Journal of the Practice of Cardiovascular Sciences

REVIEW ARTICLE
Year
: 2020  |  Volume : 6  |  Issue : 3  |  Page : 226--233

PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9): A Narrative Review


Pamila Dua, KH Reeta 
 Department of Pharmacology, AIIMS, New Delhi, India

Correspondence Address:
Dr. Pamila Dua
BK2/27, Shalimar Bagh, New Delhi - 110 088
India

Coronary artery disease (CAD), the most common type of heart disease, is the leading reason for mortality in both developing and developed countries. Increased cholesterol and fatty deposits (called plaques) may cause hardening or narrowing of the arteries which supply blood to heart muscles. Triglycerides, low density lipoproteins (LDL), high density lipoproteins (HDL) are different types of cholesterols found in the blood and LDL is the main target for lipid modifying therapy, with the aim of improving long term CAD prognosis. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is one of the candidate genes with expression of PCSK9 protein and PCSK9 inhibitors are coming up as newer lipid lowering therapy. This narrative review highlights the journey of drug development from recognition of PCSK9 gene to the recent approvals of PCSK9 targeting LDL lowering pharmacotherapy. A bibliographic survey was made with titles PCSK9, PCSK9 inhibitors and coronary artery disease in different search engines from year 2000 to 2019 and filtered with review, preclinical and clinical studies. Retrieved articles were revisited and it was observed that PCSK9 is expressed mainly in hepatocytes and to some extent in mesenchymal cells of kidney, intestinal ileum, colon epithelia and in telencephalon neurons of embryonic brain. In hepatocytes, loss-of function mutations of PCSK9 leads to higher levels of LDL receptors. These receptors make LDL receptor-LDL cholesterol complex, which is directed to the lysosome for degradation of LDL in hepatocytes and lowers LDL cholesterol levels, ultimately resulting in protection from CAD. Gain-of-function mutations hamper LDL degradation. PCSK9 research has proposed an exciting new area for cholesterol management and CAD risk reduction. Different PCSK9 inhibitors with different therapeutic targets for CAD are evolving day by day from bench to bedside. This review could be valuable for helping researchers acquire a deeper insight for PCSK9 and its Inhibitors.


How to cite this article:
Dua P, Reeta K H. PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9): A Narrative Review.J Pract Cardiovasc Sci 2020;6:226-233


How to cite this URL:
Dua P, Reeta K H. PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9): A Narrative Review. J Pract Cardiovasc Sci [serial online] 2020 [cited 2021 Oct 16 ];6:226-233
Available from: https://www.j-pcs.org/article.asp?issn=2395-5414;year=2020;volume=6;issue=3;spage=226;epage=233;aulast=Dua;type=0