Aspirin attenuates cytomegalovirus infectivity and gene expression mediated by cyclooxygenase-2 in coronary artery smooth muscle cells

被引:141
作者
Speir, E
Yu, ZX
Ferrans, VJ
Huang, ES
Epstein, SE
机构
[1] NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA
[2] Washington Hosp Ctr, Washington, DC 20010 USA
[3] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
关键词
antioxidant; atherosclerosis; cyclooxygenase; herpesvirus salicylate;
D O I
10.1161/01.RES.83.2.210
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Human cytomegalovirus (CMV) infection of smooth muscle cells generates reactive oxygen species (ROS) and thereby activates nuclear factor kappa B (NF kappa B), which causes expression of viral and cellular genes involved in immune and inflammatory responses. These changes could account for the mounting evidence suggesting that CMV may contribute causally to restenosis and atherosclerosis. We found that CMV induces ROS, at least partly, through a cyclooxygenase-2 (COX-2)-dependent pathway. Moreover, the viral immediate-early (IE) gene products, IE72 and IE84, have the capacity to transactivate the COX-2 promoter. Aspirin and indomethacin, both cyclooxygenase inhibitors as well as direct ROS scavengers, reduce CMV-induced ROS, probably through both of these activities. Sodium salicylate also has antiviral effects as the result of its potent antioxidant propel ties. Furthermore, by reducing ROS, aspirin and sodium salicylate inhibit CMV-induced NF kappa B activation, the ability of IE72 to transactivate its promoter, CMV IE gene expression after infection of SMCs, and CMV replication in SMCs. This is the first time aspirin has been shown to have antiviral effects. Thus, it is possible that aspirin has previously unrecognized therapeutic effects in various clinical situations, such as in viral infections (when used as an antipyretic agent) and in atherosclerosis (when used as an antiplatelet agent).
引用
收藏
页码:210 / 216
页数:7
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