title: VEGF levels in plasma in relation to platelet activation, glycemic control, and microvascular complications in type 1 diabetes.
abstract: OBJECTIVE
  Increased levels of vascular endothelial growth factor (VEGF) in human plasma samples have suggested that circulating VEGF is a cause of endothelial dysfunction in diabetes mellitus. However, artificial release of VEGF from platelets as a source of VEGF in plasma samples, as also occurs in serum samples, has not been ruled out in these studies.
  
  
  METHODS
  We determined VEGF levels in plasma collected in both citrate and PECT, a medium that inactivates platelets, in a cross-sectional cohort of 21 healthy subjects and 64 patients with type 1 diabetes. In addition, we evaluated whether VEGF levels in both types of plasma correlated with the presence of diabetes, glycemic control, markers of in vivo or ex vivo platelet activation, and degree of diabetic retinopathy and nephropathy.
  
  
  RESULTS
  VEGF levels were invariably low in PECT plasma of both nondiabetic and diabetic subjects and were unrelated to any other diabetes-related variable studied. In contrast, VEGF levels in citrate plasma were 150% higher in diabetic patients than in control subjects and correlated with diabetes-related variables. Multiple linear regression analysis showed that levels of platelet factor 4, a marker for ex vivo platelet activation, and HbA1c were the independent predictors of VEGF levels in citrate plasma. Platelet activation, in vivo and ex vivo, was similar in diabetic persons and control subjects.
  
  
  CONCLUSIONS
  Like serum, citrate plasma is not suitable for reliable measurements of circulating VEGF. The low levels of VEGF in vivo, as represented by measurements in PECT plasma in our study, do not support a role of circulating VEGF in endothelial dysfunction in type 1 diabetes. Higher levels of VEGF in citrate plasma samples of diabetic persons do not represent the in vivo situation, but mainly originate from higher artificial ex vivo release from platelets correlating with the degree of glycemic control.
authors: Ocular Angiogenesis Group, Departments of Ophthalmology and Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. r.schlingemann@amc.uva.nl
authors: Reinier O
authors: RO
authors: Schlingemann
authors: Cornelis J F
authors: CJ
authors: Van Noorden
authors: Mattheus J M
authors: MJ
authors: Diekman
authors: Anna
authors: A
authors: Tiller
authors: Joost C M
authors: JC
authors: Meijers
authors: Pieter
authors: P
authors: Koolwijk
authors: Wilmar M
authors: WM
authors: Wiersinga
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D015539:Platelet Activation / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D042461:Vascular Endothelial Growth Factor A