Lipoprotein-associated phospholipase A2 protein expression in the natural progression of human coronary atherosclerosis

Objective - Although lipoprotein- associated phospholipase A(2) ( Lp- PLA(2)) has received recent attention as a biomarker of inflammation and risk for acute coronary events, its relative expression in coronary plaque phenotypes, including unstable lesions, has not been established. Methods and Results - Coronary segments ( n= 30) were prospectively collected from 25 sudden coronary death patients for immunolocalization of Lp- PLA(2). Lesion morphologies were classified as pathologic intimal thickening, fibroatheromas, thin-cap fibroatheromas ( fibrous cap thicknesses < 65 mu m), and rupture. The expression of Lp- PLA(2) was detected using a specific monoclonal antibody. Apoptosis was identified by DNA end- labeling using terminal deoxynucleotidyl transferase ( TdT). Lp- PLA(2) staining in early plaques was absent or minimally detected. In contrast, thin-cap fibroatheromas and ruptured plaques showed intense Lp- PLA(2) expression within necrotic cores and surrounding macrophages including those in the fibrous cap. The degree of macrophage apoptosis was greater in thin-cap fibroatheroma and ruptures compared with less advanced plaques with additional double labeling studies showing Lp- PLA(2) present in apoptotic cells in regions of high macrophage density. Conclusions - Lp- PLA(2) is strongly expressed within the necrotic core and surrounding macrophages of vulnerable and ruptured plaques, with relatively weak staining in less advanced lesions. These findings together with the association of Lp- PLA(2) in apoptotic macrophages suggest a potential role in promoting plaque instability.