on July 12, 2007
Published online before print July 12, 2007, doi: 10.1161/01.ATV.0000280571.28102.d4
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Submitted on May 24, 2007
Accepted on June 29, 2007
New Insights Into the Role of Lipoprotein(a)-Associated Lipoprotein-Associated Phospholipase A2 in Atherosclerosis and Cardiovascular Disease
Sotirios Tsimikas ;
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.
* To whom correspondence should be addressed. E-mail: atselep{at}uoi.gr.
Abstract--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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