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-beta), 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.

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目的:为进一步阐明巨细胞病毒(CMV)促进动脉粥样硬化的机制,我们研究了在冠状动脉搭桥术(CABG)的CMV()和CMV(-)患者主动脉壁中细胞炎性信号和增殖信号的表达模式。
方法:采用PCR和原位杂交技术对68例CABG患者的主动脉活检和血样进行CMV-DNA检测。通过免疫组织化学研究了pp65抗原,粘附分子(ICAM-1,VCAM-1,E-选择素),生长因子(PDGF-AA,TGF-beta)和细胞增殖因子Ki-67的表达。 Logistic回归用于检验CMV的存在,血管炎症与动脉粥样硬化的传统非炎症危险因素之间的相关性。
结果:CMV-DNA在52名患者(76%)的主动脉组织中被检测到,并且主要定位在血管平滑肌细胞中。与CMV(-)患者相比,在CMV()患者中,主动脉内皮中粘附分子和生长因子的表达增加。发现CRP升高,粘附分子和生长因子的诱导与CMV()呈正相关。女性,吸烟和高脂血症被确定为CMV()的危险因素。
结论:平滑肌细胞中的CMV-DNA诱导了局部生长因子的表达以及内皮的激活,两者均可以促进动脉粥样硬化的发展。由于传统的动脉粥样硬化危险因素会增加主动脉CMV表现的可能性,因此我们建议CMV在介导动脉粥样硬化的进展中起关键作用。

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