Heat-shock protein 90: A novel autoantigen in human carotid atherosclerosis

Rita Businaro, Elisabetta Profumo, Angela Tagliani, Brigitta Buttari, Stefano Leone, Giulia D'Amati, Flora Ippoliti, Martina Leopizzi, Daniela D'Arcangelo, Raffaele Capoano, Lorenzo Fumagalli, Bruno Salvati, Rachele Riganò

Research output: Contribution to journalArticle

Abstract

The known role of heat-shock proteins (HSPs) in the pathogenesis of atherosclerosis prompted us to investigate whether HSP90 is a target autoantigen of immune responses in patients with carotid atherosclerosis. Methods and results: The presence of HSP90 on 26 cryostat and 6 paraffin embedded sections of carotid atherosclerotic plaques was determined by immunohistochemistry and immunofluorescence. Plaque-infiltrating T lymphocytes from 9 patients and circulating PBMC from 26 patients and 21 healthy subjects were tested by cell proliferation assay and by flow cytometry and ELISA for cytokine production in response to HSP90. ELISA was used to detect soluble HSP90 and anti-HSP90 antibodies in serum samples. Strong HSP90 immunoreactivity was detected in the muscle and endothelial cell layer and in the inflammatory infiltrate of carotid plaques. Plaque-derived and circulating T lymphocytes from patients proliferated in response to HSP90 whereas cells from healthy subjects did not. HSP90-specific T lymphocytes expressed IFN-γ and IL-4 suggesting concomitant Th1 and Th2 activation. ELISA detected soluble HSP90 in 42% and anti-HSP90 antibodies in 46% of patients' sera. Conclusions: These new findings, showing that HSP90 is overexpressed in plaque and serum from patients with atherosclerosis and induces an immune response in these patients, implicate HSP90 as a possible target autoantigen in the pathogenesis of carotid atherosclerosis.

Original languageEnglish
Pages (from-to)74-83
Number of pages10
JournalAtherosclerosis
Volume207
Issue number1
DOIs
Publication statusPublished - Nov 2009

Keywords

  • Antibodies
  • Atherosclerosis
  • Carotid plaque
  • Heat-shock protein 90
  • T lymphocytes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Businaro, R., Profumo, E., Tagliani, A., Buttari, B., Leone, S., D'Amati, G., Ippoliti, F., Leopizzi, M., D'Arcangelo, D., Capoano, R., Fumagalli, L., Salvati, B., & Riganò, R. (2009). Heat-shock protein 90: A novel autoantigen in human carotid atherosclerosis. Atherosclerosis, 207(1), 74-83. https://doi.org/10.1016/j.atherosclerosis.2009.04.026