PCSK9 inhibition-A new thrust in the prevention of heart disease: Genetics does it again

Canadian Journal of Cardiology

Volumn 29, Issue 8, 2013, Pages 899-901

  Roberts, Robert ^a  

^a UNIVERSITY OF OTTAWA HEART INSTITUTE   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

3 HYDROXY 3 METHYLGLUTARYL COENZYME A; ACETIC ACID DERIVATIVE; AMINO ACID; APOLIPOPROTEIN E; ATORVASTATIN; CHOLESTEROL; GLYCOPROTEIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INSULIN; LEPTIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN RECEPTOR; MONOCLONAL ANTIBODY; PROTEIN PCSK 9; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; VERY LOW DENSITY LIPOPROTEIN;

ATHEROSCLEROSIS; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL SYNTHESIS; COENZYME; CORONARY ARTERY ATHEROSCLEROSIS; CORONARY ARTERY DISEASE; EDITORIAL; ENDOCYTOSIS; FAMILIAL HYPERCHOLESTEROLEMIA; GAIN OF FUNCTION MUTATION; GENE MUTATION; GENETIC ANALYSIS; GENETIC PREDISPOSITION; GENOTYPE; HEART DISEASE; HEART INFARCTION; HUMAN; HYPERCHOLESTEROLEMIA; INSULIN RESISTANCE; LIVER CELL; LOSS OF FUNCTION MUTATION; PROTEIN BINDING; PROTEIN DEGRADATION; RISK FACTOR; SECONDARY PREVENTION;

APOLIPOPROTEINS E; FEMALE; HUMANS; INSULIN; INSULIN RESISTANCE; LEPTIN; LIPIDS; MALE; PROPROTEIN CONVERTASES; SERINE ENDOPEPTIDASES;

EID: 84881029396     PISSN: 0828282X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cjca.2013.04.014     Document Type: Editorial

References (18)

1. Brown M.S., Goldstein J.L. Familial hypercholesterolemia: a genetic defect in the low-density lipoprotein receptor. NEngl J Med 1976, 294:1386-1390.
2. Seidah N.G., Benjannet S., Wickham L., et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc Natl Acad Sci U S A 2003, 100:928-933.
3. Abifadel M., Varret M., Rabes J.P., et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 2003, 34:154-156.
4. Cohen J., Pertsemlidis A., Kotowski I.K., et al. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet 2005, 37:161-165.
5. Maxwell K.N., Breslow J.L. Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype. Proc Natl Acad Sci U S A 2004, 101:7100-7105.
6. Davignon J., Dubuc G., Seidah N.G. The influence of PCSK9 polymorphisms on serum low-density lipoprotein cholesterol and risk of atherosclerosis. Curr Atheroscler Rep 2010, 12:308-315.
7. Heller D.A., de Faire U., Pedersen N.L., Dahlen G., McClearn G.E. Genetic and environmental influences on serum lipid levels in twins. NEngl J Med 1993, 328:1150-1156.
8. Rao D.C., Laskarzewski P.M., Morrison J.A., et al. The Cincinnati Lipid Research Clinic family study: cultural and biological determinants of lipids and lipoprotein concentrations. Am J Hum Genet 1982, 34:888-903.
9. Awan Z., Delvin E.E., Levy E., et al. Regional distribution and metabolic effect of PCSK9 insLEU and R46L gene mutations and apoE genotype. Can J Cardiol 2013, 29:927-933.
10. Hovingh G.K., Davidson M.H., Kastelein J.J., O'Connor A.M. Diagnosis and treatment of familial hypercholesterolaemia. Eur Heart J 2013, 34:962-971.
11. Cohen J.C., Boerwinkle E., Mosley T.H., Hobbs H.H. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. NEngl J Med 2006, 354:1264-1272.
12. Graham M.J., Lemonidis K.M., Whipple C.P., et al. Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice. JLipid Res 2007, 48:763-767.
13. Wierzbicki A.S., Hardman T.C., Viljoen A. Inhibition of pro-protein convertase subtilisin kexin 9 [corrected] (PCSK-9) as a treatment for hyperlipidaemia. Expert Opin Investig Drugs 2012, 21:667-676.
14. Sjouke B., Kusters D.M., Kastelein J.J., Hovingh G.K. Familial hypercholesterolemia: present and future management. Curr Cardiol Rep 2011, 13:527-536.
15. Ni Y.G., Di M.S., Condra J.H., et al. APCSK9-binding antibody that structurally mimics the EGF(A) domain of LDL-receptor reduces LDL cholesterol invivo. JLipid Res 2011, 52:78-86.
16. Stein E.A., Mellis S., Yancopoulos G.D., et al. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. NEngl J Med 2012, 366:1108-1118.
17. Kosenko T., Golder M., Leblond G., Weng W., Lagace T.A. Low density lipoprotein binds to proprotein convertase subtilisin/kexin type-9 (PCSK9) in Human plasma and inhibits PCSK9-mediated low density lipoprotein receptor degradation. JBiol Chem 2013, 288:8279-8288.
18. Warnakula S., Hsieh J., Adeli K., et al. New insights into how the intestine can regulate lipid homeostasis and impact vascular disease: frontiers for new pharmaceutical therapies to lower cardiovascular disease risk. Can J Cardiol 2011, 27:183-191.