on September 7, 2006
Published online before print September 7, 2006, doi: 10.1161/01.ATV.0000244681.72738.bc
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Submitted on July 7, 2006
Accepted on August 25, 2006
Lipoprotein-Associated Phospholipase A2 Protein Expression in the Natural Progression of Human Coronary Atherosclerosis
Frank D. Kolodgie ;
From CVPath, International Registry of Pathology (F.D.K., A.P.B., K.S.S., E.L., R.K., A.T.M., R.V.), Gaithersburg, Md; and the Department of Pathology (A.T.M.), Georgetown University, Washington, DC.
* To whom correspondence should be addressed. E-mail: rvirmani{at}cvpath.org.
Objective-- Although lipoprotein-associated phospholipase A2 (Lp-PLA2) 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-PLA2. Lesion morphologies were classified as pathologic intimal thickening, fibroatheromas, thin-cap fibroatheromas (fibrous cap thicknesses <65 µm), and rupture. The expression of Lp-PLA2 was detected using a specific monoclonal antibody. Apoptosis was identified by DNA end-labeling using terminal deoxynucleotidyl transferase (TdT). Lp-PLA2 staining in early plaques was absent or minimally detected. In contrast, thin-cap fibroatheromas and ruptured plaques showed intense Lp-PLA2 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-PLA2 present in apoptotic cells in regions of high macrophage density.
Conclusions--Lp-PLA2 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-PLA2 in apoptotic macrophages suggest a potential role in promoting plaque instability.
Key words: lipoprotein-associated phospholipase A2 • sudden coronary death • plaque rupture • apoptosis • cardiovascular risk
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