Antioxidative activity of HDL particle subspecies is impaired in hyperalphalipoproteinemia: Relevance of enzymatic and physicochemical properties

Objective - Hyperalphalipoproteinemia (HALP) is characterized by elevated plasma levels of high-density lipoprotein (HDL) particles with altered composition, metabolism, and function. The impact of such modification on antioxidative activities of HDL subfractions is indeterminate. Methods and Results - Gradient fractionation revealed that buoyant HDL2b and 2a and small dense HDL3b and 3c levels were elevated up to 2.0-fold in HALP subjects ( n = 9; mean plasma HDL cholesterol, 79 mg/dL) with low hepatic lipase activity. HDL2a, 3a, 3b, and 3c displayed lower specific antioxidative activity (sAA) during low-density lipoprotein (LDL) oxidation ( - 15% to - 86%, on a unit particle mass basis) than their normolipidemic counterparts ( n = 13). LDL oxidation was delayed by control HDL3a, 3b, and 3c ( up to - 79%) but specifically by HDL3c ( - 54%) in HALP. Paraoxonase activity was deficient in all HALP HDL subfractions. Paraoxonase, PAF-AH, and LCAT activities together accounted for approximate to 50% of variation in sAA. Abnormal chemical composition of HDL3b and 3c (cholesterol-deficient, triglyceride-enriched) in HALP was associated with impaired sAA. Systemic oxidative stress ( as plasma 8-isoprostanes) tended to be elevated (1.5-fold) in HALP and negatively correlated with sAA ( as TBARS). Conclusions - Intrinsic antioxidative activity of HDL subspecies is impaired in HALP, reflecting altered enzymatic and physicochemical properties.