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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2094.)
© 2007 American Heart Association, Inc.

Brief Reviews

New Insights Into the Role of Lipoprotein(a)-Associated Lipoprotein-Associated Phospholipase A₂ in Atherosclerosis and Cardiovascular Disease

Sotirios Tsimikas; Loukas D. Tsironis; Alexandros D. Tselepis

From the Department of Medicine (S.T.), University of California San Diego, La Jolla, Calif; Laboratory of Biochemistry (L.D.T., A.D.T.), Department of Chemistry, University of Ioannina, Ioannina, Greece.

Correspondence to Alexandros D. Tselepis, Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece. E-mail atselep{at}uoi.gr

Lipoprotein(a) [Lp(a)] plays an important role in atherosclerosis. The biological effects of Lp(a) have been attributed either to apolipoprotein(a) or to its low-density lipoprotein-like particle. Lp(a) contains platelet-activating factor acetylhydrolase, an enzyme that exhibits a Ca²⁺-independent phospholipase A₂ activity and is complexed to lipoproteins in plasma; thus, it is also referred to as lipoprotein-associated phospholipase A₂. Substrates for lipoprotein-associated phospholipase A₂ include phospholipids containing oxidatively fragmented residues at the sn-2 position (oxidized phospholipids; OxPLs). OxPLs may play important roles in vascular inflammation and atherosclerosis. Plasma levels of OxPLs present on apolipoprotein B-100 particles (OxPL/apolipoprotein B) are correlated with coronary artery, carotid, and peripheral arterial disease. Furthermore, OxPL/apolipoprotein B levels in plasma are strongly correlated with Lp(a) levels, are preferentially sequestered on Lp(a), and thus are potentially subjected to degradation by the Lp(a)-associated lipoprotein-associated phospholipase A₂. The present review article focuses specifically on the characteristics of the lipoprotein-associated phospholipase A₂ associated with Lp(a) and discusses the possible role of this enzyme in view of emerging data showing that OxPLs in plasma are preferentially sequestered on Lp(a) and may significantly contribute to the increased atherogenicity of this lipoprotein.

Key Words: atherosclerosis • lipoprotein(a) • lipoprotein-associated phospholipase A₂ • oxidized phospholipids • platelet-activating factor acetylhydrolase

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