• Baohai Shao, Chongren Tang, Abhishek Sinha, Philip S Mayer, George D Davenport, Nathan Brot, Michael N Oda, Xue-Qiao Zhao, and Jay W Heinecke.
• From the Department of Medicine, University of Washington, Seattle (B.S., C.T., A.S., P.S.M., G.D.D., X.-Q.Z., J.W.H.); Diabetes and Obesity Center of Excellence, University of Washington, Seattle (B.S, C.T., P.S.M., J.W.H.); Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY (N.B.); Center for Molecular Biology and Biotechnology, Florida Atlantic University, Jupiter (N.B.); and Children's Hospital Oakland Research Institute, CA (M.N.O.). bhshao@u.washington.edu.
• Circ. Res. 2014 May 23; 114 (11): 1733-42.

RationaleThe efflux capacity of high-density lipoprotein (HDL) with cultured macrophages associates strongly and negatively with coronary artery disease status, indicating that impaired sterol efflux capacity might be a marker-and perhaps mediator-of atherosclerotic burden. However, the mechanisms that contribute to impaired sterol efflux capacity remain poorly understood.ObjectiveOur aim was to determine the relationship between myeloperoxidase-mediated oxidative damage to apolipoprotein A-I, the major HDL protein, and the ability of HDL to remove cellular cholesterol by the ATP-binding cassette transporter A1 (ABCA1) pathway.Methods And ResultsWe quantified both site-specific oxidation of apolipoprotein A-I and HDL's ABCA1 cholesterol efflux capacity in control subjects and subjects with stable coronary artery disease or acute coronary syndrome. Subjects with coronary artery disease and acute coronary syndrome had higher levels of chlorinated tyrosine 192 and oxidized methionine 148 compared with control subjects. In contrast, plasma levels of myeloperoxidase did not differ between the groups. HDL from the subjects with coronary artery disease and acute coronary syndrome was less able to accept cholesterol from cells expressing ABCA1 compared with HDL from control subjects. Levels of chlorinated tyrosine and oxidized methionine associated inversely with ABCA1 efflux capacity and positively with atherosclerotic disease status. These differences remained significant after adjusting for HDL-cholesterol levels.ConclusionsOur observations indicate that myeloperoxidase may contribute to the generation of dysfunctional HDL with impaired ABCA1 efflux capacity in humans with atherosclerosis. Quantification of chlorotyrosine and oxidized methionine in circulating HDL might be useful indicators of the risk of cardiovascular disease that are independent of HDL-cholesterol.© 2014 American Heart Association, Inc.

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