosclerosis","volume":"122","author":"Grebe","year":"2018","journal-title":"Circ Res"},{"key":"B13","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1007\/s00395-020-00832-w","article-title":"Pcsk9 regulates pyroptosis Via mtdna damage in chronic myocardial ischemia","volume":"115","author":"Wang","year":"2020","journal-title":"Bas Res In Cardiol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-022-01715-z","article-title":"Pcsk9 promotes endothelial dysfunction during sepsis via the Tlr4\/Myd88\/Nf-Kb and Nlrp3 pathways","author":"Huang","year":"2022","journal-title":"Inflammation"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.894789","article-title":"Targeting Pcsk9 ameliorates graft vascular disease in mice by inhibiting Nlrp3 inflammasome activation in vascular smooth muscle cells","volume":"13","author":"Zou","year":"2022","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.7150\/thno.45939","article-title":"Nlrp3 inflammasome il-1\u03b2 regulates Pcsk9 secretion","volume":"10","author":"Ding","year":"2020","journal-title":"Theranostics"},{"key":"B17","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1111\/j.1365-2141.1977.tb01022.x","article-title":"Cytochemical profile of human haematopoietic biopsy cells and derived cell lines","volume":"37","author":"Sundstr\u00f6m","year":"1977","journal-title":"Br J Haematol"},{"key":"B18","doi-asserted-by":"publisher","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":"Proc Natl Acad Sci U.S.A."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2021.100096","article-title":"Pcsk9 is not secreted from mature differentiated intestinal cells","volume":"62","author":"Moreau","year":"2021","journal-title":"J Lipid Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.2174\/1389557518666180423111442","article-title":"Pcsk9 inhibitors: Novel therapeutic strategies for lowering ldlcholesterol","volume":"19","author":"Wang","year":"2019","journal-title":"Mini Rev Med Chem"},{"key":"B21","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.biopha.2018.05.024","article-title":"Role of Pcsk9 in lipid metabolism and atherosclerosis","volume":"104","author":"Lin","year":"2018","journal-title":"Biomed Pharmacother = Biomed Pharmacother"},{"key":"B22","doi-asserted-by":"publisher","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":"J Pathol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvv178","article-title":"Cross-talk between lox-1 and Pcsk9 in vascular tissues","volume":"107","author":"Ding","year":"2015","journal-title":"Cardiovasc Res"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.21037\/atm-22-4652","article-title":"Pcsk9 inhibitor inclisiran for treating atherosclerosis Via regulation of endothelial cell pyroptosis","volume":"10","author":"Kong","year":"2022","journal-title":"Ann Transl Med"},{"key":"B25","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3892\/ijmm.2021.4886","article-title":"Pcsk9 mediates the oxidative Low\u2212Density Lipoprotein\u2212Induced pyroptosis of vascular endothelial cells Via the Uqcrc1\/Ros pathway","volume":"47","author":"Zeng","year":"2021","journal-title":"Int J Mol Med"},{"key":"B26","doi-asserted-by":"publisher","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":"Sci Rep"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2011.11.026","article-title":"Proprotein convertase subtilisin kexin type 9 (Pcsk9) secreted by cultured smooth muscle cells reduces macrophages ldlr levels","volume":"220","author":"Ferri","year":"2012","journal-title":"Atherosclerosis"},{"key":"B28","doi-asserted-by":"publisher","first-page":"2267","DOI":"10.1038\/s41598-018-20425-x","article-title":"Pcsk9 induces a pro-inflammatory response in macrophages","volume":"8","author":"Ricci","year":"2018","journal-title":"Sci Rep"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.atherosclerosis.2016.11.019","article-title":"Inhibitory effect of Pcsk9 on Abca1 protein expression and cholesterol efflux in macrophages","volume":"256","author":"Adorni","year":"2017","journal-title":"Atherosclerosis"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2021.746989","article-title":"Role of Pcsk9 in homocysteine-accelerated lipid accumulation in macrophages and atherosclerosis in apoe mice","volume":"8","author":"Jin","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"e13459","DOI":"10.1111\/eci.13459","article-title":"Pcsk9 and atherosclerosis: Looking beyond ldl regulation","volume":"51","author":"Ragusa","year":"2021","journal-title":"Eur J Clin Invest"},{"key":"B32","doi-asserted-by":"publisher","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":"B33","doi-asserted-by":"publisher","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":"Cardiovasc Res"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvaa254","article-title":"Pcsk9 and Lrp5 in macrophage lipid internalization and inflammation","volume":"117","author":"Badimon","year":"2021","journal-title":"Cardiovasc Res"},{"key":"B35","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.atherosclerosis.2013.01.023","article-title":"Pcsk9 plays a significant role in cholesterol homeostasis and lipid transport in intestinal epithelial cells","volume":"227","author":"Levy","year":"2013","journal-title":"Atherosclerosis"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2017.04.023","article-title":"New role of Pcsk9 in atherosclerotic inflammation promotion involving the Tlr4\/Nf-Kb pathway","volume":"262","author":"Tang","year":"2017","journal-title":"Atherosclerosis"},{"key":"B37","doi-asserted-by":"publisher","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":"J Biol Chem"},{"key":"B38","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1161\/CIRCRESAHA.115.306361","article-title":"Vascular smooth muscle cells in atherosclerosis","volume":"118","author":"Bennett","year":"2016","journal-title":"Circ Res"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2016.07.910","article-title":"Pcsk9 knock-out mice are protected from neointimal formation in response to perivascular carotid collar placement","volume":"253","author":"Ferri","year":"2016","journal-title":"Atherosclerosis"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2014.6054","article-title":"Hemodynamic shear stress Via ros modulates Pcsk9 expression in human vascular endothelial and smooth muscle cells and along the mouse aorta","volume":"22","author":"Ding","year":"2015","journal-title":"Antioxid Redox Signal"},{"key":"B41","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s00418-016-1408-9","article-title":"Impaired Sirt1 promotes the migration of vascular smooth muscle cell-derived foam cells","volume":"146","author":"Zhang","year":"2016","journal-title":"Histochem Cell Biol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"997-1008","DOI":"10.1089\/ars.2016.6631","article-title":"Cross-talk between Pcsk9 and damaged mtdna in vascular smooth muscle cells: Role in apoptosis","volume":"25","author":"Ding","year":"2016","journal-title":"Antioxid Redox Signal"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2017.12.027","article-title":"The Nlrp3 inflammasome and the emerging role of colchicine to inhibit atherosclerosis-associated inflammation","volume":"269","author":"Mart\u00ednez","year":"2018","journal-title":"Atherosclerosis"},{"key":"B44","doi-asserted-by":"publisher","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":"Eur Heart J"},{"key":"B45","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1111\/apha.12725","article-title":"Effects of shear stress on endothelial cells: Go with the flow","volume":"219","author":"Chistiakov","year":"2017","journal-title":"Acta Physiol (Oxf)"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvz313","article-title":"Pcsk9 and inflammation: Role of shear stress, pro-inflammatory cytokines, and lox-1","volume":"116","author":"Ding","year":"2020","journal-title":"Cardiovasc Res"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern recognition receptors and inflammation","volume":"140","author":"Takeuchi","year":"2010","journal-title":"Cell"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032414-112240","article-title":"Innate immune pattern recognition: A cell biological perspective","volume":"33","author":"Brubaker","year":"2015","journal-title":"Annu Rev Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02305","article-title":"Regulation of Nlrp3 inflammasome by phosphorylation","volume":"9","author":"Song","year":"2018","journal-title":"Front In Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02538","article-title":"Pharmacological inhibitors of the Nlrp3 inflammasome","volume":"10","author":"Zahid","year":"2019","journal-title":"Front In Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.315937","article-title":"Interleukin-1 and the inflammasome as therapeutic targets in cardiovascular disease","volume":"126","author":"Abbate","year":"2020","journal-title":"Circ Res"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)00384-4","article-title":"Asc, which is composed of a pyd and a card, is up-regulated by inflammation and apoptosis in human neutrophils","volume":"293","author":"Shiohara","year":"2002","journal-title":"Biochem Biophys Res Commun"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20172222","article-title":"Caspase-1 self-cleavage is an intrinsic mechanism to terminate inflammasome activity","volume":"215","author":"Boucher","year":"2018","journal-title":"J Exp Med"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6687555","article-title":"Tlr4-Nlrp3-Gsdmd-Mediated pyroptosis plays an important role in aggravated liver injury of Cd38 sepsis mice","volume":"2021","author":"Zhang","year":"2021","journal-title":"J Immunol Res"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062426","article-title":"Pepsin digest of wheat gliadin fraction increases production of il-1\u03b2 Via Tlr4\/Myd88\/Trif\/Mapk\/Nf-Kb signaling pathway and an Nlrp3 inflammasome activation","volume":"8","author":"Palov\u00e1-Jel\u00ednkov\u00e1","year":"2013","journal-title":"PloS One"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.02.008","article-title":"Unified polymerization mechanism for the assembly of asc-dependent inflammasomes","volume":"156","author":"Lu","year":"2014","journal-title":"Cell"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4402194","article-title":"The pyroptosome: A supramolecular assembly of asc dimers mediating inflammatory cell death Via caspase-1 activation","volume":"14","author":"Fernandes-Alnemri","year":"2007","journal-title":"Cell Death Different"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.4.110807.092239","article-title":"Nod-like receptors: Role in innate immunity and inflammatory disease","volume":"4","author":"Chen","year":"2009","journal-title":"Annu Rev Pathol"},{"key":"B59","doi-asserted-by":"publisher","first-page":"941-955.e20","DOI":"10.1016\/j.cell.2020.02.002","article-title":"Structural mechanism for gsdmd targeting by autoprocessed caspases in pyroptosis","volume":"180","author":"Wang","year":"2020","journal-title":"Cell"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abj3859","article-title":"Nlrp3 inflammasome activation triggers gasdermin d-independent inflammation","volume":"6","author":"Wang","year":"2021","journal-title":"Sci Immunol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.652963","article-title":"Pyroptosis in the initiation and progression of atherosclerosis","volume":"12","author":"Qian","year":"2021","journal-title":"Front Pharmacol"},{"key":"B62","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1186\/s12872-019-1263-4","article-title":"Apolipoprotein m and sphingosine-1-Phosphate complex alleviates tnf-A-Induced endothelial cell injury and inflammation through Pi3k\/Akt signaling pathway","volume":"19","author":"Liu","year":"2019","journal-title":"BMC Cardiovasc Disord"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2020.109843","article-title":"Bdnf corrects Nlrp3 inflammasome-induced pyroptosis and glucose metabolism reprogramming through Klf2\/Hk1 pathway in vascular endothelial cells","volume":"78","author":"Jin","year":"2021","journal-title":"Cell Signal"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2020.111847","article-title":"Vx-765 attenuates atherosclerosis in apoe deficient mice by modulating vsmcs pyroptosis","volume":"389","author":"Li","year":"2020","journal-title":"Exp Cell Res"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2013.01.211","article-title":"Nalp3 inflammasome is activated and required for vascular smooth muscle cell calcification","volume":"168","author":"Wen","year":"2013","journal-title":"Int J Cardiol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.31.19569","article-title":"Ligation of Cd40 activates interleukin 1beta-converting enzyme (Caspase-1) activity in vascular smooth muscle and endothelial cells and promotes elaboration of active interleukin 1beta","volume":"272","author":"Sch\u00f6nbeck","year":"1997","journal-title":"J Biol Chem"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10431","article-title":"Expression of interleukin-1 beta and interleukin-1 receptor antagonist in oxldl-treated human aortic smooth muscle cells and in the neointima of cholesterol-fed endothelia-denuded rabbits","volume":"88","author":"Lin","year":"2003","journal-title":"J Cell Biochem"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2011.10.013","article-title":"Caspase-1 deficiency decreases atherosclerosis in apolipoprotein e-null mice","volume":"28","author":"Gage","year":"2012","journal-title":"Can J Cardiol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/507208","article-title":"Silence of Nlrp3 suppresses atherosclerosis and stabilizes plaques in apolipoprotein e-deficient mice","volume":"2014","author":"Zheng","year":"2014","journal-title":"Mediators Inflammation"},{"key":"B70","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s00011-013-0667-3","article-title":"Oxldl-induced il-1 beta secretion promoting foam cells formation was mainly Via Cd36 mediated ros production leading to Nlrp3 inflammasome activation","volume":"63","author":"Liu","year":"2014","journal-title":"Inflammation Res"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu114","article-title":"Lox-1, mtdna damage, and Nlrp3 inflammasome activation in macrophages: Implications in atherogenesis","volume":"103","author":"Ding","year":"2014","journal-title":"Cardiovasc Res"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002843","article-title":"Serum amyloid a activates the Nlrp3 inflammasome Via P2x7 receptor and a cathepsin b-sensitive pathway","volume":"186","author":"Niemi","year":"2011","journal-title":"J Immunol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1038\/nature08938","article-title":"Nlrp3 inflammasomes are required for atherogenesis and activated by cholesterol crystals","volume":"464","author":"Duewell","year":"2010","journal-title":"Nature"},{"key":"B74","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1038\/s41590-019-0539-2","article-title":"Endogenous oxidized phospholipids reprogram cellular metabolism and boost hyperinflammation","volume":"21","author":"Di Gioia","year":"2020","journal-title":"Nat Immunol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3109\/08830185.2014.969421","article-title":"Cellular metabolism and macrophage functional polarization","volume":"34","author":"Zhu","year":"2015","journal-title":"Int Rev Immunol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1126\/science.abg3067","article-title":"Olfactory receptor 2 in vascular macrophages drives atherosclerosis by Nlrp3-dependent il-1 production","volume":"375","author":"Orecchioni","year":"2022","journal-title":"Sci (New York NY)"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2107682118","article-title":"Desmosterol suppresses macrophage inflammasome activation and protects against vascular inflammation and atherosclerosis","volume":"118","author":"Zhang","year":"2021","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.16.8.1000","article-title":"Interleukin-1 beta in coronary arteries of patients with ischemic heart disease","volume":"16","author":"Galea","year":"1996","journal-title":"Arteriosclerosis Thrombosis Vasc Biol"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707213","article-title":"P2x receptor characterization and il-1\/Il-1ra release from human endothelial cells","volume":"151","author":"Wilson","year":"2007","journal-title":"Br J Pharmacol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202100695RR","article-title":"Cytotoxin-associated gene a (Caga) promotes aortic endothelial inflammation and accelerates atherosclerosis through the Nlrp3\/Caspase-1\/Il-1\u03b2 axis","volume":"35","author":"Li","year":"2021","journal-title":"FASEB J"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00024.2005","article-title":"Cytokines in atherosclerosis: Pathogenic and regulatory pathways","volume":"86","author":"Tedgui","year":"2006","journal-title":"Physiol Rev"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvab337","article-title":"Interleukin-1\u03b2 suppression dampens inflammatory leucocyte production and uptake in atherosclerosis","volume":"118","author":"Hettwer","year":"2022","journal-title":"Cardiovasc Res"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.208389","article-title":"Vascular smooth muscle cell apoptosis induces interleukin-1-Directed inflammation: Effects of hyperlipidemia-mediated inhibition of phagocytosis","volume":"106","author":"Clarke","year":"2010","journal-title":"Circ Res"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/0013-9351(81)90037-2","article-title":"Analyses of tissue, blood, and urine samples from a baboon gavaged with chrysotile and crocidolite asbestos","volume":"25","author":"Hallenbeck","year":"1981","journal-title":"Environ Res"},{"key":"B85","doi-asserted-by":"publisher","first-page":"340","DOI":"10.3390\/ijms23010340","article-title":"Nlrp3 inflammasome activation controls vascular smooth muscle cells phenotypic switch in atherosclerosis","volume":"23","author":"Burger","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2018.1498118","article-title":"Lipid lowering drugs and inflammatory changes: An impact on cardiovascular outcomes","volume":"50","author":"Ruscica","year":"2018","journal-title":"Ann Med"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1002\/oby.22985","article-title":"White adipose tissue surface expression of ldlr and Cd36 is associated with risk factors for type 2 diabetes in adults with obesity","volume":"28","author":"Cyr","year":"2020","journal-title":"Obes (Silver Spring)"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14721","article-title":"Lower plasma Pcsk9 in normocholesterolemic subjects is associated with upregulated adipose tissue surface-expression of ldlr and Cd36 and Nlrp3 inflammasome","volume":"9","author":"Cyr","year":"2021","journal-title":"Physiol Rep"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.02.085","article-title":"Pcsk9 regulates the chemokine receptor Ccr2 on monocytes","volume":"485","author":"Grune","year":"2017","journal-title":"Biochem Biophys Res Commun"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25930","article-title":"Nlrp3 inflammasome: Its regulation and involvement in atherosclerosis","volume":"233","author":"Hoseini","year":"2018","journal-title":"J Cell Physiol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.4149\/gpb-2019057","article-title":"Pcsk9 promotes the secretion of pro-inflammatory cytokines by macrophages to aggravate H\/R-induced cardiomyocyte injury Via activating nf-Kb signalling","volume":"39","author":"Yang","year":"2020","journal-title":"Gen Physiol Biophys"},{"key":"B92","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1038\/s41419-019-2162-4","article-title":"Pyroptosis is a critical inflammatory pathway in the placenta from early onset preeclampsia and in human trophoblasts exposed to hypoxia and endoplasmic reticulum stressors","volume":"10","author":"Cheng","year":"2019","journal-title":"Cell Death Dis"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvy128","article-title":"Pcsk9 expression in the ischaemic heart and its relationship to infarct size, cardiac function, and development of autophagy","volume":"114","author":"Ding","year":"2018","journal-title":"Cardiovasc Res"},{"key":"B94","doi-asserted-by":"publisher","first-page":"e12563","DOI":"10.1111\/cpr.12563","article-title":"Role of pyroptosis in cardiovascular disease","volume":"52","author":"Zhaolin","year":"2019","journal-title":"Cell Prolif"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjz020","article-title":"Mitochondrial ros promote macrophage pyroptosis by inducing gsdmd oxidation","volume":"11","author":"Wang","year":"2019","journal-title":"J Mol Cell Biol"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.763516","article-title":"Proprotein convertase Subtilisin\/Kexin type 9 and inflammation: An updated review","volume":"9","author":"Wu","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2017.47","article-title":"Accelerated atherosclerosis development in C57bl6 mice by overexpressing aav-mediated Pcsk9 and partial carotid ligation","volume":"97","author":"Kumar","year":"2017","journal-title":"Lab Invest"},{"key":"B98","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s13075-020-02386-7","article-title":"Low levels of Pcsk9 are associated with remission in patients with rheumatoid arthritis treated with anti-Tnf-A: Potential underlying mechanisms","volume":"23","author":"Frosteg\u00e5rd","year":"2021","journal-title":"Arthritis Res Ther"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.037184","article-title":"Lipoprotein(a), Pcsk9 inhibition, and cardiovascular risk","volume":"139","author":"O\u2019Donoghue","year":"2019","journal-title":"Circulation"},{"key":"B100","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/nrd.2017.83","article-title":"Nine paths to Pcsk9 inhibition","volume":"16","author":"Mullard","year":"2017","journal-title":"Nat Rev Drug Discovery"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.11.011","article-title":"Effect of evolocumab on complex coronary disease requiring revascularization","volume":"77","author":"Oyama","year":"2021","journal-title":"J Am Coll Cardiol"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.046524","article-title":"Peripheral artery disease and venous thromboembolic events after acute coronary syndrome: Role of lipoprotein(a) and modification by alirocumab: Prespecified analysis of the odyssey outcomes randomized clinical trial","volume":"141","author":"Schwartz","year":"2020","journal-title":"Circulation"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz430","article-title":"Efficacy and safety of alirocumab and evolocumab: A systematic review and meta-analysis of randomized controlled trials","volume":"43","author":"Guedeney","year":"2019","journal-title":"Eur Heart J"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.11.011","article-title":"Small molecules as inhibitors of Pcsk9: Current status and future challenges","volume":"162","author":"Xu","year":"2019","journal-title":"Eur J med Chem"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61914-5","article-title":"Effect of an rna interference drug on the synthesis of proprotein convertase Subtilisin\/Kexin type 9 (Pcsk9) and the concentration of serum ldl cholesterol in healthy volunteers: A randomised, single-blind, placebo-controlled, phase 1 trial","volume":"383","author":"Fitzgerald","year":"2014","journal-title":"Lancet"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000001053","article-title":"Inclisiran: A novel agent for lowering apolipoprotein b-containing lipoproteins","volume":"78","author":"Warden","year":"2021","journal-title":"J Cardiovasc Pharmacol"},{"key":"B107","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1056\/NEJMoa1609243","article-title":"A highly durable rnai therapeutic inhibitor of Pcsk9","volume":"376","author":"Fitzgerald","year":"2017","journal-title":"New Engl J Med"},{"key":"B108","doi-asserted-by":"publisher","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":"New Engl J Med"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1007\/s40256-021-00477-7","article-title":"A critical review of the efficacy and safety of inclisiran","volume":"21","author":"Hardy","year":"2021","journal-title":"Am J Cardiovasc Drugs"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.2174\/0929867329666220930114429","article-title":"The immunogenic potential of Pcsk9 peptide vaccine in mice","volume":"30","author":"Ataei","year":"2023","journal-title":"Curr Med Chem"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-020-07041-6","article-title":"Pcsk9q\u03b2-003 vaccine attenuates atherosclerosis in apolipoprotein e-deficient mice","volume":"35","author":"Wu","year":"2021","journal-title":"Cardiovasc Drugs Ther"},{"key":"B112","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1186\/s12916-019-1457-8","article-title":"Therapeutic effect of nanoliposomal Pcsk9 vaccine in a mouse model of atherosclerosis","volume":"17","author":"Momtazi-Borojeni","year":"2019","journal-title":"BMC Med"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3800","article-title":"Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases","volume":"11","author":"Dinarello","year":"2012","journal-title":"Nat Rev Drug Discovery"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.10.072","article-title":"Epithelial il-18 equilibrium controls barrier function in colitis","volume":"163","author":"Nowarski","year":"2015","journal-title":"Cell"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1038\/nature11290","article-title":"Novel role of pkr in inflammasome activation and Hmgb1 release","volume":"488","author":"Lu","year":"2012","journal-title":"Nature"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3806","article-title":"A small-molecule inhibitor of the Nlrp3 inflammasome for the treatment of inflammatory diseases","volume":"21","author":"Coll","year":"2015","journal-title":"Nat Med"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-031210-101405","article-title":"The inflammasome nlrs in immunity, inflammation, and associated diseases","volume":"29","author":"Davis","year":"2011","journal-title":"Annu Rev Immunol"},{"key":"B118","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s10753-019-01098-8","article-title":"Target of Mcc950 in inhibition of Nlrp3 inflammasome activation: A literature review","volume":"43","author":"Wu","year":"2020","journal-title":"Inflammation"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.309575","article-title":"Nlrp3 inflammasome inhibition by Mcc950 reduces atherosclerotic lesion development in apolipoprotein e-deficient mice-brief report","volume":"37","author":"van der Heijden","year":"2017","journal-title":"Arteriosclerosis Thrombosis Vasc Biol"},{"key":"B120","doi-asserted-by":"publisher","first-page":"19305","DOI":"10.1038\/s41598-021-98437-3","article-title":"The selective Nlrp3 inhibitor Mcc950 hinders atherosclerosis development by attenuating inflammation and pyroptosis in macrophages","volume":"11","author":"Zeng","year":"2021","journal-title":"Sci Rep"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1210","article-title":"Biochemical and structural aspects of the atp-binding domain in inflammasome-forming human nlrp proteins","volume":"65","author":"MacDonald","year":"2013","journal-title":"IUBMB Life"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-019-0277-7","article-title":"Mcc950 directly targets the Nlrp3 atp-hydrolysis motif for inflammasome inhibition","volume":"15","author":"Coll","year":"2019","journal-title":"Nat Chem Biol"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20171419","article-title":"Identification of a selective and direct Nlrp3 inhibitor to treat inflammatory disorders","volume":"214","author":"Jiang","year":"2017","journal-title":"J Exp Med"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.08.017","article-title":"Nlrp3 phosphorylation is an essential priming event for inflammasome activation","volume":"68","author":"Song","year":"2017","journal-title":"Mol Cell"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/9286458","article-title":"Melatonin ameliorates the progression of atherosclerosis Via mitophagy activation and Nlrp3 inflammasome inhibition","volume":"2018","author":"Ma","year":"2018","journal-title":"Oxid Med Cell Longevity"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12449","article-title":"Melatonin prevents endothelial cell pyroptosis Via regulation of long noncoding rna Meg3\/Mir-223\/Nlrp3 axis","volume":"64","author":"Zhang","year":"2018","journal-title":"J Pineal Res"},{"key":"B127","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s13024-020-00372-w","article-title":"Nlrp12 collaborates with Nlrp3 and Nlrc4 to promote pyroptosis inducing ganglion cell death of acute glaucoma","volume":"15","author":"Chen","year":"2020","journal-title":"Mol Neurodegenerat"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1177\/0022034518775036","article-title":"Nlrp6 induces pyroptosis by activation of caspase-1 in gingival fibroblasts","volume":"97","author":"Liu","year":"2018","journal-title":"J Dental Res"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1126823\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T08:53:27Z","timestamp":1677056007000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1126823\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,22]]},"references-count":128,"alternative-id":["10.3389\/fimmu.2023.1126823"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1126823","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,22]]},"article-number":"1126823"}}