Infections and autoimmunity have been implicated in the pathogenesis of atherosclerosis. Cytomegalovirus has been shown to contribute to the disease. Autoantibodies against human heat-shock protein (HSP) 60 are present in most atherosclerotic patients, and their titre correlates with disease severity, suggesting that anti-HSP60 might be implicated in disease pathogenesis. We postulated that cytomegalovirus infection might induce antibodies able to bind human HSP60 and to cause endothelial-cell damage. METHODS: We studied 180 patients with coronary-artery disease, raised high sensitivity C-reactive protein concentrations, and presence or absence of traditional risk factors; 90 patients with coronary-artery disease, normal values for high sensitivity C-reactive protein, and no traditional risk factors; and 98 controls. Individual sera were used to define the relevant epitope of HSP60 by ELISA. Affinity purified IgGs were used to identify endothelial cell-surface ligands by western blot and to induce apoptotic cell death. FINDINGS: We identified an 11 aminoacid sequence of HSP60 that was recognised by most patients with coronary-artery disease. This peptide shares homology with cytomegalovirus-derived proteins UL122 and US28. The same patients' sera recognised UL122-derived and US28-derived peptides. Purified IgGs against HSP60 and the viral peptides bound non-stressed human endothelial cells and induced endothelial-cell apoptosis by interaction with cell-surface molecules. INTERPRETATION: During cytomegalovirus infection, antibodies against the virus can arise that are able to crossreact with human HSP60 and cause apoptosis of non-stressed endothelial cells, which is judged a primary event in the pathogenesis of atherosclerosis.

Interaction of antibodies against cytomegalovirus with heat-shock protein 60 in pathogenesis of atherosclerosis.

BASON, Caterina;CORROCHER, Roberto;LUNARDI, Claudio;OLIVIERI, Oliviero;GIRELLI, Domenico;BERI, Ruggero;MARTINELLI, Nicola;
2003

Abstract

Infections and autoimmunity have been implicated in the pathogenesis of atherosclerosis. Cytomegalovirus has been shown to contribute to the disease. Autoantibodies against human heat-shock protein (HSP) 60 are present in most atherosclerotic patients, and their titre correlates with disease severity, suggesting that anti-HSP60 might be implicated in disease pathogenesis. We postulated that cytomegalovirus infection might induce antibodies able to bind human HSP60 and to cause endothelial-cell damage. METHODS: We studied 180 patients with coronary-artery disease, raised high sensitivity C-reactive protein concentrations, and presence or absence of traditional risk factors; 90 patients with coronary-artery disease, normal values for high sensitivity C-reactive protein, and no traditional risk factors; and 98 controls. Individual sera were used to define the relevant epitope of HSP60 by ELISA. Affinity purified IgGs were used to identify endothelial cell-surface ligands by western blot and to induce apoptotic cell death. FINDINGS: We identified an 11 aminoacid sequence of HSP60 that was recognised by most patients with coronary-artery disease. This peptide shares homology with cytomegalovirus-derived proteins UL122 and US28. The same patients' sera recognised UL122-derived and US28-derived peptides. Purified IgGs against HSP60 and the viral peptides bound non-stressed human endothelial cells and induced endothelial-cell apoptosis by interaction with cell-surface molecules. INTERPRETATION: During cytomegalovirus infection, antibodies against the virus can arise that are able to crossreact with human HSP60 and cause apoptosis of non-stressed endothelial cells, which is judged a primary event in the pathogenesis of atherosclerosis.
HSP60; atherosclerosis; cytomegalovirus
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11562/16094
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