The current literature indicates an increasing body of evidence demonstrating that reactive oxygen species (ROS) 3 such as superoxide and hydrogen peroxide (H 2 O 2 ) are involved in the pathogenesis of many vascular diseases by modulating expression of a large number of genes related to vascular cell differentiation, proliferation, migration, and apoptosis (1-5). In this respect, increased ROS are associated with a variety of vascular disorders such as atherosclerosis, hypertension, restenosis after angioplasty or bypass, diabetic vascular complications, transplantation arteriopathy, and vascular aneurysm (5-12). ROS-mediated gene expression regulation has recently been extensively studied at epigenetic and transcriptional levels (3-5, 13, 14). It is clear that exposure of vascular cells to ROS modulates oxidation-sensitive signaling pathways and transcription factors that could be an important mechanism responsible for ROS-mediated expression changes of multiple genes.Recent studies reveal that post-transcriptional controls of gene expression such as translational regulation are as important as epigenetic and transcriptional controls (15, 16). However, the effects of ROS on gene expression regulation at the translational level are currently unclear.MicroRNAs (miRNAs) comprise a novel class of endogenous, small, noncoding RNAs that negatively regulate gene expression via degradation or translational inhibition of their target mRNAs (17)(18)(19)(20). Functionally, an individual miRNA is as important as a transcription factor, because it is able to regulate the expression of its multiple target genes. Analogous to the first RNA revolution in the 1980s when Cech (21) discovered the enzymatic activity of RNA, this recent discovery of miRNA and RNA interference may represent the second RNA revolution (22). Currently, ϳ700 miRNAs have been identified and sequenced in humans (23,24), and the estimated number of miRNA genes is as high as 1000 in the human genome (23-25). As a group, miRNAs may directly regulate at least 30% of the genes in a cell (25,26). It is not surprising that miRNAs are involved in the regulation of almost all major cellular functions, such as cell differentiation, proliferation/growth, mobility, and apoptosis. Therefore, miRNAs could be the pivotal regulators in normal development and physiology, as well as disease states, including vascular disease (24).Although miRNAs represent a new layer of gene expression regulators at the translational level, the effects of ROS on miRNA expression and the potential roles of miRNAs in ROS-* This work was supported, in whole or in part, by National Institutes of Health Grant HL080133. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C.