Association of proprotein convertase subtilisin/kexin type 9 (PCSK9) with cardiovascular risk in primary prevention

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 35, Issue 10, 2015, Pages 2254-2259

  Zhu, Yiming M ^a   Anderson, Todd J ^a   Sikdar, Khokan ^a   Fung, Marinda ^a   McQueen, Matthew J ^b   Lonn, Eva M ^b,c   Verma, Subodh ^d  

^a UNIVERSITY OF CALGARY   (Canada)

^b MCMASTER UNIVERSITY   (Canada)

^c ST MICHAEL'S HOSPITAL   (Canada)

^d ST MICHAEL'S HOSPITAL   (Canada)

Author keywords

Atherosclerosis; Body mass index; Cardiovascular diseases; LDL cholesterol; PCSK9 protein, human

Indexed keywords

HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INSULIN; KEXIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9; SUBTILISIN; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; BIOLOGICAL MARKER; PCSK9 PROTEIN, HUMAN; SERINE PROTEINASE;

ADULT; ARTERIAL WALL THICKNESS; ARTICLE; ATHEROSCLEROSIS; BODY MASS; CARDIOVASCULAR RISK; COHORT ANALYSIS; ENDOTHELIUM; FIRE FIGHTER; FOLLOW UP; HUMAN; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; PRIMARY PREVENTION; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; VASCULAR DISEASE; VELOCITY; ANALYSIS OF VARIANCE; BLOOD; CARDIOVASCULAR DISEASES; COMPARATIVE STUDY; CORONARY ARTERY DISEASE; MORTALITY; MULTIVARIATE ANALYSIS; PROCEDURES; PROGNOSIS; PROPORTIONAL HAZARDS MODEL; RISK FACTOR; SEVERITY OF ILLNESS INDEX; STATISTICAL MODEL; SURVIVAL RATE;

ANALYSIS OF VARIANCE; BIOMARKERS; BODY MASS INDEX; CARDIOVASCULAR DISEASES; CAROTID INTIMA-MEDIA THICKNESS; CHOLESTEROL, LDL; COHORT STUDIES; CORONARY ARTERY DISEASE; HUMANS; LINEAR MODELS; MALE; MIDDLE AGED; MULTIVARIATE ANALYSIS; PRIMARY PREVENTION; PROGNOSIS; PROPORTIONAL HAZARDS MODELS; PROPROTEIN CONVERTASES; RISK FACTORS; SERINE ENDOPEPTIDASES; SEVERITY OF ILLNESS INDEX; SURVIVAL RATE;

EID: 84942251605     PISSN: 10795642     EISSN: 15244636     Source Type: Journal    
DOI: 10.1161/ATVBAHA.115.306172     Document Type: Article

References (32)

1. Benjannet S, Rhainds D, Essalmani R, et al. NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol. J Biol Chem. 2004;279:48865-48875. doi: 10. 1074/jbc. M409699200.
2. Abifadel M, Varret M, Rabès J, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34:154-56.
3. Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006;354:1264-1272. doi: 10. 1056/NEJMoa054013.
4. Park SW, Moon YA, Horton JD. Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/ kexin type 9a in mouse liver. J Biol Chem. 2004;279:50630-50638. doi: 10. 1074/jbc. M410077200.
5. Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK, Hobbs HH. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet. 2005;37:161-165. doi: 10. 1038/ng1509.
6. Lagace TA, Curtis DE, Garuti R, McNutt MC, Park SW, Prather HB, Anderson NN, Ho YK, Hammer RE, Horton JD. Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice. J Clin Invest. 2006;116:2995-3005. doi: 10. 1172/ JCI29383.
7. Witztum JL, Steinberg D. Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest. 1991;88:1785-1792. doi: 10. 1172/JCI115499.
8. Cox DA, Vita JA, Treasure CB, Fish RD, Alexander RW, Ganz P, Selwyn AP. Atherosclerosis impairs flow-mediated dilation of coronary arteries in humans. Circulation. 1989;80:458-465.
9. Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: A systematic review and meta-analysis. Circulation. 2007;115:459-467. doi: 10. 1161/CIRCULATIONAHA. 106. 628875.
10. Anderson TJ, Charbonneau F, Title LM, Buithieu J, Rose MS, Conradson H, Hildebrand K, Fung M, Verma S, Lonn EM. Microvascular function predicts cardiovascular events in primary prevention: long-term results from the Firefighters and Their Endothelium (FATE) study. Circulation. 2011;123:163-169. doi: 10. 1161/CIRCULATIONAHA. 110. 953653.
11. Lakoski SG, Lagace TA, Cohen JC, Horton JD, Hobbs HH. Genetic and metabolic determinants of plasma PCSK9 levels. J Clin Endocrinol Metab. 2009;94:2537-2543. doi: 10. 1210/jc. 2009-0141.
12. Baass A, Dubuc G, Tremblay M, Delvin EE, O'Loughlin J, Levy E, Davignon J, Lambert M. Plasma PCSK9 is associated with age, sex, and multiple metabolic markers in a population-based sample of children and adolescents. Clin Chem. 2009;55:1637-1645. doi: 10. 1373/ clinchem. 2009. 126987.
13. Costet P, Cariou B, Lambert G, Lalanne F, Lardeux B, Jarnoux AL, Grefhorst A, Staels B, Krempf M. Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory elementbinding protein 1c. J Biol Chem. 2006;281:6211-6218. doi: 10. 1074/jbc. M508582200.
14. Blom DJ, Hala T, Bolognese M, et al; DESCARTES Investigators. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med. 2014;370:1809-1819. doi: 10. 1056/NEJMoa1316222.
15. Stein EA, Mellis S, Yancopoulos GD, Stahl N, Logan D, Smith WB, Lisbon E, Gutierrez M, Webb C, Wu R. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N Engl J Med. 2012;366:1108-1118.
16. Denis M, Marcinkiewicz J, Zaid A, Gauthier D, Poirier S, Lazure C, Seidah NG, Prat A. Gene inactivation of proprotein convertase subtilisin/ kexin type 9 reduces atherosclerosis in mice. Circulation. 2012;125:894-901. doi: 10. 1161/CIRCULATIONAHA. 111. 057406.
17. Cui Q, Ju X, Yang T, Zhang M, Tang W, Chen Q, Hu Y, Haas JV, Troutt JS, Pickard RT, Darling R, Konrad RJ, Zhou H, Cao G. Serum PCSK9 is associated with multiple metabolic factors in a large Han Chinese population. Atherosclerosis. 2010;213:632-636. doi: 10. 1016/j. Atherosclerosis. 2010. 09. 027.
18. Dubuc G, Tremblay M, Paré G, Jacques H, Hamelin J, Benjannet S, Boulet L, Genest J, Bernier L, Seidah NG, Davignon J. A new method for measurement of total plasma PCSK9: clinical applications. J Lipid Res. 2010;51:140-149. doi: 10. 1194/jlr. M900273-JLR200.
19. Kwakernaak AJ, Lambert G, Muller Kobold AC, Dullaart RP. Adiposity blunts the positive relationship of thyrotropin with proprotein convertase subtilisin-kexin type 9 levels in euthyroid subjects. Thyroid. 2013;23:166-172. doi: 10. 1089/thy. 2012. 0434.
20. Li S, Xu R, Zhang Y, Guo Y, Zhu C, Liu G, Dong Q, Li J. Relation of resistin to proprotein convertase subtilisin-kexin type 9 levels in coronary artery disease patients with different nutritional status. J Endocrinol Invest. 2015:1-9.
21. Miao J, Haas JT, Manthena P, Wang Y, Zhao E, Vaitheesvaran B, Kurland IJ, Biddinger SB. Hepatic insulin receptor deficiency impairs the SREBP-2 response to feeding and statins. J Lipid Res. 2014;55:659-667. doi: 10. 1194/jlr. M043711.
22. Roubtsova A, Munkonda MN, Awan Z, Marcinkiewicz J, Chamberland A, Lazure C, Cianflone K, Seidah NG, Prat A. Circulating proprotein convertase subtilisin/kexin 9 (PCSK9) regulates VLDLR protein and triglyceride accumulation in visceral adipose tissue. Arterioscler Thromb Vasc Biol. 2011;31:785-791. doi: 10. 1161/ATVBAHA. 110. 220988.
23. Le May C, Kourimate S, Langhi C, Chétiveaux M, Jarry A, Comera C, Collet X, Kuipers F, Krempf M, Cariou B, Costet P. Proprotein convertase subtilisin kexin type 9 null mice are protected from postprandial triglyceridemia. Arterioscler Thromb Vasc Biol. 2009;29:684-690. doi: 10. 1161/ ATVBAHA. 108. 181586.
24. Lambert G, Ancellin N, Charlton F, Comas D, Pilot J, Keech A, Patel S, Sullivan DR, Cohn JS, Rye KA, Barter PJ. Plasma PCSK9 concentrations correlate with LDL and total cholesterol in diabetic patients and are decreased by fenofibrate treatment. Clin Chem. 2008;54:1038-1045. doi: 10. 1373/clinchem. 2007. 099747.
25. Mayne J, Raymond A, Chaplin A, Cousins M, Kaefer N, Gyamera-Acheampong C, Seidah NG, Mbikay M, Chrétien M, Ooi TC. Plasma PCSK9 levels correlate with cholesterol in men but not in women. Biochem Biophys Res Commun. 2007;361:451-456. doi: 10. 1016/j. bbrc. 2007. 07. 029.
26. Yeboah J, Folsom AR, Burke GL, Johnson C, Polak JF, Post W, Lima JA, Crouse JR, Herrington DM. Predictive value of brachial flow-mediated dilation for incident cardiovascular events in a population-based study: the multi-ethnic study of atherosclerosis. Circulation. 2009;120:502-509. doi: 10. 1161/CIRCULATIONAHA. 109. 864801.
27. Yan RT, Anderson TJ, Charbonneau F, Verma S, Lonn E. Relationship between carotid artery intima-media thickness and brachial artery flowmediated dilation in middle-aged healthy men. J Am Coll Cardiol. 2005;45:1980-1986.
28. Salonen R, Salonen JT. Determinants of carotid intima-media thickness: A population-based ultrasonography study in eastern Finnish men. J Intern Med. 1991;229:225-231.
29. Huang CC, Fornage M, Lloyd-Jones DM, Wei GS, Boerwinkle E, Liu K. Longitudinal association of PCSK9 sequence variations with low-density lipoprotein cholesterol levels: the Coronary Artery Risk Development in Young Adults Study. Circ Cardiovasc Genet. 2009;2:354-361. doi: 10. 1161/CIRCGENETICS. 108. 828467.
30. Norata GD, Garlaschelli K, Grigore L, Raselli S, Tramontana S, Meneghetti F, Artali R, Noto D, Cefalù AB, Buccianti G. Effects of PCSK9 variants on common carotid artery intima media thickness and relation to ApoE alleles. Atherosclerosis. 2010;208:177-182. doi: 10. 1016/j. Atherosclerosis. 2009. 06. 023.
31. Simon A, Megnien JL, Chironi G. The value of carotid intima-media thickness for predicting cardiovascular risk. Arterioscler Thromb Vasc Biol. 2010;30:182-185. doi: 10. 1161/ATVBAHA. 109. 196980.
32. Gauthier M, Pérusse JR, Awan Z, Bouchard A, Tessier S, Champagne J, Krastins B, Byram G, Chabot K, Garneau P. A semi-automated mass spectrometric immunoassay coupled to selected reaction monitoring (MSIA-SRM) reveals novel relationships between circulating PCSK9 and metabolic phenotypes in patient cohorts. Methods. 2015; 81: 66-73.