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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2523.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Lipoprotein-Associated Phospholipase A₂ Protein Expression in the Natural Progression of Human Coronary Atherosclerosis

Frank D. Kolodgie; Allen P. Burke; Kristi S. Skorija; Elena Ladich; Robert Kutys; Addisalem Taye Makuria; Renu Virmani

From CVPath Institute, Inc (F.D.K., A.P.B., K.S.S., E.L., R.K., R.V.), Gaithersburg, Md; and the Department of Pathology (A.T.M.), Georgetown University, Washington, DC.

Correspondence to Renu Virmani, MD, Medical Director, CVPath Institute Inc, 19 Firstfield Road, Gaithersburg, MD 20878. 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.

The expression of lipoprotein-associated phospholipase A₂ (Lp-PLA₂) was assessed in early through late, unstable coronary plaques from sudden death victims. Lp-PLA₂ was mostly present in plaque ruptures and thin-cap fibroatheromas in necrotic cores and surrounding areas of apoptotic macrophages. The present study suggests Lp-PLA₂ may be an important biomarker for plaque instability.

Key Words: lipoprotein-associated phospholipase A₂ • sudden coronary death • plaque rupture • apoptosis • cardiovascular risk

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Lipoprotein-Associated Phospholipase A₂: Novel Biomarker and Causal Mediator of Atherosclerosis?

Nancy Swords Jenny
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