Circulating autoantibodies to oxidized LDL correlate with impaired coronary endothelial function after cardiac transplantation.
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.


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.
Fang
James C
JC
Cardiovascular Division, Brigham and Women's Hospital, Boston, Mass 02115, USA. jcfang@bics.bwh.harvard.edu
Kinlay
Scott
S
Behrendt
Dominik
D
Hikita
Hiroyuki
H
Witztum
Joseph L
JL
Selwyn
Andrew P
AP
Ganz
Peter
P
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood / Q000209:etiology; D003331:Coronary Vessels / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016014:Linear Models; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D019520:Living Donors; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D005996:Nitroglycerin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects / Q000276:immunology
D001323:Autoantibodies; D007074:Immunoglobulin G; D008055:Lipids; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D005996:Nitroglycerin; D000109:Acetylcholine