Examining the Role of Lipoprotein‐Associated Phospholipase A2 in Atherosclerosis

Abstract

Interest in the enzyme Lipoprotein Associated Phospholipase A2 (Lp‐PLA2) emerged when it was recognized to be elevated in patients at risk for developing atherosclerosis. Lp‐PLA2 exists in human plasma on the membrane of lipoproteins, and preliminary investigations indicate that the physiological effect of Lp‐PLA2 is dependent on the lipoprotein to which it is coupled— namely, that the enzyme has a protective effect when it is on the surface of High Density Lipoproteins (HDL) and is atherogenic when on the surface of Low Density Lipoproteins (LDL). This project aims to develop and employ an assay for the investigation of factors that perturb the distribution of Lp‐PLA2 between lipoproteins, identifying correlations between its location and its role in human health. To analyze Lp‐PLA2 distribution, lipoproteins are separated using electrophoresis in custom designed non‐denaturing poly‐acrylamide gels. Separation of lipoproteins by native electrophoresis has been done previously, and a modification of this method is employed for a cost‐efficient approach that causes LDL and HDL to form discrete bands, allowing for quantification of Lp‐PLA2 in each. By increasing our understanding of the function of Lp‐PLA2 we have the ability to improve current models, aiding in the future development of improved treatments for atherosclerosis.