title: Related transcriptional enhancer factor 1 increases endothelial-dependent microvascular relaxation and proliferation.
abstract: OBJECTIVE
  Related transcriptional enhancer factor 1 (RTEF-1) is a key transcriptional regulator in endothelial function. In this study, we investigated a possible role for RTEF-1 in the regulation of microvascular relaxation and the underlying mechanism involved. Activation of fibroblast growth factor receptor 1 (FGFR1) by FGFs increases vasodilation, although transcriptional control of the molecular mechanisms underlying FGFR1 is still unclear.
  
  
  METHODS
  We demonstrated that RTEF-1 stimulated FGFR1 expression at the transcriptional level, specifically an area including Sp1 elements, as evidenced by promoter assays. Additionally, RTEF-1 increased FGFR1 mRNA and protein expression in vitro and in VE-cadherin-promoted RTEF-1 (VE-Cad/RTEF-1) transgenic mice, whereas RTEF-1 siRNA blocked the upregulation of FGFR1 expression. Furthermore, increased endothelial-dependent microvessel relaxation was observed in the coronary arteries of VE-Cad/RTEF-1 mice, and increased proliferation was observed in RTEF-1-overexpressing cells, both of which correlated to increased FGF/FGFR1 signaling and endothelial nitric oxide synthase (eNOS) upregulation. Our results indicate that RTEF-1 acts as a transcriptional stimulator of FGFR1 and is involved in FGF pathways by increasing microvessel dilatation via eNOS.
  
  
  CONCLUSIONS
  These findings suggest that RTEF-1 plays an important role in FGFR1- stimulated vasodilatation. Understanding the effect of RTEF-1 in microvessel relaxation may provide beneficial knowledge in improving treatments in regards to ischemic vascular disorders.
authors.affiliation: Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Angela F
authors.initials: AF
authors.lastname: Messmer-Blust
authors.forename: Cuili
authors.initials: C
authors.lastname: Zhang
authors.forename: Jue-Lon
authors.initials: JL
authors.lastname: Shie
authors.forename: Qinhui
authors.initials: Q
authors.lastname: Song
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.forename: Isabel
authors.initials: I
authors.lastname: Lubenec
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Liu
authors.forename: Frank
authors.initials: F
authors.lastname: Sellke
authors.forename: Jian
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D002417:Cattle; D049109:Cell Proliferation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D055806:Microvessels / Q000502:physiology*; D009124:Muscle Proteins / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000502:physiology; D011401:Promoter Regions, Genetic; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000032:analysis / Q000235:genetics; D015398:Signal Transduction; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000502:physiology*; D014664:Vasodilation
chemical_list: D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D000091262:TEA Domain Transcription Factors; C486309:TEAD4 protein, human; D014157:Transcription Factors; D052250:Nitric Oxide Synthase Type III; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1