One miR Level of Control

Abstract

See related article, pp 1407–1414 The ability of the endothelium to produce nitric oxide (NO) is important for the maintenance of vascular homeostasis, and either the altered expression of the endothelial NO synthase (eNOS) or its activity is thought to make a major contribution to the pathogenesis of vascular disease. The expression of eNOS is tightly regulated and numerous physiological and pathophysiological stimuli have been identified that modulate eNOS gene transcription, mRNA processing, and mRNA stability. A role for microRNAs (miRNAs) in the regulation of eNOS has long been suspected because knocking down Dicer, which is necessary for miRNA maturation, increased eNOS expression.1 In addition, miR-221 and miR-222 mimics partially reversed the increase in eNOS elicited by Dicer downregulation, although neither of these miRNAs directly targets the eNOS mRNA.1 In this issue of Hypertension , Sun et al2 report that miR-155 directly targets eNOS mRNA by binding to its 3′ untranslated region (UTR) to decrease enzyme expression and NO production. Which physiological situation could involve the regulation of eNOS expression via miR-155? There are several stimuli that have been reported to decrease eNOS levels and these are generally linked with inflammation, for example, proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin-1, interferon-γ, and bacterial lipopolysaccharide. Using these stimuli, Sun et al2 were able to demonstrate that proinflammatory cytokines increase miR-155 expression, most probably via AP-1 and nuclear factor-κB, and that …