Dataset Information

Vascular endothelial growth factor, its soluble receptor, and hepatocyte growth factor: clinical and genetic correlates and association with vascular function.

ABSTRACT:

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.

SUBMITTER: Lieb W

PROVIDER: S-EPMC2721714 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Publications

Vascular endothelial growth factor, its soluble receptor, and hepatocyte growth factor: clinical and genetic correlates and association with vascular function.

Lieb Wolfgang W Safa Radwan R Benjamin Emelia J EJ Xanthakis Vanessa V Yin Xiaoyan X Sullivan Lisa M LM Larson Martin G MG Smith Holly M HM Vita Joseph A JA Mitchell Gary F GF Sawyer Douglas B DB Vasan Ramachandran S RS

European heart journal 20090217 9

<h4>Aims</h4>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.<h4>Methods and results</h4>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 measure ...[more]

PMID: 19223316

Similar Datasets

Project description:BackgroundReceptor signaling is central to vascular endothelial function and is dysregulated in vascular diseases such as atherosclerosis and pulmonary arterial hypertension (PAH). Signaling pathways involved in endothelial function include vascular endothelial growth factor receptors (VEGFRs) and G protein-coupled receptors, which classically activate distinct intracellular signaling pathways and responses. The mechanisms that regulate these signaling pathways have not been fully elucidated and it is unclear what nodes for cross talk exist between these diverse signaling pathways. For example, multifunctional β-arrestin (ARRB) adapter proteins are best known as regulators of G protein-coupled receptor signaling, but their role at other receptors and their physiological importance in the setting of vascular disease are unclear.MethodsWe used a combination of human samples from PAH, human microvascular endothelial cells from lung, and Arrb knockout mice to determine the role of ARRB1 in endothelial VEGFR3 signaling. In addition, a number of biochemical analyses were performed to determine the interaction between ARRB1 and VEGFR3, signaling mediators downstream of VEGFR3, and the internalization of VEGFR3.ResultsExpression of ARRB1 and VEGFR3 was reduced in human PAH, and the deletion of Arrb1 in mice exposed to hypoxia led to worse PAH with a loss of VEGFR3 signaling. Knockdown of ARRB1 inhibited VEGF-C-induced endothelial cell proliferation, migration, and tube formation, along with reduced VEGFR3, Akt, and endothelial nitric oxide synthase phosphorylation. This regulation was mediated by direct ARRB1 binding to the VEGFR3 kinase domain and resulted in decreased VEGFR3 internalization.ConclusionsOur results demonstrate a novel role for ARRB1 in VEGFR regulation and suggest a mechanism for cross talk between G protein-coupled receptors and VEGFRs in PAH. These findings also suggest that strategies to promote ARRB1-mediated VEGFR3 signaling could be useful in the treatment of pulmonary hypertension and other vascular disease.

Dataset Information

Vascular endothelial growth factor, its soluble receptor, and hepatocyte growth factor: clinical and genetic correlates and association with vascular function.

Aims

Methods and results

Conclusion

Publications

Vascular endothelial growth factor, its soluble receptor, and hepatocyte growth factor: clinical and genetic correlates and association with vascular function.

Similar Datasets

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