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PCSK9 and atherosclerosis: Looking beyond LDL regulation

Journal

Publisher

WILEY
DOI: 10.1111/eci.13459

Keywords

atherosclerosis; inflammation; low‐ density lipoproteins; Proprotein Convertase Subtilisin; Kexin type 9

Funding

  1. AMGEN [20167781, 2016735982]

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PCSK9 is involved in regulating cholesterol homeostasis and may also be associated with vascular inflammation in atherogenesis. It is expressed by various cell types and detected inside atherosclerotic plaques, potentially playing a role in the molecular processes of atherosclerosis.
Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) is involved in cholesterol homeostasis. After binding to the complex low-density lipoprotein (LDL)-receptor, PCSK9 induces its intracellular degradation, thus reducing serum LDL clearance. In addition to the well-known activity on the hepatic LDL receptor-mediated pathway, PCSK9 has been, however, associated with vascular inflammation in atherogenesis. Indeed, PCSK9 is expressed by various cell types that are involved in atherosclerosis (e.g. endothelial cells, smooth muscle cells and macrophages) and is detected inside human atherosclerotic plaques. We here analyse the biology of PCSK9 and its possible involvement in molecular processes involved in atherosclerosis, beyond the regulation of circulating LDL cholesterol levels.

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