title: Acute hypoxia decreases plasma VEGF concentration in healthy humans.
abstract: Vascular endothelial growth factor (VEGF) is known to be upregulated by hypoxia in vitro. However, in vivo data about VEGF regulation in chronic hypoxic diseases are conflicting. We investigated the effects of hypoxia on plasma VEGF concentration in healthy subjects. To control known confounders, such as insulin, glucose concentrations, or exercise, hypoxic effects on VEGF were studied during experimentally clamping glucose concentrations at rest. In a double-blind crossover study design, we induced hypoxia for 30 min by decreasing oxygen saturation to 75% (vs. normoxic control) in 14 healthy men. Plasma VEGF concentration was determined at baseline, immediately after hypoxia had ended, and after a further 150 min. Levels of its soluble (s)Flt-1 receptor were assessed at baseline and at the end of the clamp. In parallel, catecholamine and cortisol levels were monitored. To investigate potential effects of glucose administration on the release of VEGF, we performed a third session, reducing glucose infusion for 30 min while serum insulin was held stable thereby inducing hypoglycemia. Hypoxia decreased VEGF levels compared with the normoxic control (P<0.05). VEGF concentrations increased during hypoglycemia (P<0.02) but were comparable to the normoglycemic control at the end of the clamp (P>0.80). sFlt-1 receptor concentration remained unchanged during hypoxia and hypoglycemia compared with control (both P>0.4). Epinephrine concentration (P<0.01) increased upon hypoxia, whereas norepinephrine and cortisol did not change. Contrary to in vitro studies, in healthy humans hypoxia decreases plasma VEGF concentration, suggesting that systemic VEGF concentration may be differently regulated than the expression on cellular basis.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Luebeck, Luebeck, Germany. Oltmanns@medinf.mu-luebeck.de
authors.forename: Kerstin M
authors.initials: KM
authors.lastname: Oltmanns
authors.forename: Hartmut
authors.initials: H
authors.lastname: Gehring
authors.forename: Sebastian
authors.initials: S
authors.lastname: Rudolf
authors.forename: Bernd
authors.initials: B
authors.lastname: Schultes
authors.forename: Claudia
authors.initials: C
authors.lastname: Hackenberg
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schweiger
authors.forename: Jan
authors.initials: J
authors.lastname: Born
authors.forename: Horst L
authors.initials: HL
authors.lastname: Fehm
authors.forename: Achim
authors.initials: A
authors.lastname: Peters
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood; D015309:Glucose Clamp Technique; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D000860:Hypoxia / Q000097:blood* / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010100:Oxygen / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
chemical_list: D001786:Blood Glucose; D007328:Insulin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D010100:Oxygen; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine