Statin action enriches HDL3 in polyunsaturated phospholipids and plasmalogens and reduces LDL-derived phospholipid hydroperoxides in atherogenic mixed dyslipidemia

Abstract

Atherogenic mixed dyslipidemia associates with oxidativ stress and defective HDL antioxidative function in metaboli syndrome (MetS). The impact of statin treatment on th capacity of HDL to inactivate LDL-derived, redox-Activ phospholipid hydroperoxides (PCOOHs) in MetS is indeterminate Insulin-resistant, hypertriglyceridemic, hypertensive obese males were treated with pitavastatin (4 mg/day) fo 180 days, resulting in marked reduction in plasma TGs (41% and LDL-cholesterol (r38%), with minor effects on HDLcholestero and apoAI. Native plasma LDL (baseline vs 180 days) was oxidized by aqueous free radicals under mil conditions in vitro either alone or in the presence of the correspondin pre-or poststatin HDL2 or HDL3 at authenti plasma mass ratios. Lipidomic analyses revealed that stati treatment i) reduced the content of oxidizable polyunsaturate phosphatidylcholine (PUPC) species containing DH and linoleic acid in LDL; u) preferentially increased the conten of PUPC species containing arachidonic acid (AA) i small, dense HDL3; iii) induced significant elevation in th content of phosphatidylcholine and phosphatidylethanolamin (PE) plasmalogens containing AA and DHA in HDL3 and iv) induced formation of HDL3 particles with increase capacity to inactivate PCOOH with formation of redoxinactiv phospholipid hydroxide. Statin action attenuate LDL oxidability Concomitantly, the capacity of HDL3 t inactivate redox-Active PCOOH was enhanced relative t HDL2, consistent with preferential enrichment of PE plasmalogen and PUPC in HDL3.