title: VEGF is indirectly associated with NO production and acutely increases in response to hyperglycaemia(1).
abstract: 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.
  
  
  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.
authors.affiliation: Human Nutrition Research Centre, Institute for Ageing and Health, Newcastle University, Newcastle On Tyne, UK. mario.siervo@newcastle.ac.uk
authors.forename: Mario
authors.initials: M
authors.lastname: Siervo
authors.forename: Virginia
authors.initials: V
authors.lastname: Tomatis
authors.forename: Blossom C M
authors.initials: BC
authors.lastname: Stephan
authors.forename: Martin
authors.initials: M
authors.lastname: Feelisch
authors.forename: Les J C
authors.initials: LJ
authors.lastname: Bluck
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D008962:Models, Theoretical; D009569:Nitric Oxide / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D014280:Triglycerides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide