Perkembangan Implikasi Biologi dan Klinis Proprotein Convertase Subtilisin-Kexin 9


Pada tahun 2003 Proprotein Convertase Subtilisin-Kexin 9 (PCSK9) berhasil diidentifikasi.1 PCSK9 berfungsi meningkatkan kadar LDL Cholesterol (LDL-C) melalui degradasi LDL Receptor (LDLR).2 Penemuan PCSK9 telah merevolusi serta merupakan perkembangan terpenting pada bidang riset kardiovaskular satu dekade terakhir, terutama dalam regulasi LDL-C. 1


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1. Seidah, Nabil G. New Developments in proprotein convertase subtilisin–kexin 9’s biology and clinical implications. Curr Opin Lipidol. 2016;27:274-81.

2. 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;279:48865–75.

3. Chan JC, Piper DE, Cao Q, et al. A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates. Proc Natl Acad Sci USA. 2009;106:9820–5.

4. Stein EA, Raal F. Reduction of low-density lipoprotein cholesterol by monoclonal antibody inhibition of PCSK9. Annu Rev Med. 2014;65:417–31.

5. Seidah NG, Awan Z, Chretien M, Mbikay M. PCSK9: A key modulator of cardiovascular health. Circ Res. 2014;114:1022–36.

6. Sabatine MS, Giugliano RP, Wiviott SD, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1500–9.

7. Galabova G, Brunner S, Winsauer G, et al. Peptide-based anti-PCSK9 vaccines—An approach for long-term LDLc management.PLoS One. 2014;9:e114469.

8. Demers A, Samani S, Lauzier B, et al. PCSK9 induces CD36 degradation and affects long-chain fatty acid uptake and triglyceride metabolism in adipocytes and in mouse liver. Arterioscler Thromb Vasc Biol. 2015;35:2517–25.

9. Stein EA, Giugliano RP, Koren MJ, et al. Efficacy and safety of evolocumab (AMG 145), a fully human monoclonal antibody to PCSK9, in hyperlipidaemic patients on various background lipid therapies: pooled analysis of 1359 patients in four phase 2 trials. Eur Heart J. 2014;35:2249–59.

10. Roubtsova A, Chamberland A, Marcinkiewicz J, et al. PCSK9 deficiency unmasks a sex/tissue-specific subcellular distribution of the LDL and VLDL receptors in mice. J Lipid Res. 2015;56:2133–42.

11. Konarzewski M, Szolkiewicz M, Sucajtys-Szulc E, et al. Elevated circulating PCSK-9 concentration in renal failure patients is corrected by renal replacement therapy. Am J Nephrol. 2014;40:157–63.

12. Gaieski DF, Edwards JM, Kallan MJ, Carr BG. Benchmarking the incidence and mortality of severe sepsis in the United States. Crit Care Med. 2013;41:1167–74.
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Perkembangan Implikasi Biologi dan Klinis Proprotein Convertase Subtilisin-Kexin 9. (2017). Indonesian Journal of Cardiology, 37(3), 117-121.