title: Plasma vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 in diabetes: implications for cardiovascular risk and effects of multifactorial intervention.
abstract: OBJECTIVE
  Vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-1 and Ang-2 are mediators of angiogenesis. More recent data suggest that the balance between these growth factors may affect vascular endothelial integrity. Because diabetes is closely associated with endothelial perturbation, we studied plasma levels of these angiogenic growth factors in patients with diabetes; their relationship with glycemia, inflammation, and endothelial damage/dysfunction; and the effect of intensified cardiovascular risk management.
  
  
  METHODS
  We measured plasma VEGF, Ang-1, and Ang-2 alongside plasma von Willebrand factor (vWf) and urine albumin-to-creatinine ratio (marking endothelial damage/dysfunction) and interleukin (IL)-6 in 94 patients (38 with overt cardiovascular disease [CVD]) with diabetes and 34 normal control subjects.
  
  
  RESULTS
  Plasma vWf (P=0.009), IL-6 (P <0.001), VEGF (P=0.001), and Ang-2 (P=0.001), but not Ang-1 (P=0.635), were higher in diabetic patients with and without CVD than in control subjects. On multivariate analysis, HbA1c was an independent predictor of plasma VEGF (P=0.032) and Ang-2 (P=0.015). Of the 94 patients, a subgroup of 33 patients with and 31 patients without CVD participated in a year of intensified cardiovascular risk management. HbA1c and LDL cholesterol reduced significantly with treatment, along with associated reductions in plasma vWf and VEGF in both groups (P <0.001). Ang-2 decreased (P <0.001) only in patients without CVD. There were no significant changes in plasma IL-6 levels in both groups.
  
  
  CONCLUSIONS
  Plasma Ang-2 (but not Ang-1), like VEGF levels, are selectively elevated in patients with diabetes and are associated with indexes of endothelial damage/dysfunction, regardless of vascular disease. Intensive multifactorial intervention is associated with reductions in plasma VEGF, vWf, and (in patients without CVD) Ang-2 levels, possibly reflecting an improved vascular profile with treatment.
authors.affiliation: Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, B18 7QH, UK.
authors.forename: Hoong Sern
authors.initials: HS
authors.lastname: Lim
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Blann
authors.forename: Aun Yeong
authors.initials: AY
authors.lastname: Chong
authors.forename: Bethan
authors.initials: B
authors.lastname: Freestone
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000368:Aged; D000419:Albuminuria; D042683:Angiopoietin-1 / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000652:urine; D003925:Diabetic Angiopathies / Q000097:blood*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D009389:Neovascularization, Pathologic / Q000097:blood; D012016:Reference Values; D012044:Regression Analysis; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015415:Biomarkers; D006442:Glycated Hemoglobin; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor