Received on July 29, 2005
Accepted on September 20, 2005

Lipids, Lipoproteins, and Cardiovascular Risk Factors

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

¹ Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece
² Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, Ioannina, Greece

^* To whom correspondence should be addressed. E-mail: atselep{at}cc.uoi.gr.

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.