The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: Correlates with human disease

L. Elia, M. Quintavalle, J. Zhang, R. Contu, L. Cossu, M. V G Latronico, K. L. Peterson, C. Indolfi, D. Catalucci, J. Chen, Sara Courtneidge, G. Condorelli

385 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1590-1598
Number of pages9
JournalCell Death and Differentiation
Volume16
Issue number12
DOIs
StatePublished - 2009
Externally publishedYes

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ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Elia, L., Quintavalle, M., Zhang, J., Contu, R., Cossu, L., Latronico, M. V. G., Peterson, K. L., Indolfi, C., Catalucci, D., Chen, J., Courtneidge, S., & Condorelli, G. (2009). The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: Correlates with human disease. Cell Death and Differentiation, 16(12), 1590-1598. https://doi.org/10.1038/cdd.2009.153