Angiogenic factor with G patch and FHA domains 1 is a novel regulator of vascular injury

Bisheng Zhou, Sheng Zeng, Nan Li, Liming Yu, Guang Yang, Yuyu Yang, Xinjian Zhang, Mingming Fang, Jun Xia, Yong Xu

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Objective - Phenotypic modulation of vascular smooth muscle cells represents a hallmark event in vascular injury. The underlying mechanism is not completely sorted out. We investigated the involvement of angiogenic factor with G patch and FHA domains 1 (Aggf1) in vascular injury focusing on the transcriptional regulation of vascular smooth muscle cell signature genes. Approach and Results - We report here that Aggf1 expression was downregulated in several different cell models of phenotypic modulation in vitro and in the vessels after carotid artery ligation in mice. Adenovirus-mediated Aggf1 overexpression dampened vascular injury and normalized vascular smooth muscle cell signature gene expression. Mechanistically, Aggf1 interacted with myocardin and was imperative for the formation of a serum response factor-myocardin complex on gene promoters. In response to injurious stimuli, kruppel-like factor 4 was recruited to the Aggf1 promoter and enlisted histone deacetylase 11 to repress Aggf1 transcription. In accordance, depletion of kruppel-like factor 4 or histone deacetylase 11 restored Aggf1 expression and abrogated vascular smooth muscle cell phenotypic modulation. Finally, treatment of a histone deacetylase 11 inhibitor attenuated vascular injury in mice. Conclusions - Therefore, we have unveiled a previously unrecognized role for Aggf1 in regulating vascular injury.

Original languageEnglish (US)
Pages (from-to)675-684
Number of pages10
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number4
StatePublished - 2017
Externally publishedYes


  • Carotid arteries
  • Epigenetics
  • Histone deacetylases
  • Muscle
  • Serum response factor
  • Smooth
  • Vascular

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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