European Heart Journal Advance Access originally published online on February 17, 2009
European Heart Journal 2009 30(9):1121-1127; doi:10.1093/eurheartj/ehp007
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Vascular endothelial growth factor, its soluble receptor, and hepatocyte growth factor: clinical and genetic correlates and association with vascular function
1 Framingham Heart Study, 73 Mount Wayte Ave., Framingham, MA 01702-5803, USA
2 Division of Graduate Medical Sciences, Boston University, Boston, MA, USA
3 Sections of Preventive Medicine and Cardiology, Evans Memorial Department of Medicine, Boston University, School of Medicine, Boston, MA, USA
4 Department of Biostatisatics, Boston University, School of Public Health, Boston, MA, USA
5 Department of Mathematics, Boston University, Boston, MA, USA
6 Cardiovascular Division, Vanderbilt University, Nashville, TN, USA
7 Cardiovascular Engineering Inc., Norwood, MA, USA
Received 28 May 2008; revised 1 December 2008; accepted 8 January 2009; online publish-ahead-of-print 17 February 2009.
* Corresponding author. Tel: +1 508 935 3450, Fax: +1 508 626 1262, Email: vasan{at}bu.edu
Aims: 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.
Methods and 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.
Conclusion: 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.
Key Words: Vascular growth factors • VEGF • SFlt-1 • HGF • Vascular function • Heritability • Metabolic syndrome
These authors contributed equally.