title: The endothelium-dependent effect of RTEF-1 in pressure overload cardiac hypertrophy: role of VEGF-B.
abstract: OBJECTIVE
  Related transcription enhancer factor-1 (RTEF-1) has previously been demonstrated to play an important role in both endothelial cells and cardiomyocytes. However, the function of RTEF-1 in the communication between these two adjacent cell types has not been elucidated.
  
  
  RESULTS
  We have found that endothelium-specific RTEF-1 transgenic mice (VE-Cad/RTEF-1) developed significant cardiac hypertrophy after transverse aortic constriction surgery, as evidenced by an increased ratio of heart weight to tibia length, enlarged cardiomyocyte size, thickened left ventricular wall and elevated expression of hypertrophic gene markers, with up-regulation of vascular endothelial growth factor B (VEGF-B). Additionally, VEGF-B was increased in endothelial cells from VE-Cad/RTEF-1 mice, as well as in endothelial cells with forced RTEF-1 expression (HMEC-1/RTEF-1), and coincidentally decreased when RTEF-1 was deficient in HMEC-1. Using chromatin immunoprecipitation and luciferase assays, we found that RTEF-1 increased VEGF-B promoter activity through a direct interaction. Hypertrophy-associated genes and protein synthesis were up-regulated in cardiomyocytes that were incubated with conditioned medium from HMEC-1/RTEF-1 and the endothelial cells of VE-Cad/RTEF-1 mice. This effect could be abrogated by treating the myocytes with VEGF-B small interfering RNA and extracellular signal-regulated kinase 1/2 inhibitor.
  
  
  CONCLUSIONS
  Our data demonstrated that increased RTEF-1 in endothelial cells upregulates VEGF-B, which is able to stimulate hypertrophic genes in cardiomyocytes. These results suggest that the RTEF-1-driven increase of VEGF-B plays an important role in communication between the endothelium and myocardium.
authors.affiliation: Department of Physiology, Fourth Military Medical University, Xi'an, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.forename: Qinhui
authors.initials: Q
authors.lastname: Song
authors.forename: Jiaping
authors.initials: J
authors.lastname: Wu
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Philbrick
authors.forename: Brittany L
authors.initials: BL
authors.lastname: Cully
authors.forename: Xiaojin
authors.initials: X
authors.lastname: An
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Jian
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D042561:Vascular Endothelial Growth Factor B / Q000235:genetics* / Q000378:metabolism*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D004268:DNA-Binding Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D009124:Muscle Proteins; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors; D042561:Vascular Endothelial Growth Factor B; D000099152:Cadherin 5; C486309:TEAD4 protein, human; C467482:vascular endothelial growth factor B, mouse