title: Hyperglycaemia is associated with impaired vasa vasorum neovascularization and accelerated atherosclerosis in apolipoprotein-E deficient mice.
abstract: OBJECTIVE
  A direct correlation between blood glucose levels and the microvascular complications of diabetes is well established. However, the effects of hyperglycaemia on the vasa vasorum, a microvascular network which surrounds and supplies the walls of large arteries, is not known. The objective of this study is to investigate the effects of hyperglycaemia on the vasa vasorum and to examine correlations between these effects and the development of atherosclerosis in a mouse model.
  
  
  METHODS
  The micro- and macrovascular effects of hyperglycaemia were examined in streptozotocin-injected apolipoprotein-E deficient (ApoE(-/-)) mice. Retina and aortic sinus were isolated from hyperglycaemic mice and normoglycaemic controls at 5-20 weeks of age. Retinal and vasa vasorum microvessel densities were quantified and correlated to atherosclerotic lesion development. The expression levels of pro-angiogenic factors including vascular endothelial growth factor (VEGF) and VEGF receptor 2 were examined.
  
  
  RESULTS
  In normoglycaemic ApoE(-/-) mice atherogenesis is associated with vasa vasorum expansion, which likely corresponds to the increasing blood supply demands of the thickening artery wall. In hyperglycaemic ApoE(-/-) mice there is no significant neovascularization of the vasa vasorum, despite the fact that lesions are significantly larger. This defect may result from a localized deficiency in VEGF.
  
  
  CONCLUSIONS
  These findings are the first evidence that hyperglycaemia alters the structure of the vasa vasorum. Such microvascular changes directly correlate, and may contribute to, the development and progression of atherosclerosis in hyperglycaemic ApoE-deficient mice.
authors: Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada. veermankj@gmail.com
authors: K J
authors: KJ
authors: Veerman
authors: D E
authors: DE
authors: Venegas-Pino
authors: Y
authors: Y
authors: Shi
authors: M I
authors: MI
authors: Khan
authors: H C
authors: HC
authors: Gerstein
authors: G H
authors: GH
authors: Werstuck
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000378:metabolism* / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D006943:Hyperglycemia / Q000378:metabolism* / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D055806:Microvessels / Q000473:pathology; D009389:Neovascularization, Pathologic; D012160:Retina / Q000473:pathology; D012850:Sinus of Valsalva / Q000473:pathology; D014651:Vasa Vasorum / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D001786:Blood Glucose; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2