{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:53:58Z","timestamp":1792500838864,"version":"4.5.0"},"reference-count":86,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T00:00:00Z","timestamp":1550016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The pathogenesis of hypertension, as a multifactorial trait, is complex. High blood pressure levels, in turn, concur with the development of cardiovascular damage. Abnormalities of several neurohormonal mechanisms controlling blood pressure homeostasis and cardiovascular remodeling can contribute to these pathological conditions. The natriuretic peptide (NP) family (including ANP (atrial natriuretic peptide), BNP (brain natriuretic peptide), and CNP (C-type natriuretic peptide)), the NP receptors (NPRA, NPRB, and NPRC), and the related protease convertases (furin, corin, and PCSK6) constitute the NP system and represent relevant protective mechanisms toward the development of hypertension and associated conditions, such as atherosclerosis, stroke, myocardial infarction, heart failure, and renal injury. Initially, several experimental studies performed in different animal models demonstrated a key role of the NP system in the development of hypertension. Importantly, these studies provided relevant insights for a better comprehension of the pathogenesis of hypertension and related cardiovascular phenotypes in humans. Thus, investigation of the role of NPs in hypertension offers an excellent example in translational medicine. In this review article, we will summarize the most compelling evidence regarding the molecular mechanisms underlying the physiological and pathological impact of NPs on blood pressure regulation and on hypertension development. We will also discuss the protective effect of NPs toward the increased susceptibility to hypertensive target organ damage.<\/jats:p>","DOI":"10.3390\/ijms20040798","type":"journal-article","created":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T03:21:46Z","timestamp":1550114506000},"page":"798","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Molecular Implications of Natriuretic Peptides in the Protection from Hypertension and Target Organ Damage Development"],"prefix":"10.3390","volume":"20","author":[{"given":"Speranza","family":"Rubattu","sequence":"first","affiliation":[{"name":"Department of Clinical and Molecular Medicine, School of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy"},{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Forte","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Marchitti","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Volpe","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, School of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy"},{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.33549\/physiolres.931913","article-title":"The interaction of genetic and environmental factors in the etiology of hypertension","volume":"58","author":"Kunes","year":"2009","journal-title":"Physiol. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1056\/NEJM199807303390507","article-title":"Natriuretic peptides","volume":"339","author":"Levin","year":"1998","journal-title":"NEJM"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1093\/eurheartj\/eht466","article-title":"Natriuretic peptides in cardiovascular diseases: Current use and perspectives","volume":"35","author":"Volpe","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_4","first-page":"583","article-title":"Acute hemodynamic effects of atrial natriuretic peptide in essential hypertension","volume":"25","author":"Volpe","year":"1998","journal-title":"Kidney Int. Suppl."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1253\/jcj.50.1181","article-title":"A comparative study on the hemodynamic, renal and endocrine effects of alpha-human atrial natriuretic polypeptide in normotensive persons and patients with essential hypertension","volume":"50","author":"Ishii","year":"1986","journal-title":"Jpn. Circ. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1210\/jcem-63-4-815","article-title":"Plasma levels of atrial natriuretic peptide in primary aldosteronism and essential hypertension","volume":"63","author":"Yamaji","year":"1986","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3109\/08037059209077511","article-title":"Plasma atrial natriuretic peptide (ANP) concentration in patients with pheochromocytoma","volume":"1","author":"Stepniakowski","year":"1992","journal-title":"Blood Press"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1080\/15216540212336","article-title":"Atrial natriuretic peptide prohormone gene expression: Hormones and diseases that upregulate its expression","volume":"53","author":"Vesely","year":"2002","journal-title":"IUBMB Life"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.jjcc.2011.12.007","article-title":"COLD-CHF Investigators. Comparative study of therapeutic effects of short- and long-acting loop diuretics in outpatients with chronic heart failure (COLD-CHF)","volume":"59","author":"Miyata","year":"2012","journal-title":"J. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1126\/science.7839143","article-title":"Genetic decreases in atrial natriuretic peptide and salt-sensitive hypertension","volume":"267","author":"John","year":"1995","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1161\/01.HYP.16.3.301","article-title":"Hypotension in transgenic mice expressing atrial natriuretic factor fusion genes","volume":"16","author":"Steinhelper","year":"1990","journal-title":"Hypertension"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"14730","DOI":"10.1073\/pnas.94.26.14730","article-title":"Hypertension, cardiac hypertrophy, and sudden death in mice lacking natriuretic peptide receptor A","volume":"94","author":"Oliver","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-407680-8.00001-4","article-title":"BNP molecular forms and processing by the cardiac serine protease corin","volume":"61","author":"Ichiki","year":"2013","journal-title":"Adv. Clin. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4239","DOI":"10.1073\/pnas.070371497","article-title":"Cardiac fibrosis in mice lacking brain natriuretic peptide","volume":"97","author":"Tamura","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1161\/HYPERTENSIONAHA.115.05610","article-title":"B-type natriuretic peptide deletion leads to progressive hypertension, associated organ damage, and reduced survival: Novel model for human hypertension","volume":"66","author":"Holditch","year":"2015","journal-title":"Hypertension"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/sj.jhh.1002228","article-title":"Atrial natriuretic peptide (ANP) gene promoter variant and increased susceptibility to early development of hypertension in humans","volume":"21","author":"Rubattu","year":"2007","journal-title":"J. Hum. Hypertens."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1042\/cs0980251","article-title":"Genetic analysis of the atrial natriuretic peptide gene in essential hypertension","volume":"98","author":"Kato","year":"2000","journal-title":"Clin. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1161\/HYPERTENSIONAHA.107.097634","article-title":"Natriuretic peptide precursor A gene polymorphisms and risk of blood pressure progression and incident hypertension","volume":"50","author":"Conen","year":"2007","journal-title":"Hypertension"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1016\/j.clinthera.2005.11.008","article-title":"Association between human atrial natriuretic peptide Val7Met polymorphism and baseline blood pressure, plasma trough irbesartan concentrations, and the antihypertensive efficacy of irbesartan in rural Chinese patients with essential hypertension","volume":"27","author":"Zhang","year":"2005","journal-title":"Clin. Ther."},{"key":"ref_20","first-page":"1316","article-title":"HpaII-polymorphism of the atrial natriuretic peptide gene and essential hypertension in whites","volume":"10","author":"Beige","year":"1997","journal-title":"Am. J. Hypertens."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/ng.361","article-title":"Genome-wide association study identifies eight loci associated with blood pressure","volume":"41","author":"Johnson","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1161\/CIRCGENETICS.114.000624","article-title":"Circulating atrial natriuretic peptide genetic association study identifies a novel gene cluster associated with stroke in whites","volume":"8","author":"Pereira","year":"2015","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3378","DOI":"10.1172\/JCI67383","article-title":"Atrial natriuretic peptide is negatively regulated by microRNA-425","volume":"123","author":"Arora","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.jacc.2011.05.011","article-title":"A genetic variant of the atrial natriuretic peptide gene is associated with cardiometabolic protection in the general community","volume":"58","author":"Cannone","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2850","DOI":"10.2337\/dc12-2337","article-title":"The atrial natriuretic peptide genetic variant rs5068 is associated with a favorable cardiometabolic phenotype in a Mediterranean population","volume":"36","author":"Cannone","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/CS20130427","article-title":"Atrial natriuretic peptide gene variants and circulating levels: Implications in cardiovascular diseases","volume":"127","author":"Rubattu","year":"2014","journal-title":"Clin. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1161\/CIRCGENETICS.114.000900","article-title":"Genome-wide association analysis of B-type natriuretic peptide in blacks: The Jacson Heart Study","volume":"8","author":"Musani","year":"2015","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1093\/hmg\/ddw012","article-title":"Genome-wide association and Mendelian randomization study of NT-proBNP in patients with acute coronary syndrome","volume":"25","author":"Johansson","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1093\/hmg\/ddr035","article-title":"Genome-wide association analysis and fine mapping of NT-proBNP level provide novel insight into the role of the MTHFR-CLCN6-NPPA-NPPB gene cluster","volume":"20","author":"Pattaro","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Folkersen, L., Fauman, E., Sabater-Lleal, M., Strawbridge, R.J., Franberg, M., Sennblad, B., Baldassarre, D., Veglia, F., Humphries, S.E., and Rauramaa, R. (2017). Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1006706"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e001713","DOI":"10.1161\/CIRCGENETICS.117.001713","article-title":"Genome-Wide Association Study implicates atrial natriuretic peptide rather than B-type natriuretic peptide in the regulation of blood pressure in the general population","volume":"10","author":"Salo","year":"2017","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s10557-007-6007-5","article-title":"Genetic variation in the B-type natriuretic peptide pathway affects BNP levels","volume":"21","author":"Lanfear","year":"2007","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e005257","DOI":"10.1161\/JAHA.116.005257","article-title":"An NPPB promoter polymorphism associated with elevated N-terminal pro-B-type natriuretic peptide and lower blood pressure, hypertension, and mortality","volume":"6","author":"Seidelmann","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8525","DOI":"10.1073\/pnas.150149097","article-title":"Corin, a transmembrane cardiac serine protease, acts as a pro-atrial natriuretic peptide-converting enzyme","volume":"97","author":"Yan","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"16900","DOI":"10.1074\/jbc.M201503200","article-title":"Processing of pro-atrial natriuretic peptide by corin in cardiac myocytes","volume":"277","author":"Wu","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1073\/pnas.0407234102","article-title":"Hypertension in mice lacking the proatrial natriuretic peptide convertase corin","volume":"102","author":"Chan","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1038\/nm.3920","article-title":"PCSK6-mediated corin activation is essential for normal blood pressure","volume":"21","author":"Chen","year":"2015","journal-title":"Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1161\/CIRCRESAHA.115.307875","article-title":"Novel insights into the mechanisms regulating pro-atrial natriuretic peptide cleavage in the heart and blood pressure regulation. Proprotein Convertase Subtilisin\/Kexin 6 is the corin activating enzyme","volume":"118","author":"Volpe","year":"2016","journal-title":"Circ. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1161\/01.HYP.0000258566.95867.9e","article-title":"Corin I555 (P568) is associated with enhanced cardiac hypertrophy response to increased systemic afterload","volume":"49","author":"Rame","year":"2007","journal-title":"Hypertension"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1161\/CIRCHEARTFAILURE.109.866822","article-title":"Dysfunctional corin I555(P568) allele is associated with impaired brain natriuretic peptide processing and advserse outcomes in blacks with systolic heart failure: Results from the genetic risk assessment in heart failure substudy","volume":"2","author":"Rame","year":"2009","journal-title":"Circ. Heart Fail."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"17909","DOI":"10.1074\/jbc.M114.551424","article-title":"Corin mutations K317E and S472G from preeclamptic patients alter zymogen activation and cell surface targeting","volume":"289","author":"Dong","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1002\/humu.23318","article-title":"Identification and functional analysis of CORIN variants in hypertensive patients","volume":"38","author":"Zhang","year":"2017","journal-title":"Hum. Mutat."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Li, N., Luo, W., Juhong, Z., Yang, J., Wang, H., Zhou, L., and Chang, J. (2010). Associations between genetic variations in the FURIN gene and hypertension. BMC Med. Genet., 11.","DOI":"10.1186\/1471-2350-11-124"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"International Consortium for Blood Pressure Genome-Wide Association, Eehret, G.B., Munroe, P.B., Rice, K.M., Bochud, M., Johnson, A.D., Chasman, D.I., Smith, A.V., Tobin, M.D., and Verwoert, G.C. (2011). Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature, 478, 103\u2013109.","DOI":"10.1038\/nature10405"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1534\/g3.115.016915","article-title":"Novel genes affecting blood pressure detected via gene-based association analysis","volume":"5","author":"Zhang","year":"2015","journal-title":"G3"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1161\/01.RES.86.8.841","article-title":"Functional deletion mutation of the 5\u2019-flanking region of type A human natriuretic peptide receptor gene and its association with essential hypertension and left ventricular hypertrophy in the Japanese","volume":"86","author":"Nakayama","year":"2000","journal-title":"Circ. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"8786","DOI":"10.4238\/2015.August.3.2","article-title":"Correlation between natriuretic peptide receptor C (NPR3) gene polymorphisms and hypertension in the Dai people of China","volume":"14","author":"Sun","year":"2015","journal-title":"Genet. Mol. Res. GMR"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1097\/00004872-200308000-00012","article-title":"Allelic variants of natriuretic peptide receptor genes are associated with family history of hypertension and cardiovascular phenotype","volume":"21","author":"Pitzalis","year":"2003","journal-title":"J. Hypertens."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1093\/hmg\/ddx375","article-title":"The biological impact of blood pressure-associated genetic variants in the natriuretic peptide receptor C gene on human vascular smooth muscle","volume":"27","author":"Ren","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s40292-015-0115-2","article-title":"Hypertension and stroke: Epidemiological aspects and clinical evaluation","volume":"23","author":"Pistola","year":"2016","journal-title":"High Blood Press. Cardiovasc. Prev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/ng0896-429","article-title":"Chromosomal mapping of genetic loci contributing to stroke in an animal model of a complex human disease","volume":"13","author":"Rubattu","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1161\/01.RES.85.10.900","article-title":"Altered structure, regulation and function of the gene encoding atrial natriuretic peptide in the stroke-prone spontaneously hypertensive rat","volume":"85","author":"Rubattu","year":"1999","journal-title":"Circ. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/S0196-9781(01)00626-X","article-title":"Effect of a regulatory mutation on the rat atrial natriuretic peptide gene transcription","volume":"23","author":"Rubattu","year":"2002","journal-title":"Peptides"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1097\/00004872-199917121-00011","article-title":"A differential brain ANP expression cosegregates with occurrence of early stroke in the stroke-prone phenotype of the spontaneously hypertensive rat","volume":"17","author":"Rubattu","year":"1999","journal-title":"J. Hypertens."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/ng0897-364","article-title":"Sensitivity to cerebral ischaemic insult in a rat model of stroke is determined by a single genetic locus","volume":"16","author":"Jeffs","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1161\/01.HYP.33.1.290","article-title":"Genes encoding atrial and brain natriuretic peptides as candidates for sensitivity to brain ischemia in stroke-prone hypertensive rats","volume":"33","author":"Brosnan","year":"1999","journal-title":"Hypertension"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2018.05.014","article-title":"Molecular mechanisms underlying the neuroprotective role of atrial natriuretic peptide in experimental acute ischemic stroke","volume":"472","author":"Burguete","year":"2018","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1097\/HJH.0000000000001762","article-title":"Effects of dual Angiotensin type 1 receptor\/neprilysin inhibition versus Angiotensin type 1 receptor inhibition on target organ injury in the stroke-prone spontaneously hypertensive rat","volume":"36","author":"Rubattu","year":"2018","journal-title":"J. Hypertens."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1161\/01.STR.0000119381.52589.AB","article-title":"Atrial natriuretic peptide gene polymorphisms and the risk of ischemic stroke in humans","volume":"35","author":"Rubattu","year":"2004","journal-title":"Stroke"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1161\/HYPERTENSIONAHA.113.01344","article-title":"Atrial natriuretic peptide genetic variant rs5065 and riskfor cardiovascular disease in the general community: A 9-year follow-up study","volume":"62","author":"Cannone","year":"2013","journal-title":"Hypertension"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1097\/HJH.0b013e32832d229f","article-title":"ROS-mediated differential effects of the human atrial natriuretic peptide T2238C genetic variant on endothelial cells in vitro","volume":"27","author":"Scarpino","year":"2009","journal-title":"J. Hypertens."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1161\/CIRCRESAHA.113.301325","article-title":"The C2238 Atrial Natriuretic Peptide Molecular Variant is Associated with Endothelial Damage and Dysfunction Through Natriuretic Peptide Receptor C Signaling","volume":"112","author":"Sciarretta","year":"2013","journal-title":"Circ. Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Rubattu, S., Marchitti, S., Bianchi, F., Di Castro, S., Stanzione, R., Cotugno, M., Bozzao, C., Sciarretta, S., and Volpe, M. (2014). The C2238\/\u03b1ANP variant is a negative modulator of both viability and function of coronary artery smooth muscle cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113108"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e2033","DOI":"10.1038\/cddis.2015.370","article-title":"C2238\/\u03b1ANP modulates Apolipoprotein E through Egr-1\/miR199a in vascular smooth muscle cells in vitro","volume":"6","author":"Stanzione","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3797","DOI":"10.1038\/s41598-017-03679-9","article-title":"C2238 ANP gene variant promotes increased platelet aggregation through the activation of Nox2 and the reduction of cAMP","volume":"7","author":"Carnevale","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1007\/s12265-017-9774-9","article-title":"T2238C atrial natriuretic peptide gene variant and the response to antiplatelet therapy in stable ischemic heart disease patients","volume":"11","author":"Strisciuglio","year":"2018","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Rubattu, S., Sciarretta, S., Marchitti, S., Bianchi, F., Forte, M., and Volpe, M. (2018). The T2238C atrial natriuretic peptide molecular variant and the risk of cardiovascular diseases. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020540"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1001\/jama.299.3.296","article-title":"Pharmacogenetic association of the NPPA T2238C genetic variant with cardiovascular disease outcomes in patients with hypertension","volume":"299","author":"Lynch","year":"2008","journal-title":"JAMA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s00109-011-0801-z","article-title":"Molecular mechanisms underlying cardiac antihypertrophic and antifibrotic effects of natriuretic peptides","volume":"90","author":"Calvieri","year":"2012","journal-title":"J. Mol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1172\/JCI18389","article-title":"A friend within the heart: Natriuretic peptide receptor signaling","volume":"111","author":"Molkentin","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.jacc.2005.12.081","article-title":"Association of atrial natriuretic and type-A natriuretic peptide receptor gene polymorphisms with left ventricular mass in human essential hypertension","volume":"48","author":"Rubattu","year":"2006","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1097\/HJH.0b013e32803cae3c","article-title":"Reduced levels of pro-atrial natriuretic peptide in hypertensive patients with metabolic syndrome and their relationship with LVH","volume":"25","author":"Rubattu","year":"2007","journal-title":"J. Hypertens."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1042\/CS20160398","article-title":"Localization of corin and atrial natriuretic peptide expression in human renal segments","volume":"130","author":"Dong","year":"2016","journal-title":"Clin. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s10157-014-0982-1","article-title":"Aggravated renal tubular damage and interstitial fibrosis in mice lacking guanylyl cyclase A (GC-A), a receptor for atrial and B-type natriuretic peptides","volume":"19","author":"Yoshihara","year":"2015","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Romero, M., Caniffi, C., Bouchet, G., Costa, M.A., Elesgaray, R., Arranza, C., and Tomat, A.L. (2015). Chronic treatment with atrial natriuretic peptide in spontaneously hypertensive rats: Beneficial renal effects and sex differences. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120362"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.ejheart.2004.01.001","article-title":"N-terminal pro brain natriuretic peptide in arterial hypertension\u2014A marker for left ventricular dimensions and prognosis","volume":"6","author":"Hildebrandt","year":"2004","journal-title":"Eur. J. Heart Fail."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1097\/01.hjh.0000239288.10013.04","article-title":"N-terminal brain natriuretic peptide predicted cardiovascular events stronger than high-sensitivity C-reactive protein in hypertension: A LIFE substudy","volume":"24","author":"Olsen","year":"2006","journal-title":"J. Hypertens."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1056\/NEJMoa0900094","article-title":"Genomewide association studies of stroke","volume":"360","author":"Ikram","year":"2009","journal-title":"NEJM"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.ejim.2012.09.002","article-title":"Association of a single nucleotide polymorphism of the NPR3 gene promoter with early onset ischemic stroke in an Italian cohort","volume":"24","author":"Rubattu","year":"2013","journal-title":"Eur. J. Intern. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s40292-015-0112-5","article-title":"Angiotensin II receptor blocker nephrilysin inhibitor (ARNI): New avenues in cardiovascular therapy","volume":"22","author":"Volpe","year":"2015","journal-title":"High Blood Press. Cardiovasc. Prev."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.pharmthera.2014.05.002","article-title":"Current role of neprilysin inhibitors in hypertension and heart failure","volume":"144","author":"Atar","year":"2014","journal-title":"Pharmacol. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1161\/HYPERTENSIONAHA.113.02002","article-title":"Efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Asian patients with hypertension: A randomized, double-blind, placebo-controlled study","volume":"63","author":"Kario","year":"2014","journal-title":"Hypertension"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/S0140-6736(09)61966-8","article-title":"Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: A randomized, double-blind, placebo-controlled, active comparator study","volume":"375","author":"Ruilope","year":"2010","journal-title":"Lancet"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1161\/HYPERTENSIONAHA.116.08484","article-title":"Effects of Sacubitril\/Valsartan (LCZ696) on natriuresis, diuresis, blood pressures, and NT-proBNP in salt-sensitive hypertension","volume":"69","author":"Wang","year":"2017","journal-title":"Hypertension"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1093\/ajh\/hpv015","article-title":"LCZ696, Angiotensin II receptor-neprilysin inhibitor, ameliorates high-salt-induced hypertension and cardiovascular injury more than valsartan alone","volume":"28","author":"Kusaka","year":"2015","journal-title":"Am. J. Hypertens."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1161\/HYPERTENSIONAHA.116.08556","article-title":"Effects of sacubitril\/valsartan versus olmesartan on central hemodynamics in the erderly with systolic hypertension: The PARAMETER study","volume":"69","author":"Williams","year":"2017","journal-title":"Hypertension"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/4\/798\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:31:37Z","timestamp":1760185897000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/4\/798"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,13]]},"references-count":86,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,2]]}},"alternative-id":["ijms20040798"],"URL":"https:\/\/doi.org\/10.3390\/ijms20040798","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,13]]}}}