Role of microRNAs in vascular diseases, inflammation, and angiogenesis.
The integrity of the endothelial monolayer is fundamental for the homoeostasis 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, haematopoietic 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 tumour 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 ischaemia, or to prevent tumour progression.
Department of Molecular Cardiology, Internal Medicine III, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Carmen
C
Urbich
Angelika
A
Kuehbacher
Stefanie
S
Dimmeler
D000818:Animals; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism*; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D035683:MicroRNAs / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional; D043244:Ribonuclease III / Q000378:metabolism; D014652:Vascular Diseases / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy
D035683:MicroRNAs; C517918:DROSHA protein, human; C513400:Drosha protein, mouse; D043244:Ribonuclease III