Cardiovascular Research Advance Access [Accepted Manuscript] published online on June 11, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn156
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Role of microRNAs in vascular diseases, inflammation and angiogenesis
Molecular Cardiology, Internal Medicine III, University of Frankfurt, Germany
Address for correspondence: Stefanie Dimmeler, PhD Department of Molecular Cardiology Internal Medicine III University of Frankfurt Theodor-Stern-Kai 7 60590 Frankfurt Germany Fax: +49-69-6301-7113, Phone: +49-69-6301-7440 e-mail: dimmeler{at}em.uni-frankfurt.de
The integrity of the endothelial monolayer is fundamental for the homeostasis of the vascular system. Functional endothelial cells are also required for the growth of new blood vessels during neovascularization. Although multiple growth factors have been shown to regulate angiogenesis and vascular development, little is known about the complex upstream regulation of gene expression and translation. MicroRNAs (miRNAs) are an emerging class of highly conserved, non-coding small RNAs that regulate gene expression on the post-transcriptional level by inhibiting the translation of protein from mRNA or by promoting the degradation of mRNA. More than 500 human miRNAs have been identified so far, and increasing evidence indicates that miRNAs have distinct expression profiles and play crucial roles in various physiological and pathological processes such as cardiogenesis, hematopoietic lineage differentiation, and oncogenesis. Meanwhile, a few specific miRNAs that regulate endothelial cell functions and angiogenesis have been described. Let7-f, miR-27b and mir-130a were identified as pro-angiogenic miRNAs. In contrast, miR-221 and miR-222 inhibit endothelial cell migration, proliferation, and angiogenesis in vitro by targeting the stem cell factor receptor c-kit and indirectly regulating endothelial nitric oxide synthase expression. Moreover, some miRNAs are involved in tumor angiogenesis such as the miR-17-92 cluster and miR-378. Early studies also indicate the contribution of specific miRNAs (e.g. miR-155, miR-21 and miR-126) to vascular inflammation and diseases. Thus, the identification of miRNAs and their respective targets may offer new therapeutic strategies to treat vascular diseases such as atherosclerosis, to improve neovascularization after ischemia, or to prevent tumor progression.
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