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Blood, 15 January 2001, Vol. 97, No. 2, pp. 459-464
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Circulating autoantibodies to oxidized cardiolipin correlate with
isoprostane F2 -VI levels and the extent of
atherosclerosis in ApoE-deficient mice: modulation by
vitamin E
Domenico Praticò,
Rajendra K. Tangirala,
Sohvi Hörkkö,
Joseph L. Witztum,
Wulf Palinski, and
Garret A. FitzGerald
From The Center for Experimental Therapeutics,
Department of Pharmacology, University of Pennsylvania,
Philadelphia, PA, and the Department of Medicine, University of
California, San Diego, La Jolla, CA.
Lipid peroxidation plays an important role in atherogenesis.
Previous studies suggested that autoantibodies against epitopes of oxidized low-density lipoprotein may indicate the extent or rate of
progression of atherosclerosis. The aim of this study was to
investigate whether autoantibodies to oxidized phospholipids, such as
oxidized cardiolipin (OxCL), correlate with levels of isoprostane
F2 -VI, a sensitive marker of in vivo lipid peroxidation, as well as with the extent of atherosclerosis. Two groups of
apolipoprotein E-deficient mice were fed chow with or without vitamin E
(2000 IU/kg diet) for 16 weeks. In untreated animals, autoantibodies against OxCL and urinary, plasma, and aortic isoprostane
F2-VI levels increased significantly. Vitamin E
treatment significantly reduced antibody titers, isoprostane levels,
and atherosclerosis at the end of the study, compared with untreated
mice. Autoantibodies to OxCL correlated with aortic isoprostane
F2-VI levels
(r2 = 0.42,
P = .001 for IgG and
r2 = 0.63, P < .001
for IgM). Both aortic isoprostane F2-VI levels
(r2 = 0.59, P < .001)
and titers of OxCL antibodies
(r2 = 0.70, P < .001
for IgG and r2 = 0.68,
P < .001 for IgM) correlated with the extent of aortic atherosclerosis. The fact that the levels of autoantibodies to OxCL
correlated with a sensitive direct measure of lipid peroxidation in
vivo and that both autoantibodies and aortic isoprostane
F2-VI levels correlated with the extent of
atherosclerosis suggests that antibodies to OxCL are a sensitive
indicator of in vivo lipid peroxidation and atherosclerosis.
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