A relationship between serological markers of chronic C. pneumoniae and CMV infection and hsp60 in patients with atherosclerotic carotid stenosis

Abstract

A number of epidemiological studies conducted over the last decade indicate a relationship between specific pathogen infections and the development of atherosclerosis, although no pathogenetic pathways connecting these two have been determined. Recent reports support the role of heat shock proteins (HSPs) in atherogenesis. The HSPs are also believed to be a link between the infection and the development of atherosclerotic lesions. The aims of study: Immunohistochemical evaluation of carotid artery segments to show the relationship between the presence of heat shock proteins and the serum levels of anti-hsp60 antibodies. An attempt to demonstrate a relationship between an expression of chronic C. pneumoniae and CMV antigens. Material and Methods: The study included 41 patients qualified for carotid artery endarterectomy and 18 healthy volunteers of corresponding age. Levels of anti-hsp60, anti-C. pneumoniae IgA and IgG, anti-CMV IgG antibodies as well as hsCRP were determined. Results: The mean serum levels of anti-hsp60 antibodies were higher in patients with advanced atherosclerosis as compared to healthy volunteers (55.3±64.1 vs 32.8±29.8; p < 0.05). There was a strong correlation between anti-hsp60 antibodies and the expression of hsp60 in carotid arterial wall, as confirmed by immunohistochemical evaluation. The study group showed statistically significant higher levels of hsCRP. Furthermore, statistically significant higher serum levels of anti-C. pneumoniae IgG and IgA as well as anti-CMV IgG antibodies were found in the study group as compared to controls. No correlation was shown between the markers of chronic infection induced by the tested pathogens and serum levels of anti-HSP and hsCRP. Conclusions: Higher protein expression in vascular walls is closely correlated with the level of anti-hsp60. At the same time, no significant relationship between anti-hsp60 antibodies and serological markers of infection was observed, which may only indicate an indirect role of infection in the assessment of breaking the immunological tolerance against autologous HSPs.

Atherosclerosis. Macrophages. Viral infections

“…The hypothesis, put forward by A. Assinger, suggests a possible effect of the virus on the platelets. CMV is able to transmit activating signals that stimulate the migration of the leukocytes through the activation of TLR-2 platelet receptors [53].…”

Heat shock protein 60 and cardiovascular diseases: An intricate love‐hate story

“…87 Evidence has demonstrated that bacterial and human HSP60 participate in the pathophysiology of atherosclerosis at different points of the disease progression elucidating its importance as a marker of disease and as a potential target for treatment. 9,10,[95][96][97] A study reported by Xu et al 95 might be one of the first papers where efforts were made to establish the role of HSPs in atherogenesis. Normocholesterolemic rabbits were immunized with HSP65, a major antigenic component of M. tuberculosis (mHSP65).…”

“…However, if a sudden rupture of the plaque occurs, coronary artery occlusion can occur, causing a myocardial infarction 87 . Evidence has demonstrated that bacterial and human HSP60 participate in the pathophysiology of atherosclerosis at different points of the disease progression elucidating its importance as a marker of disease and as a potential target for treatment 9,10,95–97 …”

“…T cell activation requires recognition of HSP60 epitopes, for which presentation of immunogenic peptides via MHC molecules is necessary. Analysis of carotid endarterectomy samples from patients with carotid artery stenosis identified on the surface of macrophages the presence of HSP60 on both vasa vasorum and carotid artery endothelial cells using immunohistochemistry 97 . Serum titers for antibodies for HSP60, C. pneumoniae and cytomegalovirus were increased, although no markers related to infection to these last two pathogens were found 97 .…”

“…Analysis of carotid endarterectomy samples from patients with carotid artery stenosis identified on the surface of macrophages the presence of HSP60 on both vasa vasorum and carotid artery endothelial cells using immunohistochemistry 97 . Serum titers for antibodies for HSP60, C. pneumoniae and cytomegalovirus were increased, although no markers related to infection to these last two pathogens were found 97 . These findings support the idea that infection may be one of the initiating factors for atherosclerosis, where high sequence homology and epitope sharing between self‐HSP60 and its microbial counterparts may promote antibody secretion with subsequent deposition of immune complexes and endothelial dysfunction.…”