Apolipoprotein C-III in atherosclerosis: from pathophysiological mechanisms to translational therapeutics

Apolipoprotein C-III (apoC-III) has emerged as a pivotal therapeutic target for lipid-lowering therapies, particularly for hypertriglyceridemia. However, its broader implications in the pathogenesis of atherosclerosis remain to be fully elucidated. ApoC-III is extensively studied for its classical role in modulating lipoprotein lipase activity; nevertheless, recent evidence highlights its multifaceted mechanisms involving the regulation of remnant cholesterol clearance, low-density lipoprotein subfraction transformation, high-density lipoprotein functionality, and inflammasome activation. Meanwhile, the emergence of novel APOC3 gene-edited models beyond murine systems has provided indispensable perspectives for deciphering the complex links between apoC-III and atherogenesis. Therefore, this review aims to comprehensively summarize the translational research surrounding apoC-III, from its central function in lipoprotein metabolism to its critical lipoprotein lipase-independent effects, offering a promising outlook for the clinical management of atherosclerotic cardiovascular disease.