Molecular Medicine

, Volume 14, Issue 11–12, pp 705–714 | Cite as

Angiogenesis and Diabetes: Different Responses to Pro-Angiogenic Factors in the Chorioallantoic Membrane Assay

  • Giovana S. Di Marco
  • Antoine Alam
  • Frédéric Dol
  • Pierre Corvol
  • Jean-Marie Gasc
  • Etienne Larger
Research Article


Hyperglycemia induces defects in angiogenesis without alteration in the expression of major vascular growth factors in the chicken chorioallantoic membrane (CAM) model. A direct negative effect of hyperglycemia on angiogenesis may participate in failures of “therapeutic angiogenesis” trials. Here, we tested the hypothesis that the response to pro-angiogenic molecules such as angiotensin-converting enzyme (ACE), endothelin-1 (ET-1), and vascular endothelial growth factor-A (VEGF) is altered by hyperglycemia. Transfected (Chinese hamster ovary (CHO) or human embryonic kidney (HEK)) cells overexpressing ACE, ET-1, or VEGF were deposed onto the CAM of hyperglycemic or control embryos. The proangiogenic effect was evaluated 3 d later by angiography and histological analyses. Gene expression in response to these factors was assessed by in situ hybridization. Only VEGF overexpression evoked a proangiogenic response in the CAM from hyperglycemic embryos, upregulating the expression of endogenous VEGF, VEGF-R2, and Tie-2, all of them related to activation of endothelial cells. In conclusion, in a model where hyperglycemia does not alter the major vascular growth factor expression, the negative effect of diabetes on capillary density was overcome only by VEGF overexpression, whereas responses to other vasoactive peptides were practically abolished under hyperglycemic conditions.



The authors thank P Mayeux, INSERM, Paris, for the gift of the antibody to hEPO. Thanks also to M Brand, M Clemessy, and MT Morin for their excellent assistance. GS Di Marco was supported by a fellowship from the Foundation pour la Recherche Médicale (FRM), France.


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Copyright information

© Feinstein Institute for Medical Research 2008

Authors and Affiliations

  • Giovana S. Di Marco
    • 1
  • Antoine Alam
    • 2
  • Frédéric Dol
    • 2
  • Pierre Corvol
    • 1
  • Jean-Marie Gasc
    • 1
  • Etienne Larger
    • 1
  1. 1.Institut National de la Santé et de la Recherche Médicale (INSERM) U833Collège de FranceParisFrance
  2. 2.Angiogenesis and Thrombosis DepartmentSanofi-Aventis R&DToulouseFrance

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