Journal
CELL DEATH AND DIFFERENTIATION
Volume 16, Issue 12, Pages 1590-1598Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2009.153
Keywords
microRNA; vascular smooth muscle cells; cell migration
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Funding
- EUGeneHeart [LSHM-CT-2005-018833]
- Italian Ministry of Education
- Fondation LeDucq
- National Cancer Institute
- Mathers Foundation
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Mechanisms controlling vascular smooth muscle cell (VSMC) plasticity and renewal still remain to be elucidated completely. A class of small RNAs called microRNAs (miRs) regulate gene expression at the post-transcriptional level. Here, we show a critical role of the miR-143/145 cluster in SMC differentiation and vascular pathogenesis, also through the generation of a mouse model of miR-143 and -145 knockout (KO). We determined that the expression of miR-143 and -145 is decreased in acute and chronic vascular stress (transverse aortic constriction and in aortas of the ApoE KO mouse). In human aortic aneurysms, the expression of miR-143 and -145 was significantly decreased compared with control aortas. In addition, overexpression of miR-143 and -145 decreased neointimal formation in a rat model of acute vascular injury. An in-depth analysis of the miR-143/145 KO mouse model showed that this miR cluster is expressed mostly in the SMC compartment, both during development and postnatally, in vessels and SMC-containing organs. Loss of miR-143 and miR-145 expression induces structural modifications of the aorta, because of an incomplete differentiation of VSMCs. In conclusion, our results show that the miR-143/145 gene cluster has a critical role during SMC differentiation and strongly suggest its involvement in the reversion of the VSMC differentiation phenotype that occurs during vascular disease. Cell Death and Differentiation (2009) 16, 1590-1598; doi: 10.1038/cdd.2009.153; published online 9 October 2009
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