Dimitri Patriki, Seyed Soheil Saeedi Saravi, Giovanni G. Camici, Luca Liberale and Jürg H. Beer* Pages 251 - 267 ( 17 )
Proprotein convertase subtilisin/Kexin 9 (PCSK 9) is revealed to be a key player in lipid metabolism and, therefore, in the development and progression of atherosclerosis. PCSK 9 binds to the low-density lipoprotein (LDL) receptor, induces its degradation, and increases circulating blood LDL. As a result, PCSK 9 inhibitors represent an essential pillar in cardiovascular risk reduction therapies due to their highly sufficient LDL decreasing properties. While the influence of PCSK 9 on lipid metabolism has been widely investigated, the full pathophysiological spectrum of PCSK 9 is yet to be determined. Statins have already been demonstrated to have beneficial anti-inflammatory effects. In this context, evidence suggests that PCSK 9 also interferes with inflammatory processes, thereby contributing to the development of atherosclerosis. As lipid metabolism on its own affects inflammatory processes, it is difficult to distinguish between lipid-dependent and -independent inflammatory properties of PCSK 9. A body of evidence has revealed that PCSK9 LDL-independently regulates the secretion of pro-inflammatory cytokines and inflammation-underlying pathways in vascular walls, whereas recent observations suggest that PCSK9 also interacts with lectin-like oxidized LDL receptor-1 (LOX-1) and dampens inflammatory responses through LDL reduction. In conclusion, this review provides mounting evidence indicating how PCSK9 promotes vascular inflammation and subsequent atherosclerosis to shed light on the anti-inflammatory effects of PCSK9 inhibitors in the prevention of atherosclerosis.
PCSK9, inflammation, lipid, LDL, atherosclerosis, cardiovascular disease.
Department of Medicine, Cantonal Hospital Baden, 5404 Baden, Department of Medicine, Cantonal Hospital Baden, 5404 Baden, Center for Molecular Cardiology, University of Zurich, 8952 Schlieren, Center for Molecular Cardiology, University of Zurich, 8952 Schlieren, Department of Medicine, Cantonal Hospital Baden, 5404 Baden