on October 10, 2002
Published online before print October 10, 2002, doi: 10.1161/01.ATV.0000040854.47020.44
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Submitted on July 22, 2002
Accepted on September 23, 2002
Circulating Autoantibodies to Oxidized LDL Correlate With Impaired Coronary Endothelial Function After Cardiac Transplantation
James C. Fang *;
From the Cardiovascular Division (J.C.F., S.K., D.B., H.H., A.P.S., P.G.), Brigham and Women's Hospital, Boston, Mass, and the Division of Endocrinology and Metabolism (J.L.W.), University of California at San Diego, La Jolla.
* To whom correspondence should be addressed. E-mail: jcfang{at}bics.bwh.harvard.edu.
Objective—The oxidative modification of low density lipoprotein (LDL) may play a role in the pathogenesis of transplant-associated arteriosclerosis. Oxidized LDL (OxLDL) is immunogenic as well as atherogenic, and the level of autoantibodies to OxLDL has been taken as an index of the oxidant state of LDL. Because endothelial dysfunction is key in the initiation of transplant-associated arteriosclerosis, we postulated that the level of OxLDL autoantibody is associated with the degree of impairment of coronary endothelial function.
Methods and Results—Coronary endothelium-dependent dilation was assessed by using intracoronary acetylcholine and endothelium-independent dilation by nitroglycerin in 36 cardiac transplant recipients within 1 year of transplantation. The coronary responses to acetylcholine ranged from -37% (vasoconstriction) to 31% (vasodilation), and the responses to nitroglycerin ranged from 0% to 42% (vasodilation). The coronary vasomotor response to acetylcholine was significantly and inversely related to OxLDL autoantibody levels (r=-0.43, P<0.01) but not LDL levels (r=-0.04, P=0.83) or circulating OxLDL levels detected by monoclonal antibody EO6 (r=-0.27, P=0.11). The coronary artery response to nitroglycerin was not related to levels of OxLDL autoantibodies, LDL, or EO6 (all P=NS).
Conclusions—Autoantibodies to OxLDL are increased in patients with coronary endothelial dysfunction in the first year after cardiac transplantation. The oxidative modification of LDL by inducing endothelial dysfunction in cardiac transplant recipients may be a critical step in the atherogenic effects of LDL and may provide a potential target for therapy.
Key words: arteriosclerosis • transplantation • endothelium • oxidized LDL
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