The material presented in this manuscript is original and has not been submitted for publication elsewhere while under consideration for European Journal of Clinical Investigation.
VEGF is indirectly associated with NO production and acutely increases in response to hyperglycaemia†
Article first published online: 8 MAY 2012
© 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation
European Journal of Clinical Investigation
Volume 42, Issue 9, pages 967–973, September 2012
How to Cite
Siervo, M., Tomatis, V., Stephan, B. C. M., Feelisch, M. and Bluck, L. J. C. (2012), VEGF is indirectly associated with NO production and acutely increases in response to hyperglycaemia. European Journal of Clinical Investigation, 42: 967–973. doi: 10.1111/j.1365-2362.2012.02684.x
- Issue published online: 10 AUG 2012
- Article first published online: 8 MAY 2012
- Accepted manuscript online: 12 APR 2012 01:47PM EST
- Received 3 December 2011; accepted 10 April 2012
- nitric oxide;
- vascular endothelial growth factor
Eur J Clin Invest 2012; 42 (9): 967–973
Background Increased levels of vascular endothelial growth factor (VEGF) have been observed in patients with metabolic syndrome (MetS). Nitric oxide (NO) formation is reduced in MetS, but its relationship to VEGF production remains poorly defined. We evaluated the association between VEGF/NO synthesis and insulin sensitivity in obese subjects and investigated the secretory response of VEGF to an acute elevation of glucose.
Materials and methods Seven healthy normal-weight subjects, seven obese subjects without MetS and seven obese subjects with MetS were recruited. Anthropometry, body composition and cardiometabolic functions (blood pressure, glucose, insulin, triglycerides, total cholesterol, HDL-C and VEGF) were measured, and a novel stable isotope method was used to assess in vivo rates of NO production. A frequent sampling intravenous glucose tolerance test was performed to study the dynamics of VEGF release.
Results Fasting VEGF levels were significantly higher in the two obese groups compared to the control group (P for trend = 0·02), but the difference was not significant after adjustment for age. Vascular endothelial growth factor levels were associated with systolic blood pressure (ρ = 0·54; P = 0·01) and NO production (ρ = −0·44; P = 0·04). Vascular endothelial growth factor levels increased in response to acute hyperglycaemia in normal-weight and obese subjects (P < 0·001).
Conclusions Vascular endothelial growth factor levels rapidly increase during hyperglycaemia and are inversely related to NO production at steady state. The potential link between the acute secretion of VEGF and atherosclerotic risk in subjects with poorly controlled glycaemia as well as the potential of lowering elevated VEGF levels by increasing NO production and/or availability warrants further investigation.