Can phosphatidylserine enhance atheroprotective activities of high-density lipoprotein?

Although high-density lipoprotein (HDL) is well known to be protective against atherosclerotic cardiovascular disease, therapeutic interventions to raise HDL-cholesterol levels do not translate into reduction in cardiovascular risk. Due to the compositional complexity of HDL particles, molecular determinants of their atheroprotective function still remain to be clarified. Recent structural and functional data identify phospholipid as a major bioactive component of HDL. Such a role has recently been specifically evidenced for phosphatidylserine (PS); indeed, HDL content of PS displayed positive correlations with all metrics of HDL functionality assessed. This review summarizes current knowledge about HDL-associated PS; possible mechanisms for its atheroprotective role are discussed and potential applications of PS to HDL-based therapies are highlighted.