Reciprocal expression of MRTF-A and myocardin is crucial for pathological vascular remodelling in mice

EMBO J. 2012 Nov 28;31(23):4428-40. doi: 10.1038/emboj.2012.296. Epub 2012 Oct 26.


Myocardin-related transcription factor (MRTF)-A is a Rho signalling-responsive co-activator of serum response factor (SRF). Here, we show that induction of MRTF-A expression is key to pathological vascular remodelling. MRTF-A expression was significantly higher in the wire-injured femoral arteries of wild-type mice and in the atherosclerotic aortic tissues of ApoE(-/-) mice than in healthy control tissues, whereas myocardin expression was significantly lower. Both neointima formation in wire-injured femoral arteries in MRTF-A knockout (Mkl1(-/-)) mice and atherosclerotic lesions in Mkl1(-/-); ApoE(-/-) mice were significantly attenuated. Expression of vinculin, matrix metallopeptidase 9 (MMP-9) and integrin β1, three SRF targets and key regulators of cell migration, in injured arteries was significantly weaker in Mkl1(-/-) mice than in wild-type mice. In cultured vascular smooth muscle cells (VSMCs), knocking down MRTF-A reduced expression of these genes and significantly impaired cell migration. Underlying the increased MRTF-A expression in dedifferentiated VSMCs was the downregulation of microRNA-1. Moreover, the MRTF-A inhibitor CCG1423 significantly reduced neointima formation following wire injury in mice. MRTF-A could thus be a novel therapeutic target for the treatment of vascular diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis / pathology*
  • COS Cells
  • Cell Movement
  • Cells, Cultured
  • Chlorocebus aethiops
  • Femoral Artery / pathology
  • Immunohistochemistry / methods
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Muscle, Smooth, Vascular / metabolism*
  • NIH 3T3 Cells
  • Neointima / pathology
  • Nuclear Proteins / biosynthesis*
  • RNA Interference
  • Serum Response Factor / metabolism
  • Signal Transduction
  • Time Factors
  • Trans-Activators / biosynthesis*
  • Wound Healing


  • Mrtfa protein, mouse
  • Nuclear Proteins
  • Serum Response Factor
  • Trans-Activators
  • myocardin