Cytomegalovirus gene regulation by reactive oxygen species. Agents in atherosclerosis.
Oxidative stress is implicated in the pathogenesis of atherosclerosis, and of viral infections caused by sendai virus, influenza and HIV. Vascular oxidative stress is due to inflammatory and immune responses of vascular cells, and to reperfusion after recanalization of blocked arteries. Because human cytomegalovirus (CMV) may contribute to atherogenesis by several mechanisms, and coronary artery smooth muscle cells (SMC) are permissive for the virus, we examined CMV interactions with SMC. Infection causes generation of intracellular reactive oxygen species (ROS) which activate NF-kappa B, a cellular transcription factor. NF-kappa B mediates expression of the CMV promoter and of genes involved in the immune and inflammatory responses. Antioxidants or aspirin inhibit ROS, NF-kappa B and CMV.
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Cardiology Branch National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1650, USA. speire@nih.gov
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001483:Base Sequence; D003587:Cytomegalovirus / Q000235:genetics* / Q000302:isolation & purification; D017931:DNA Primers; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017874:Immediate-Early Proteins / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D017382:Reactive Oxygen Species; D014764:Viral Proteins; D019820:Xanthine / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D000975:Antioxidants; D017931:DNA Primers; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014764:Viral Proteins; D019820:Xanthine; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase