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

Duality of statin action on lipoprotein subpopulations in the mixed dyslipidemia of metabolic syndrome: Quantity vs quality over time and implication of CETP

“…Details of the clinical protocol, the patient cohort, and comprehensive inclusion and exclusion criteria have been reported previously. [47][48][49] Briefly, the CAPITAIN Study (Chronic and Acute effects of PITAvastatIN on monocyte phenotype, endothelial function, and HDL atheroprotective function in patients with MetS; ClinicalTrials.gov: NCT01595828; see Supplementary Fig. S1 for study design) recruited 12 Caucasian male subjects (mean age: 50 6 3 years; body mass index: 31.7 6 0.5 kg/m 2 ; waist circumference: 110 6 3 cm) who displayed the risk factor cluster of MetS diagnosed strictly according to International Diabetes Federation criteria.…”

“…Despite the extensive statin literature, however, the dynamic, integrated, temporal relationships between the quantity and quality of lipoprotein subpopulations in the mixed dyslipidemia of MetS under statin treatment remain largely indeterminate. 21,[29][30][31][36][37][38][39][40][41][42][43][44][45][46][47][48] We evaluated these relationships in a small, extensively phenotyped cohort of obese males with a highly defined prediabetic, mixed dyslipidemia and moderate insulin resistance at elevated cardiovascular risk in the CAPITAIN study over a time course of 6 months; pitavastatin (daily dose 4 mg/d) was selected as a model statin in part as evidence has progressively emerged attesting to the neutrality of pitavastatin on glucose homeostasis. 30,31,37,41,[47][48][49][50][51] This approach allowed us to evaluate 3 key questions: (1) Do the quantitative and qualitative modifications of lipoprotein particle subpopulations induced by statin action follow the same dynamic time course?…”

【Original Contribution】 Plasma and Erythrocyte Membrane Plasmalogen Diminished in Severe Atherosclerotic Patients Undergoing Endovascular Therapy

“…The effects of statin on the plasma concentrations of plasmalogen are conflicting. In literature, pitavastatin treatment (4 mg/day) resulted in marked reduction in plasma LDL cholesterol, preferential increase in pl-PC and pl-PE and minor effects on HDL cholesterol 19) , whereas rosvastatin treatment (10 or 40 mg/day) significantly reduced the plasma levels of total cholesterol, LDL cholesterol, triglyceride, SM, PC, pl-PC and pl-PE 20) .…”

“…of statin, i.e., dose of statin prescribed in Japanese is lower than that in westerners 19,20) . Although possible therapeutic effects of statin on our data remain, reduced plasma concentrations of plasmalogens in severely atherosclerotic patients are reported in literature, and our data (Table 1) are compatible to literature 21,22) .…”

Extrinsic effectors regulating genes for plasmalogen biosynthetic enzymes in HepG2 cells

“…Pitavastatin is a strong HMG-CoA reductase inhibitor and is more potent than other statins in lowering serum total cholesterol, low-density lipoprotein cholesterol, and triglycerides with modest elevation of HDL cholesterol [35]. Recently, pitavastatin was reported to increase Pl content in HDL particles in relation to improving HDL functionality [36]. Moreover, pitavastatin promoted the expression of HDL metabolism-associated proteins such as APOA1.…”