Lipoprotein-Associated Phospholipase A2 Activity Is a Marker of Small, Dense LDL Particles in Human Plasma

Abstract

Background: Recent clinical studies showed that lipoprotein-associated phospholipase A2 (Lp-PLA2) is a predictor for incident atherosclerotic disease. We have previously shown that among the LDL subfractions, Lp-PLA2 activity is preferentially associated with the atherogenic small, dense (sdLDL) particles in vitro. We investigated whether Lp-PLA2 could be a marker of sdLDL in human plasma. Methods: One hundred and seventy-six individuals participated in the study. LDL subclass analysis was performed by polyacrylamide gel electrophoresis. Lp-PLA2 activity and mass were determined in total plasma and in apolipoprotein B-depleted plasma (HDL-Lp-PLA2). Non–HDL-Lp-PLA2 activity and mass were calculated by subtracting the HDL-Lp-PLA2 from total plasma Lp-PLA2. Results: On the basis of the LDL subclass analysis, participants were categorized into phenotype A and non-A (total cholesterol mass of the sdLDL subfractions ≤0.155 and >0.155 mmol/L, respectively). Unlike total plasma Lp-PLA2 mass, total plasma Lp-PLA2 activity and non–HDL-Lp-PLA2 activity and mass were significantly higher in persons with phenotype non-A compared with persons with phenotype A, whereas HDL-Lp-PLA2 activity and mass were lower in persons with phenotype non-A compared with phenotype A. Total plasma activity and non–HDL-Lp-PLA2 activity and mass, but not Lp-PLA2 mass, were correlated with sdLDL-cholesterol mass, proportion, and mean LDL particle size. In multiple regression analysis, total plasma and non–HDL-Lp-PLA2 activities were the second best predictors of the presence of sdLDL particles in human plasma after serum triglyceride concentrations. At serum triglyceride concentrations >1.356 mmol/L, total plasma and non–HDL-Lp-PLA2 activity added significantly to the prediction of the presence of sdLDL in plasma. Conclusions: Lp-PLA2 activity, but not the enzyme mass, is a marker of sdLDL in human plasma.