Cytomegalovirus and Proliferative Signals in the Vascular Wall of CABG Patients

Abstract

Objective: To further elucidate the mechanism by which cytomegalovirus (CMV) may promote atherosclerosis, we studied the expression pattern of cellular inflammatory and proliferative signals in the aortic wall of CMV⁽⁺⁾ and CMV^(-) patients undergoing coronary artery bypass grafting (CABG). Methods: Aortic biopsies and blood samples of 68 CABG patients were investigated for CMV‐DNA by PCR and in situ hybridisation. Expression of pp65 antigen, adhesion molecules (ICAM-1, VCAM-1, E-selectin), growth factors (PDGF‐AA, TGF-β), and the cellular proliferation factor Ki-67 was studied by immunohistochemistry. Logistic regression was used to test the correlation between the presence of CMV, vascular inflammation, and traditional noninflammatory risk factors for atherosclerosis. Results: CMV‐DNA was detected in the aortic tissue of 52 (76 %) patients, and was localised predominantly in vascular smooth muscle cells. In CMV⁽⁺⁾ patients, the expression of adhesion molecules and growth factors in the aortic endothelium was increased compared with CMV^(-) patients. A positive correlation of elevated CRP, the induction of adhesion molecules and growth factors and CMV⁽⁺⁾ was found. Female gender, smoking, and hyperlipidaemia were identified as risk factors for CMV⁽⁺⁾. Conclusions: CMV‐DNA in smooth muscle cells induces local growth factor expression as well as endothelial activation, both of which can promote the progression of atherosclerosis. Since traditional atherogenic risk factors increase the likelihood of aortic CMV manifestation, we suggest that CMV plays a crucial role in mediating the progression of atherosclerosis.

Key words

Atherosclerosis - cytomegalovirus - adhesion molecules - growth factors

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