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The role of oxidized phospholipids in mediating lipoprotein(a) atherogenicity

Tsimikas, Sotirios; Witztum, Joseph L

doi: 10.1097/MOL.0b013e328308b622
Hyperlipidaemia and cardiovascular disease: Edited by Paul N. Durrington

Purpose of review To review emerging data on the relationship between lipoprotein(a) and oxidized phospholipids.

Recent findings We have recently proposed that a unique physiological role of lipoprotein(a) may be to bind and transport proinflammatory oxidized phospholipids and that this interaction may mediate a common biological influence on cardiovascular disease. In a large series of clinical studies performed to date, a very strong correlation was found between plasma levels of lipoprotein(a) and the content of oxidized phospholipids on apolipoprotein B-100 particles (OxPL/apoB), measured by monoclonal antibody E06, which binds the phosphocholine head group of oxidized phospholipids but not native phospholipids. The correlation of OxPL/apoB to lipoprotein(a) is very strong in individuals with small apolipoprotein(a) isoforms (r = ∼0.95) and modest in individuals with large isoforms (r = ∼0.60). In-vitro studies have demonstrated that the vast majority of oxidized phospholipids detected by E06 are bound to lipoprotein(a) in human plasma. A similarly strong association with oxidized phospholipids was also documented in transgenic mice overexpressing lipoprotein(a), even in mice not fed atherogenic diets or with overt atherosclerosis.

Summary A better understanding of the ability of human lipoprotein(a) to bind oxidized phospholipids may allow clinically important insights into the role of oxidized phospholipids and lipoprotein(a) in human atherogenesis and cardiovascular disease and may provide novel diagnostic tools and therapeutic interventions aimed at measuring and treating elevated levels of OxPL/apoB and lipoprotein(a).

Department of Medicine, University of California, San Diego, California, USA

Correspondence to Sotirios Tsimikas, MD, Vascular Medicine Program, University of California San Diego, 9350 Campus Point Drive, Cardiovascular Diseases, La Jolla, CA 92037-0975, USA Tel: +1 8585346109; fax: +1 8585342005; e-mail: stsimikas@ucsd.edu

© 2008 Lippincott Williams & Wilkins, Inc.