Research progress on alternative non-classical mechanisms of PCSK9 in atherosclerosis in patients with and without diabetes.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) acts via a canonical pathway to regulate circulating low-density lipoprotein-cholesterol (LDL-C) via degradation of the LDL receptor (LDLR) on the liver cell surface. Published research has shown that PCSK9 is involved in atherosclerosis via a variety of non-classical mechanisms that involve lysosomal, inflammatory, apoptotic, mitochondrial, and immune pathways. In this review paper, we summarized these additional mechanisms and described how anti-PCSK9 therapy exerts effects through these mechanisms. These additional pathways further illustrate the regulatory role of PCSK9 in atherosclerosis and offer an in-depth interpretation of how the PCSK9 inhibitor exerts effects on the treatment of atherosclerosis.