PCSK9 and atherosclerosis: Looking beyond LDL regulation

This is the unformatted version of the accepted review paper manuscript "PCSK9 and atherosclerosis: Looking beyond LDL regulation" published on Eur J Clin Invest. 2021 Apr;51(4):e13459, byRagusa R, Basta G, Neglia D, De Caterina R, Del Turco S, Caselli C.

Abstract 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.