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Pathogenic Autoimmunity in Atherosclerosis Evolves from HSP60-Reactive CD4 + T Cells

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Abstract  

Clinical evidence suggests anti-Hsp60 antibodies could contribute to atherosclerosis (AS) development, with unclear mechanisms. This study aims to explore the role of anti-HSP60-mediated autoimmunity in AS progression. HSP60-MHC tetramers were used to characterize HSP60-specific CD4 + T cells and assess TCR responses in mice. These cells were transplanted into AS mice to examine immune cell differentiation and infiltration in plaques and blood. Mice were injected with recombinant HSP60 or anti-HSP60 sera to evaluate effects on plaque progression and macrophage activity. Experiments with muMT–/–Apoe–/– mice examined humoral immunity's role in this autoimmunity. HSP60-reactive CD4 + T cells in AS mice differentiated into follicular helper cells, not Th1/Th17. Anti-HSP60 treatments increased macrophage infiltration and M1 polarization, indicating an anti-HSP60-driven inflammatory progression, dependent on humoral immunity. Anti-HSP60 influences macrophage infiltration, polarization, and plaque formation via humoral immunity, shedding light on its potential role in AS progression.

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Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

References

  1. Fan J, Watanabe T. Atherosclerosis: Known and unknown. Pathol Int. 2022;72(3):151–60.

    Article  PubMed  Google Scholar 

  2. Zhu Y, **an X, Wang Z, Bi Y, Chen Q, Han X, Tang D, Chen R. Research Progress on the Relationship between Atherosclerosis and Inflammation. Biomolecules. 2018;8(3):80.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Hansson GK, Hermansson A. The immune system in atherosclerosis. Nat Immunol. 2011;12(3):204–12.

    Article  CAS  PubMed  Google Scholar 

  4. Libby P. The changing landscape of atherosclerosis. Nature. 2021;592(7855):524–33.

    Article  CAS  PubMed  Google Scholar 

  5. Roh JS, Sohn DH. Damage-Associated Molecular Patterns in Inflammatory Diseases. Immune Netw. 2018;18(4):e27.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Mandal K, Jahangiri M, Xu Q. Autoimmune mechanisms of atherosclerosis. Handb Exp Pharmacol. 2005;170:723–43.

    Article  CAS  Google Scholar 

  7. Xu Q. Role of heat shock proteins in atherosclerosis. Arterioscler Thromb Vasc Biol. 2002;22(10):1547–59.

    Article  CAS  PubMed  Google Scholar 

  8. Xu Q, Metzler B, Jahangiri M, Mandal K. Molecular chaperones and heat shock proteins in atherosclerosis. Am J Physiol Heart Circ Physiol. 2012;302(3):H506–14.

    Article  CAS  PubMed  Google Scholar 

  9. Boteanu RM, Suica VI, Uyy E, Ivan L, Dima SO, Popescu I, Simionescu M, Antohe F. Alarmins in chronic noncommunicable diseases: Atherosclerosis, diabetes and cancer. J Proteomics. 2017;153:21–9.

    Article  CAS  PubMed  Google Scholar 

  10. Caruso Bavisotto C, Alberti G, Vitale AM, Paladino L, Campanella C, Rappa F, Gorska M, Conway de Macario E, Cappello F, Macario AJL, Marino Gammazza A. Hsp60 Post-translational Modifications: Functional and Pathological Consequences. Front Mol Biosci. 2020;7:95.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Cappello F, Mazzola M, Jurjus A, Zeenny MN, Jurjus R, Carini F, Leone A, Bonaventura G, Tomasello G, Bucchieri F, Conway de Macario E, Macario AJL. Hsp60 as a Novel Target in IBD Management: A Prospect. Front Pharmacol. 2019;10:26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Liyanagamage D, Martinus RD. Role of Mitochondrial Stress Protein HSP60 in Diabetes-Induced Neuroinflammation. Mediators Inflamm. 2020;2020:8073516.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Alard JE, Dueymes M, Youinou P, Jamin C. HSP60 and anti-HSP60 antibodies in vasculitis: they are two of a kind. Clin Rev Allergy Immunol. 2008;35(1–2):66–71.

    Article  CAS  PubMed  Google Scholar 

  14. Cappello F, Marino Gammazza A, Palumbo Piccionello A, Campanella C, Pace A, Conway de Macario E, Macario AJ. Hsp60 chaperonopathies and chaperonotherapy: targets and agents. Expert Opin Ther Targets. 2014;18(2):185–208.

    Article  CAS  PubMed  Google Scholar 

  15. Knoflach M, Bernhard D, Wick G. Anti-HSP60 immunity is already associated with atherosclerosis early in life. Ann N Y Acad Sci. 2005;1051:323–31.

    Article  CAS  PubMed  Google Scholar 

  16. Liao BH, Xu ZL, Gao F, Zhang SH, Liang RJ, Dong SH. The relationship between HSP60 gene polymorphisms and susceptibility to atherosclerosis. Eur Rev Med Pharmacol Sci. 2020;24(5):2667–73.

    PubMed  Google Scholar 

  17. Zonnar S, Saeedy SAG, Nemati F, Motamedi MJ, Raeespour H, Amani J. Decrescent role of recombinant HSP60 antibody against atherosclerosis in high-cholesterol diet immunized rabbits. Iran J Basic Med Sci. 2022;25(1):32–8.

    PubMed  PubMed Central  Google Scholar 

  18. Amirfakhryan H. Vaccination against atherosclerosis: An overview. Hellenic J Cardiol. 2020;61(2):78–91.

    Article  PubMed  Google Scholar 

  19. Moon JJ, Chu HH, Pepper M, McSorley SJ, Jameson SC, Kedl RM, Jenkins MK. Naive CD4(+) T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude. Immunity. 2007;27(2):203–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Cui X, Liu Y, Wang S, Zhao N, Qin J, Li Y, Fan C, Shan Z, Teng W. Circulating Exosomes Activate Dendritic Cells and Induce Unbalanced CD4+ T Cell Differentiation in Hashimoto Thyroiditis. J Clin Endocrinol Metab. 2019;104(10):4607–18.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiology, The Third Affiliated Hospital of Guangzhou Medical University, No. 63, Duobao Road, Liwan District, Guangzhou, 510150, China

    Shixiang Wang, Yongquan Chen, Danyan Zhou, Jiawei Zhang, Guofeng Guo & Youquan Chen

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  1. Shixiang Wang
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  2. Yongquan Chen
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  3. Danyan Zhou
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  4. Jiawei Zhang
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  5. Guofeng Guo
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  6. Youquan Chen
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Contributions

Shixiang Wang and Youquan Chen conceived and designed the study. Shixiang Wang and Yongquan Chen did the main experiments, Danyan Zhou, Jiawei Zhang and Guofeng Guo interpreted the data and drafted the article. Youquan Chen was responsible for reagents and materials and revised the article critically. All authors had final approval of the submitted versions.

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Correspondence to Youquan Chen.

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This work has been approved by the ethical committees at The Third Affiliated Hospital of Guangzhou Medical University.

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Communicated by Associate Editor Junjie **ao oversaw the review of this article.

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Wang, S., Chen, Y., Zhou, D. et al. Pathogenic Autoimmunity in Atherosclerosis Evolves from HSP60-Reactive CD4 + T Cells. J. of Cardiovasc. Trans. Res. (2024). https://doi.org/10.1007/s12265-024-10516-8

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  • DOI: https://doi.org/10.1007/s12265-024-10516-8

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