title: Decreased cardiac expression of vascular endothelial growth factor and its receptors in insulin-resistant and diabetic States: a possible explanation for impaired collateral formation in cardiac tissue.
abstract: BACKGROUND
  Inadequate angiogenic response to ischemia in the myocardium of diabetic patients could result in poor collateral formation. Yet, excessive neovascularization in the retina causes proliferative diabetic retinopathy. Since vascular endothelial growth factor (VEGF) is the major angiogenic factor expressed in response to hypoxia, we have characterized expression of VEGF and its receptors in retina, renal glomeruli, aorta, and myocardium in insulin-resistant and diabetic states. Methods and Results- The expression of mRNA and protein for VEGF and its receptors, VEGF-R1 and VEGF-R2, in the myocardium was decreased significantly by 40% to 70% in both diabetic and insulin-resistant nondiabetic rats. Twofold reductions in VEGF and VEGF-R2 were observed in ventricles from diabetic patients compared with nondiabetic donors. In contrast, expression of VEGF and its receptors were increased 2-fold in retina and glomeruli from diabetic or insulin-resistant rats. Insulin treatment of diabetic rats normalized changes in both cardiac and microvascular tissues. Insulin increased VEGF mRNA expression in cultured rat neonatal cardiac myocytes.
  
  
  CONCLUSIONS
  The results documented for the first time that differential regulation of VEGF and its receptors exist between microvascular and cardiac tissues, which can be regulated by insulin. These results provide a potential explanation for concomitant capillary leakage and neovascularization in the retina and inadequate collateral formation in the myocardium of insulin-resistant and diabetic patients.
authors.affiliation: Research Division, Beetham Eye Institute, Joslin Diabetes Center, Boston, Massachusetts, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Chou
authors.forename: Izumi
authors.initials: I
authors.lastname: Suzuma
authors.forename: Kerrie J
authors.initials: KJ
authors.lastname: Way
authors.forename: Darren
authors.initials: D
authors.lastname: Opland
authors.forename: Allen C
authors.initials: AC
authors.lastname: Clermont
authors.forename: Keiko
authors.initials: K
authors.lastname: Naruse
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Suzuma
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Bowling
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Vlahos
authors.forename: Lloyd Paul
authors.initials: LP
authors.lastname: Aiello
authors.forename: George L
authors.initials: GL
authors.lastname: King
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003097:Collateral Circulation; D003326:Coronary Circulation; D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D007678:Kidney Glomerulus / Q000378:metabolism; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D009765:Obesity; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor; D012160:Retina / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D007328:Insulin; D008222:Lymphokines; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor