title: Vascular endothelial growth factor, its soluble receptor, and hepatocyte growth factor: clinical and genetic correlates and association with vascular function.
abstract: OBJECTIVE
  Growth factors play an important role in regulating vascular function. Data are limited regarding clinical and genetic correlates of endothelial growth factors and their associations with vascular function.
  
  
  RESULTS
  We evaluated clinical and genetic correlates of circulating vascular endothelial growth factor A (VEGF), its soluble receptor sFlt-1, and hepatocyte growth factor (HGF) in 3754 Framingham Study participants. We also related the growth factors to measures of brachial artery function. Serum VEGF and HGF were higher and sFLt-1 was lower in women and smokers. VEGF and HGF were associated positively with body mass index; both displayed strong positive associations with the metabolic syndrome (P < 0.001) and its components. The heritabilities of VEGF, sFlt-1, and HGF were 78, 13, and 38%, respectively. VEGF and HGF were related positively to baseline brachial diameter (P < 0.01) and to baseline mean flow velocity (P < 0.001) in age- and sex-adjusted models, but the multivariable models failed to reach significance. None of the growth factors were related to flow-mediated dilation.
  
  
  CONCLUSIONS
  In our community-based sample, circulating VEGF and HGF demonstrated high heritabilities and a sexual dimorphism. Increased angiogenesis and greater endothelial cell turnover may underlie associations of these growth factors with risk factors including smoking.
authors.affiliation: Framingham Heart Study, 73 Mount Wayte Ave., Framingham, MA 01702-5803, USA.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.forename: Radwan
authors.initials: R
authors.lastname: Safa
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.forename: Vanessa
authors.initials: V
authors.lastname: Xanthakis
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yin
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Sullivan
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Holly M
authors.initials: HM
authors.lastname: Smith
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Vita
authors.forename: Gary F
authors.initials: GF
authors.lastname: Mitchell
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Sawyer
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D003430:Cross-Sectional Studies; D005260:Female; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010290:Parents; D010375:Pedigree; D019655:Quantitative Trait, Heritable; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1