PCSK9 with a gain of function D374Y mutation aggravates atherosclerosis by inhibiting PPARα expression.

The preprotein convertase, Bacillus subtilis protease/kexin type 9 serine protease (PCSK9), has garnered significant attention as a potential lipid lowering and therapeutic drug target for atherosclerosis (AS). Peroxisome proliferator-activated receptor alpha (PPARα) is expressed in various tissues and has crucial roles in lipid metabolism and the inflammatory response; however, the precise impact of PCSK9 on AS progression through its regulation of PPARα remains uncertain. The present study aimed to examine the impact of introducing stable liver transduction of human derived PCSK9 with a gain of function D374Y mutation (PCSK9) into systemic PPARα knockout mice (PPARα) on plasma lipid levels and AS.