title: Differential modulation of angiogenesis by advanced glycation end products.
abstract: Divergent angiogenic responses occur in different organs in a diabetic state. Many of the pathological effects were mediated by the advanced glycation end products (AGEs) of non-enzymatically glycated molecules. Investigations were carried out using different angiogenic model systems to examine whether the angiogenic response to AGEs is influenced by the cellular microenvironment. AGE-albumin increased angiogenesis in chick chorioallantoic membrane (CAM). It also increased sprouting in rat aortic rings and the expression of angiogenic markers CD31 and E-selectin and the angiogenic growth factor, vascular endothelial growth factor (VEGF) in human umbilical vein endothelial cells (HUVECs) in culture, suggesting a proangiogenic effect. But in a serum-supplemented condition, AGE-albumin inhibited aortic sprouting and expression of angiogenic markers and VEGF production by HUVECs, suggesting an antiangiogenic effect in the presence of serum. Blocking of the AGE effect by the antioxidants, N-acetyl cysteine and ascorbic acid, suggested that the AGE effect involved oxidant stress. Reversal of the AGE effect by LY 294 002, an inhibitor of the Akt pathway and increased phosphorylation of Akt in cells maintained in serum-free medium, suggested the involvement of the Akt pathway in mediating the AGE effect; such an effect was absent in a serum-supplemented condition. These opposing effects of AGE-albumin on angiogenesis in the presence and absence of serum suggested that the AGE accumulated in a hyperglycemic condition can affect angiogenesis depending on the microenvironment of the cells.
authors.affiliation: Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, Kerala 695 581, India.
authors.forename: Manju S
authors.initials: MS
authors.lastname: Devi
authors.forename: Perumana R
authors.initials: PR
authors.lastname: Sudhakaran
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001205:Ascorbic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002867:Chromones / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000503:physiopathology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000502:physiology
chemical_list: D000975:Antioxidants; D002867:Chromones; D017127:Glycation End Products, Advanced; D009025:Morpholines; D042461:Vascular Endothelial Growth Factor A; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt; D001205:Ascorbic Acid; D000111:Acetylcysteine