The PCSK9 Revolution and the Potential of PCSK9-based Therapies to Reduce LDL-cholesterol

Overview

Journal Glob Cardiol Sci Pract

Specialty Cardiology & Vascular Diseases

Date 2017 Oct 4

PMID 28971102

Citations 28

Authors

Nabil G Seidah

Affiliations

Soon will be listed here.

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References

Awan Z, Denis M, Roubtsova A, Essalmani R, Marcinkiewicz J, Awan A . Reducing Vascular Calcification by Anti-IL-1β Monoclonal Antibody in a Mouse Model of Familial Hypercholesterolemia. Angiology. 2015; 67(2):157-67. DOI: 10.1177/0003319715583205. View

Duff C, Scott M, Kirby I, Hutchinson S, Martin S, Hooper N . Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor. Biochem J. 2009; 419(3):577-84. PMC: 2669217. DOI: 10.1042/BJ20082407. View

Singh S, Bittner V . Familial hypercholesterolemia--epidemiology, diagnosis, and screening. Curr Atheroscler Rep. 2015; 17(2):482. DOI: 10.1007/s11883-014-0482-5. View

Van de Ven W, Voorberg J, Fontijn R, Pannekoek H, van den Ouweland A, van Duijnhoven H . Furin is a subtilisin-like proprotein processing enzyme in higher eukaryotes. Mol Biol Rep. 1990; 14(4):265-75. DOI: 10.1007/BF00429896. View

Maxwell K, Breslow J . 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(18):7100-5. PMC: 406472. DOI: 10.1073/pnas.0402133101. View

Dong B, Singh A, Azhar S, Seidah N, Liu J . High-fructose feeding promotes accelerated degradation of hepatic LDL receptor and hypercholesterolemia in hamsters via elevated circulating PCSK9 levels. Atherosclerosis. 2015; 239(2):364-74. PMC: 4523098. DOI: 10.1016/j.atherosclerosis.2015.01.013. View

Sun X, Essalmani R, Day R, Khatib A, Seidah N, Prat A . Proprotein convertase subtilisin/kexin type 9 deficiency reduces melanoma metastasis in liver. Neoplasia. 2013; 14(12):1122-31. PMC: 3540939. DOI: 10.1593/neo.121252. View

McNutt M, Lagace T, Horton J . Catalytic activity is not required for secreted PCSK9 to reduce low density lipoprotein receptors in HepG2 cells. J Biol Chem. 2007; 282(29):20799-803. DOI: 10.1074/jbc.C700095200. View

Seidah N, Awan Z, Chretien M, Mbikay M . PCSK9: a key modulator of cardiovascular health. Circ Res. 2014; 114(6):1022-36. DOI: 10.1161/CIRCRESAHA.114.301621. View

10.

Butkinaree C, Canuel M, Essalmani R, Poirier S, Benjannet S, Asselin M . Amyloid Precursor-like Protein 2 and Sortilin Do Not Regulate the PCSK9 Convertase-mediated Low Density Lipoprotein Receptor Degradation but Interact with Each Other. J Biol Chem. 2015; 290(30):18609-20. PMC: 4513119. DOI: 10.1074/jbc.M115.647180. View

11.

Ding Q, Strong A, Patel K, Ng S, Gosis B, Regan S . Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing. Circ Res. 2014; 115(5):488-92. PMC: 4134749. DOI: 10.1161/CIRCRESAHA.115.304351. View

12.

Galabova G, Brunner S, Winsauer G, Juno C, Wanko B, Mairhofer A . Peptide-based anti-PCSK9 vaccines - an approach for long-term LDLc management. PLoS One. 2014; 9(12):e114469. PMC: 4256444. DOI: 10.1371/journal.pone.0114469. View

13.

Chretien M, Li C . Isolation, purification, and characterization of gamma-lipotropic hormone from sheep pituitary glands. Can J Biochem. 1967; 45(7):1163-74. DOI: 10.1139/o67-133. View

14.

Mitchell T, Chao G, Sitkoff D, Lo F, Monshizadegan H, Meyers D . Pharmacologic profile of the Adnectin BMS-962476, a small protein biologic alternative to PCSK9 antibodies for low-density lipoprotein lowering. J Pharmacol Exp Ther. 2014; 350(2):412-24. DOI: 10.1124/jpet.114.214221. View

15.

Lagace T, Curtis D, Garuti R, McNutt M, Park S, Prather H . Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice. J Clin Invest. 2006; 116(11):2995-3005. PMC: 1626117. DOI: 10.1172/JCI29383. View

16.

Zhang Y, Eigenbrot C, Zhou L, Shia S, Li W, Quan C . Identification of a small peptide that inhibits PCSK9 protein binding to the low density lipoprotein receptor. J Biol Chem. 2013; 289(2):942-55. PMC: 3887217. DOI: 10.1074/jbc.M113.514067. View

17.

Abifadel M, Varret M, Rabes J, Allard D, Ouguerram K, Devillers M . Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003; 34(2):154-6. DOI: 10.1038/ng1161. View

18.

da Palma J, Burri D, Oppliger J, Salamina M, Cendron L, Polverino de Laureto P . Zymogen activation and subcellular activity of subtilisin kexin isozyme 1/site 1 protease. J Biol Chem. 2014; 289(52):35743-56. PMC: 4276844. DOI: 10.1074/jbc.M114.588525. View

19.

Abifadel M, Elbitar S, Khoury P, Ghaleb Y, Chemaly M, Moussalli M . Living the PCSK9 adventure: from the identification of a new gene in familial hypercholesterolemia towards a potential new class of anticholesterol drugs. Curr Atheroscler Rep. 2014; 16(9):439. DOI: 10.1007/s11883-014-0439-8. View

20.

Mizuno K, Nakamura T, Ohshima T, Tanaka S, Matsuo H . Yeast KEX2 genes encodes an endopeptidase homologous to subtilisin-like serine proteases. Biochem Biophys Res Commun. 1988; 156(1):246-54. DOI: 10.1016/s0006-291x(88)80832-5. View