Regulation of Platelet Function by HDL

Over the past decade, increasing the capacity of HDL (high-density lipoprotein) cholesterol to mediate macrophage reverse cholesterol transport has been a target of interest in the treatment of cardiovascular diseases (CVDs). However, clinical studies reporting the limited efficacy of HDL or its main apolipoprotein, APOA1, in reducing cardiovascular events have emerged. Although HDL cholesterol is unlikely to play a direct causal role in CVD, its inverse, albeit modest, association with CVD risk, consistently observed in large population studies, suggests it may influence alternative pathways beyond cholesterol metabolism. Given the diverse functions of HDL and its components, it is conceivable that its impact on CVD occurs through less direct mechanisms. A potential hypothesis is that HDL modulates platelet function, a crucial player in the initiation and progression of atherothrombosis, which may contribute to its observed relationship with CVD risk. In this review, we focus on how HDL and its components, with an emphasis on APOA1, interact with platelets (and their precursors or activation products) to modulate atherothrombotic responses.