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(Circulation. 2005;112:1206-1213.)
© 2005 American Heart Association, Inc.

Vascular Medicine

Anti–Heat Shock Protein 60 Autoantibodies Induce Atherosclerosis in Apolipoprotein E–Deficient Mice via Endothelial Damage

Georgios Foteinos, BSc; Ali R. Afzal, MD, PhD; Kaushik Mandal, MD; Marjan Jahangiri, FRCS; Qingbo Xu, MD, PhD

From the Department of Cardiac and Vascular Sciences, St George’s University of London, London, UK.

Correspondence to Qingbo Xu, MD, PhD, Department of Cardiac and Vascular Sciences, St. George’s University of London, Cranmer Terrance, London SW17 0RE, UK. E-mail q.xu{at}sghms.ac.uk

Received March 5, 2005; revision received April 27, 2005; accepted May 25, 2005.

Background— Accumulating evidence established a positive association of anti–heat shock protein 60 (HSP60) autoantibodies and the presence of atherosclerosis in humans. However, whether these autoantibodies play a causal role in the development of atherosclerosis is unknown.

Methods and Results— In the present study, anti-HSP60 autoantibodies from blood of patients with coronary heart disease were isolated by affinity chromatography and injected into the tail vein of apolipoprotein E–deficient mice. Atherosclerotic lesions in aortas were significantly increased 8 weeks after injection. Furthermore, administration of a specific mouse monoclonal antibody (II-13) recognizing amino acid residues 288 to 366 of HSP60 effectively induced atherosclerotic lesions in apolipoprotein E–deficient mice. II-13 injection resulted in endothelial cell damage, followed by increased leukocyte attachment and accumulation of macrophages and smooth muscle cells in lesions. Interestingly, II-13–induced atherosclerosis was blocked by pretreatment of animals with F(ab)₂ segments derived from the antibody, but not mouse IgG F(ab)_2..

Conclusions— Autoantibodies recognizing amino acid residues 288 to 366 of HSP60 induce atherosclerosis via the mechanisms of autoimmune reactions to HSP60 expressed on arterial endothelial cells, which can be prevented by F(ab)₂ segments derived from these antibodies.

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