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A novel atherogenic epitope from Mycobacterium tuberculosis heat shock protein 65 enhances atherosclerosis in rabbit and LDL receptor-deficient mice

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Abstract

Previous studies have established that Mycobacterium tuberculosis heat shock protein 65 (mHSP65) plays an important role in immune-associated diseases as an autoimmune factor. Some overlapping epitopes of mHSP65 may serve as initiators of both atherosclerosis and other autoimmune-associated diseases. In the present study, atherosclerosis was significantly enhanced in high-cholesterol diet (HCD)-fed New Zealand white rabbits immunized with mHSP6591–105 compared with PBS-immunized or BSA-immunized rabbits. Immunizing wild-type C57BL/6J mice with mHSP6591–105 induced the aortic endothelial injury. Although western blot demonstrated that specific antibodies against mHSP6591–105 can cross-react with recombinant human heat shock protein 60, specific antibodies against mHSP6591–105 had no direct effects on HUVECs in vitro. Laser scanning confocal microscopy showed that mHSP6591–105 localized in the cytoplasm of HUVECs, even when HUVECs were heat shocked at 42°C. mHSP6591–105-specific splenic cells secreted more IFN-γ than controls. Also, adoptive transfer of mHSP6591–105-specific splenic cells can accelerate atherosclerosis in ldlr −/− mice. We can conclude that the (auto)immune response to mHSP6591–105 accelerates atherosclerosis in animal models, and that the response of Th1 plays an important role in this progress.

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Acknowledgments

This work was supported in part by the China National Natural Science Fund Committee (grant nos. 30500458, 30701023, 30672464, 30872393 and 30772570); the Natural Science Foundation of Jiangsu Province (no. BK 2007170).

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Authors and Affiliations

  1. Minigene Pharmacy Laboratory, School of Life Science and Technology, China Pharmaceutical University, Tongjia Xiang 24, 210009, Nanjing, People’s Republic of China

    Qiyan Xiong, Xiangbing Hu, Yunxiao Sun, Huiyong Zhang, Yong Lu & Jingjing Liu

  2. Department of Pharmacology, School of Pharmacy, Nanjing Medical University, 210029, Nanjing, China

    Yu Zhang

  3. Jiangsu Province Hospital of TCM, 210029, Nanjing, China

    Xiying Tan

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  1. Yu Zhang
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  2. Qiyan Xiong
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Correspondence to Jingjing Liu.

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Zhang, Y., Xiong, Q., Hu, X. et al. A novel atherogenic epitope from Mycobacterium tuberculosis heat shock protein 65 enhances atherosclerosis in rabbit and LDL receptor-deficient mice. Heart Vessels 27, 411–418 (2012). https://doi.org/10.1007/s00380-011-0183-8

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  • DOI: https://doi.org/10.1007/s00380-011-0183-8

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