Lebedeva A M, Shpektor A V, Vasilieva E Yu, Margolis L B
Department of Cardiology and Laboratory of Atherothrombosis, A. I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of the Russian Federation, Moscow, 127473, Russia.
Section on Intercellular Interactions, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Biochemistry (Mosc). 2018 Dec;83(12):1437-1447. doi: 10.1134/S0006297918120027.
Atherosclerosis underlies the development of many cardiovascular diseases that continue to hold a leading place among the causes of death in developed countries. The role of activated immune cells in atherosclerosis progression has been convincingly demonstrated, but the mechanism of their action remains poorly investigated. Since atherosclerosis is associated with chronic inflammatory response, involvement of viral and bacterial infections in atherogenesis has been examined. A special place among the infectious agents is held by human herpesviruses as the most common persistent viruses in human population coupled to chronic inflammation during atherosclerosis. We found that activation of cytomegalovirus (CMV, human herpesvirus 5) infection is associated with the emergence of acute coronary syndrome, which is in a good agreement with the data on productive CMV infection published elsewhere. In this review, we discuss the data obtained by us and other researchers regarding the role of cytomegalovirus infection and related potential mechanisms resulting in the expansion of atherosclerotic plaques during ischemic heart disease and stroke, including virus transfer to immune and endothelial cells via extracellular vesicles. In particular, the data presented in the review demonstrate that virus spreading in the vascular wall triggers immune system activation in atherosclerotic plaques and causes endothelial dysfunction. Moreover, productive CMV infection in patients with acute myocardial infarction correlates with the extent of endothelial dysfunction. The mechanisms described by us and other researchers may explain the role of CMV infection in atherosclerosis and development of ischemic heart disease.
动脉粥样硬化是许多心血管疾病发展的基础，这些疾病在发达国家的死因中仍占据主导地位。活化免疫细胞在动脉粥样硬化进展中的作用已得到令人信服的证明，但其作用机制仍研究不足。由于动脉粥样硬化与慢性炎症反应相关，因此已对病毒和细菌感染在动脉粥样硬化发生中的作用进行了研究。在感染因子中，人类疱疹病毒占据特殊地位，因为它们是人类最常见的持续性病毒，且与动脉粥样硬化期间的慢性炎症相关。我们发现巨细胞病毒（CMV，人类疱疹病毒5型）感染的激活与急性冠状动脉综合征的出现有关，这与其他地方发表的关于CMV感染活跃的数据一致。在这篇综述中，我们讨论了我们和其他研究人员获得的关于巨细胞病毒感染的作用以及导致缺血性心脏病和中风期间动脉粥样硬化斑块扩大的相关潜在机制的数据，包括病毒通过细胞外囊泡转移至免疫细胞和内皮细胞。特别是，综述中呈现的数据表明，病毒在血管壁中的传播会触发动脉粥样硬化斑块中的免疫系统激活并导致内皮功能障碍。此外，急性心肌梗死患者中活跃的CMV感染与内皮功能障碍的程度相关。我们和其他研究人员描述的机制可能解释了CMV感染在动脉粥样硬化和缺血性心脏病发展中的作用。
