© 1999 American Heart Association, Inc.
Original Contributions |
Enhanced Fatty Streak Formation in C57BL/6J Mice by Immunization With Heat Shock Protein-65
From the Research Unit of Autoimmune Diseases, Department of Medicine B (J.G., Y.S., B.G., P.K.), the Institute of Pathology (A.A., J.K.), and the Institute of Lipid and Atherosclerosis Research (P.K., A.S., D.H.), Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and the Institute of Biomedical Aging Research, Austrian Academy of Sciences, and Institute for General and Experimental Pathology, University of Innsbruck Medical School, Innsbruck, Austria (G.W.).
Correspondence and reprint requests to Prof Yehuda Shoenfeld, Department of Medicine `B,' Sheba Medical Center, Tel-Hashomer 52621, Israel. E-mail shoenfel{at}post.tau.ac.il
Abstract—Recent data suggest that the immune system is involved in atherogenesis. Thus, interest has been raised as to the possible antigens that could serve as the initiators of the immune reaction. In the current work, we studied the effects of immunization with recombinant heat shock protein-65 (HSP-65) and HSP-65–rich Mycobacterium tuberculosis (MT) on early atherogenesis in C57BL/6J mice fed either a normal chow diet or a high-cholesterol diet (HCD). A rapid, cellular immune response to HSP-65 was evident in mice immunized with HSP-65 or with MT but not in the animals immunized with phosphate-buffered saline (PBS) alone. Early atherosclerosis was significantly enhanced in HCD-fed mice immunized with HSP-65 (n=10; mean aortic lesion size, 45 417±9258 µm2) or MT (n=15; 66 350±6850 µm2) compared with PBS-injected (n=10; 10 028±3599 µm2) or nonimmunized (n=10; 9500±2120 µm2) mice. No fatty streak lesions were observed in mice fed a chow diet regardless of the immunization protocol applied. Immunohistochemical analysis of atherosclerotic lesions from the HSP-65– and MT-immunized mice revealed infiltration of CD4 lymphocytes compared with the relatively lymphocyte-poor lesions in the PBS-treated or nonimmunized mice. Direct immunofluorescence analysis of lesions from HSP-65– and MT-immunized mice fed an HCD exhibited extensive deposits of immunoglobulins compared with the fatty streaks in the other study groups, consistent with the larger and more advanced lesions found in the former 2 groups. This model, which supports the involvement of HSP-65 in atherogenesis, furnishes a valuable tool to study the role of the immune system in atherogenesis.
Key Words: atherosclerosis • autoantibodies • heat shock protein-65 • oxidized LDL • Mycobacterium tuberculosis
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