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

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

doi:10.1016/j.atherosclerosis.2009.04.026

« Previous Next »Atherosclerosis
Volume 207, Issue 1 , Pages 74-83, November 2009

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

Rita Businaro
- Department of Cardiovascular Sciences, Sapienza University, Via A. Borelli 50, 00161 Rome, Italy
- Corresponding author. Tel.: +39 06 49918041; fax: +39 06 49918124.
Elisabetta Profumo
- Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy
Angela Tagliani
- Department of Cardiovascular Sciences, Sapienza University, Via A. Borelli 50, 00161 Rome, Italy
Brigitta Buttari
- Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy
Stefano Leone
- Department of Biology, University Roma TRE, Rome, Italy
Giulia D’Amati
- Department of Experimental Medicine, Sapienza University, Rome, Italy
Flora Ippoliti
- Department of Experimental Medicine, Sapienza University, Rome, Italy
Martina Leopizzi
- Department of Experimental Medicine, Sapienza University, Rome, Italy
Daniela D’Arcangelo
- Laboratory of Vascular Pathology, Istituto Dermopatico dell’Immacolata-IRCCS, Rome, Italy
Raffaele Capoano
- Department of Surgical Sciences, Sapienza University, Rome, Italy
Lorenzo Fumagalli
- Department of Cardiovascular Sciences, Sapienza University, Via A. Borelli 50, 00161 Rome, Italy
Bruno Salvati
- Department of Surgical Sciences, Sapienza University, Rome, Italy
Rachele Riganò
- Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy

Received 14 April 2008; received in revised form 20 April 2009; accepted 21 April 2009. published online 01 June 2009.

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.

Keywords: Heat-shock protein 90, Atherosclerosis, Carotid plaque, Antibodies, T lymphocytes