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

Research output: Contribution to journalArticle

383 Citations (Scopus)

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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Smooth Muscle Myocytes
Blood Vessels
Aorta
Homeostasis
Maintenance
Vascular Smooth Muscle
Knockout Mice
Aortic Aneurysm
Vascular System Injuries
Apolipoproteins E
Multigene Family
MicroRNAs
Vascular Diseases
Constriction
Cell Differentiation
RNA
Phenotype
Gene Expression
Cell Plasticity

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice : Correlates with human disease. / Elia, L.; Quintavalle, M.; Zhang, J.; Contu, R.; Cossu, L.; Latronico, M. V G; Peterson, K. L.; Indolfi, C.; Catalucci, D.; Chen, J.; Courtneidge, Sara; Condorelli, G.

In: Cell Death and Differentiation, Vol. 16, No. 12, 2009, p. 1590-1598.

Research output: Contribution to journalArticle

Elia, L, Quintavalle, M, Zhang, J, Contu, R, Cossu, L, Latronico, MVG, Peterson, KL, 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, vol. 16, no. 12, pp. 1590-1598. https://doi.org/10.1038/cdd.2009.153
Elia, L. ; Quintavalle, M. ; Zhang, J. ; Contu, R. ; Cossu, L. ; Latronico, M. V G ; Peterson, K. L. ; Indolfi, C. ; Catalucci, D. ; Chen, J. ; Courtneidge, Sara ; Condorelli, G. / The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice : Correlates with human disease. In: Cell Death and Differentiation. 2009 ; Vol. 16, No. 12. pp. 1590-1598.
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