Guo Y, Yan B, Gui Y, Tang Z, Tai S et al (2021) Physiology and role of PCSK9 in vascular disease: potential impact of localized PCSK9 in vascular wall. J Cell Physiol 236(4):2333–2351. https://doi.org/10.1002/jcp.30025
Article CAS PubMed Google Scholar
Seidah NG, Prat A (2022) The multifaceted biology of PCSK9. Endocr Rev 43(3):558–582. https://doi.org/10.1210/endrev/bnab035
Yurtseven E, Ural D, Baysal K, Tokgözoğlu L (2020) An update on the role of PCSK9 in atherosclerosis. J Atheroscler Thromb 27(9):909–918. https://doi.org/10.5551/jat.55400
Article CAS PubMed PubMed Central Google Scholar
Matías-Pérez D, Pérez-Santiago AD, Sánchez Medina MA, Alpuche Osorno JJ, García-Montalvo IA (2021) PCSK9 gene participates in the development of primary dyslipidemias. Balkan J Med Genet 24(1):5–14. https://doi.org/10.2478/bjmg-2021-0009
Article CAS PubMed PubMed Central Google Scholar
Hopkins PN, Defesche J, Fouchier SW, Bruckert E, Luc G et al (2015) Characterization of autosomal dominant hypercholesterolemia caused by PCSK9 gain of function mutations and its specific treatment with alirocumab, a PCSK9 Monoclonal Antibody. Circ Cardiovasc Genet 8(6):823–831. https://doi.org/10.1161/CIRCGENETICS.115.001129
Article CAS PubMed PubMed Central Google Scholar
Miyake Y, Kimura R, Kokubo Y, Okayama A, Tomoike H et al (2008) 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. Atherosclerosis 196(1):29–36. https://doi.org/10.1016/j.atherosclerosis.2006.12.035
Article CAS PubMed Google Scholar
Zhao Z, Tuakli-Wosornu Y, Lagace TA, Kinch L, Grishin NV et al (2006) Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote. Am J Hum Genet 79(3):514–523. https://doi.org/10.1086/507488
Article CAS PubMed PubMed Central Google Scholar
Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH (2006) Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 354(12):1264–1272. https://doi.org/10.1056/NEJMoa054013
Article CAS PubMed Google Scholar
Hooper AJ, Marais AD, Tanyanyiwa DM, Burnett JR (2007) The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population. Atherosclerosis 193(2):445–448. https://doi.org/10.1016/j.atherosclerosis.2006.08.039
Article CAS PubMed Google Scholar
Cariou B, Ouguerram K, Zaïr Y, Guerois R, Langhi C et al (2009) PCSK9 dominant negative mutant results in increased LDL catabolic rate and familial hypobetalipoproteinemia. Arterioscler Thromb Vasc Biol 29(12):2191–2197. https://doi.org/10.1161/ATVBAHA.109.194191
Article CAS PubMed Google Scholar
Da Dalt L, Ruscica M, Bonacina F, Balzarotti G, Dhyani A et al (2019) PCSK9 deficiency reduces insulin secretion and promotes glucose intolerance: the role of the low-density lipoprotein receptor. Eur Heart J 40(4):357–368. https://doi.org/10.1093/eurheartj/ehy357
Article CAS PubMed Google Scholar
Schmidt AF, Swerdlow DI, Holmes MV, Patel RS, Fairhurst-Hunter Z et al (2017) PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study. Lancet Diabetes Endocrinol 5(2):97–105. https://doi.org/10.1016/S2213-8587(16)30396-5
Article CAS PubMed PubMed Central Google Scholar
Lotta LA, Sharp SJ, Burgess S, Perry JRB, Stewart ID et al (2016) Association between low-density lipoprotein cholesterol-lowering genetic variants and risk of type 2 diabetes: a meta-analysis. JAMA 316(13):1383–1391. https://doi.org/10.1001/jama.2016.14568
Article CAS PubMed PubMed Central Google Scholar
Ference BA, Robinson JG, Brook RD, Catapano AL, Chapman MJ et al (2016) Variation in PCSK9 and HMGCR and risk of cardiovascular disease and diabetes. N Engl J Med 375(22):2144–2153. https://doi.org/10.1056/NEJMoa1604304
Article CAS PubMed Google Scholar
Da Dalt L, Castiglioni L, Baragetti A, Audano M, Svecla M et al (2021) PCSK9 deficiency rewires heart metabolism and drives heart failure with preserved ejection fraction. Eur Heart J 42(32):3078–3090. https://doi.org/10.1093/eurheartj/ehab431
Article CAS PubMed PubMed Central Google Scholar
Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD et al (2017) Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 376(18):1713–1722. https://doi.org/10.1056/NEJMoa1615664
Article CAS PubMed Google Scholar
Sabatine MS, Leiter LA, Wiviott SD, Giugliano RP, Deedwania P et al (2017) 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. Lancet Diabetes Endocrinol 5(12):941–950. https://doi.org/10.1016/S2213-8587(17)30313-3
Article CAS PubMed Google Scholar
Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA et al (2018) Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med 379(22):2097–2107. https://doi.org/10.1056/NEJMoa1801174
Article CAS PubMed Google Scholar
Pirillo A, Catapano AL (2022) Inclisiran: how widely and when should we use it? Curr Atheroscler Rep 24(10):803–811. https://doi.org/10.1007/s11883-022-01056-0
Article CAS PubMed PubMed Central Google Scholar
Ray KK, Stoekenbroek RM, Kallend D, Nishikido T, Leiter LA et al (2019) Effect of 1 or 2 doses of inclisiran on low-density lipoprotein cholesterol levels: one-year follow-up of the ORION-1 randomized clinical trial. JAMA Cardiol 4(11):1067–1075. https://doi.org/10.1001/jamacardio.2019.3502
Article PubMed PubMed Central Google Scholar
Punch E, Klein J, Diaba-Nuhoho P, Morawietz H, Garelnabi M (2022) Effects of PCSK9 targeting: alleviating oxidation, inflammation, and atherosclerosis. J Am Heart Assoc 11(3):e023328. https://doi.org/10.1161/JAHA.121.023328
Article CAS PubMed PubMed Central Google Scholar
Seidah NG, Awan Z, Chretien M, Mbikay M (2014) PCSK9: a key modulator of cardiovascular health. Circ Res 114(6):1022–1036. https://doi.org/10.1161/CIRCRESAHA.114.301621
Article CAS PubMed Google Scholar
Seidah NG, Benjannet S, Wickham L, Marcinkiewicz J, Jasmin SB et al (2003) The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc Natl Acad Sci U S A 100(3):928–933. https://doi.org/10.1073/pnas.0335507100
Article CAS PubMed PubMed Central Google Scholar
Saavedra YG, Zhang J, Seidah NG (2013) PCSK9 prosegment chimera as novel inhibitors of LDLR degradation. PLoS ONE 8(8):e72113. https://doi.org/10.1371/journal.pone.0072113
Article CAS PubMed Google Scholar
Holla ØL, Laerdahl JK, Strøm TB, Tveten K, Cameron J et al (2011) Removal of acidic residues of the prodomain of PCSK9 increases its activity towards the LDL receptor. Biochem Biophys Res Commun 406(2):234–238. https://doi.org/10.1016/j.bbrc.2011.02.023
Article CAS PubMed Google Scholar
Benjannet S, Saavedra YG, Hamelin J, Asselin MC, Essalmani R et al (2010) Effects of the prosegment and pH on the activity of PCSK9: evidence for additional processing events. J Biol Chem 285(52):40965–40978. https://doi.org/10.1074/jbc.M110.154815
Comments (0)