Expanding Biology of PCSK9: Roles in Atherosclerosis and Beyond

Curr Atheroscler Rep. 2022 Jul 29. doi: 10.1007/s11883-022-01057-z. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: Since the discovery of PCSK9 in 2003, this proprotein convertase was shown to target specific receptors for degradation in endosomes/lysosomes, including LDLR and other family members and hence to enhance the levels of circulating LDL-cholesterol (LDLc). Accordingly, inhibitors of PCSK9, including monoclonal antibodies blocking its circulating activity and siRNA silencers of its hepatic expression, are now used in clinics worldwide to treat hypercholesterolemia patients effectively and safely in combination with statins and/or ezetimibe. These powerful treatments reduce the incidence of atherosclerosis by at least 20%. Since 2008, novel targets of PCSK9 began to be defined, thereby expanding its roles beyond LDLc regulation into the realm of inflammation, pathogen infections and cellular proliferation in various cancers and associated metastases.RECENT FINDINGS: Some pathogens such as dengue virus exploit the ability of PCSK9 to target the LDLR for degradation to enhance their ability to infect cells. Aside from increasing the degradation of the LDLR and its family members VLDLR, ApoER2 and LRP1, circulating PCSK9 also reduces the levels of other receptors such as CD36 (implicated in fatty acid uptake), oxidized LDLR receptor (that clears oxidized LDLc) as well as major histocompatibility class-I (MHC-I) receptors (implicated in the immune response to antigens)...
Source: Atherosclerosis - Category: Cardiology Authors: Source Type: research