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Hyperglycemia-induced vasculopathy in the murine conceptus is mediated via reductions of VEGF-A expression and VEGF receptor activation

(2001) AMERICAN JOURNAL OF PATHOLOGY. 158(4). p.1199-1206
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Abstract
Major congenital malformations, Including those affecting the cardiovascular system, remain the leading cause of mortality and morbidity In infants of diabetic mothers. Interestingly, targeted mutations of several genes (including VEGF and VEGF receptors) and many teratogenic agents (including excess D-glucose) that give rise to embryonic lethal phenotypes during organogenesis are associated with a failure in the formation and/or maintenance of a functional vitelline circulation, Given the similarities in the pathology of the abnormal vitelline circulation in many of these conditions, we hypothesized that the hyperglycemic insult present hn diabetes could cause the resultant abnormalitles in the vitelline circulation by affecting VEGF/VEGF receptor signaling pathway(s). In this study we report that hyperglycemic insult results in reduced levels of VEGF-A in the conceptus, which in turn, leads to abnormal VEGF receptor signaling, ultimately resulting in embryonic (vitelline) vasculopathy. These findings and our observation that addition of exogenous rVEGF-A(165) within a defined concentration range blunts the hyperglycemia-induced vasculopathy in the conceptus support the concept that VEGF levels can be modulated by glucose levels. In addition, these findings may ultimately lead to novel therapeutic approaches for the treatment of selected congenital cardiovascular abnormalities associated with diabetes.
Keywords
CELL-ADHESION MOLECULE-1, TYROSINE PHOSPHORYLATION STATE, ENDOTHELIAL GROWTH-FACTOR, IN-VITRO, DIABETIC EMBRYOPATHY, VASCULAR DEVELOPMENT, FLK-1 RECEPTOR, VASCULOGENESIS, FLT-1, DIFFERENTIATION

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Citation

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Chicago
Pinter, E, Jody Haigh, A Nagy, and JA Madri. 2001. “Hyperglycemia-induced Vasculopathy in the Murine Conceptus Is Mediated via Reductions of VEGF-A Expression and VEGF Receptor Activation.” American Journal of Pathology 158 (4): 1199–1206.
APA
Pinter, E., Haigh, J., Nagy, A., & Madri, J. (2001). Hyperglycemia-induced vasculopathy in the murine conceptus is mediated via reductions of VEGF-A expression and VEGF receptor activation. AMERICAN JOURNAL OF PATHOLOGY, 158(4), 1199–1206.
Vancouver
1.
Pinter E, Haigh J, Nagy A, Madri J. Hyperglycemia-induced vasculopathy in the murine conceptus is mediated via reductions of VEGF-A expression and VEGF receptor activation. AMERICAN JOURNAL OF PATHOLOGY. 2001;158(4):1199–206.
MLA
Pinter, E, Jody Haigh, A Nagy, et al. “Hyperglycemia-induced Vasculopathy in the Murine Conceptus Is Mediated via Reductions of VEGF-A Expression and VEGF Receptor Activation.” AMERICAN JOURNAL OF PATHOLOGY 158.4 (2001): 1199–1206. Print.
@article{1202135,
  abstract     = {Major congenital malformations, Including those affecting the cardiovascular system, remain the leading cause of mortality and morbidity In infants of diabetic mothers. Interestingly, targeted mutations of several genes (including VEGF and VEGF receptors) and many teratogenic agents (including excess D-glucose) that give rise to embryonic lethal phenotypes during organogenesis are associated with a failure in the formation and/or maintenance of a functional vitelline circulation, Given the similarities in the pathology of the abnormal vitelline circulation in many of these conditions, we hypothesized that the hyperglycemic insult present hn diabetes could cause the resultant abnormalitles in the vitelline circulation by affecting VEGF/VEGF receptor signaling pathway(s). In this study we report that hyperglycemic insult results in reduced levels of VEGF-A in the conceptus, which in turn, leads to abnormal VEGF receptor signaling, ultimately resulting in embryonic (vitelline) vasculopathy. These findings and our observation that addition of exogenous rVEGF-A(165) within a defined concentration range blunts the hyperglycemia-induced vasculopathy in the conceptus support the concept that VEGF levels can be modulated by glucose levels. In addition, these findings may ultimately lead to novel therapeutic approaches for the treatment of selected congenital cardiovascular abnormalities associated with diabetes.},
  author       = {Pinter, E and Haigh, Jody and Nagy, A and Madri, JA},
  issn         = {0002-9440},
  journal      = {AMERICAN JOURNAL OF PATHOLOGY},
  keyword      = {CELL-ADHESION MOLECULE-1,TYROSINE PHOSPHORYLATION STATE,ENDOTHELIAL GROWTH-FACTOR,IN-VITRO,DIABETIC EMBRYOPATHY,VASCULAR DEVELOPMENT,FLK-1 RECEPTOR,VASCULOGENESIS,FLT-1,DIFFERENTIATION},
  language     = {eng},
  number       = {4},
  pages        = {1199--1206},
  title        = {Hyperglycemia-induced vasculopathy in the murine conceptus is mediated via reductions of VEGF-A expression and VEGF receptor activation},
  volume       = {158},
  year         = {2001},
}

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