Interaction of antibodies against cytomegalovirus with heat-shock protein 60 in pathogenesis of atherosclerosis
| Autor: | Antonio Puccetti, Roberto Corrocher, Enrico Millo, Ruggero Beri, Riccardo Navone, Alberto Margonato, Nicola Martinelli, Claudio Lunardi, Caterina Bason, Domenico Girelli, Patrizia Puccetti, Oliviero Olivieri |
|---|---|
| Přispěvatelé: | Bason, C, Corrocher, R, Lunardi, C, Puccetti, P, Olivieri, O, Girelli, D, Navone, R, Beri, R, Millo, E, Margonato, Alberto, Martinelli, N, Puccetti, A. |
| Rok vydání: | 2003 |
| Předmět: |
Male
Congenital cytomegalovirus infection Sequence Homology Apoptosis Coronary Artery Disease Cross Reactions Biology Antibodies Viral medicine.disease_cause Epitope HSP60 atherosclerosis cytomegalovirus Autoimmunity Pathogenesis Western blot Antibody Specificity Sequence Analysis Protein Heat shock protein medicine Humans medicine.diagnostic_test Endothelial Cells Chaperonin 60 General Medicine Middle Aged medicine.disease Virology Cytomegalovirus Infections Immunology biology.protein Female Antibody |
| Popis: | Background 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 pathogenosis of atherosclerosis. RI Olivieri, Oliviero/A-9126-2008; Girelli, Domenico/B-1183-2008 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|