title: Increased vascular endothelial growth factor expression but impaired vascular endothelial growth factor receptor signaling in the myocardium of type 2 diabetic patients with chronic coronary heart disease.
abstract: OBJECTIVE
  The aim of the present study was to evaluate the expression and the activity of vascular endothelial growth factor (VEGF) in the hearts of diabetic patients with chronic coronary heart disease (CHD).
  
  
  BACKGROUND
  Diabetes is characterized by a decreased collateral vessel formation in response to coronary ischemic events, although the role of VEGF in human diabetic macroangiopathy has not been fully investigated.
  
  
  METHODS
  Biopsies of left ventricular (LV) myocardium were obtained from 10 patients with type 2 diabetes and 10 non-diabetic patients with chronic CHD, all undergoing surgical coronary revascularization. Right ventricle myocardial samples taken from normal hearts were used as control specimens. Vascular endothelial growth factor and VEGF-receptors (flt-1 and flk-1) were evaluated by Western blot, reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR. Akt and endothelial nitric oxide synthase (eNOS) protein expression and their phosphorylated forms were also evaluated by Western blot.
  
  
  RESULTS
  Vascular endothelial growth factor, flt-1, and flk-1 messenger ribonucleic acid (mRNA) and protein expressions were increased in non-diabetic patients with CHD compared with control subjects. Remarkably, in diabetic patients, VEGF mRNA and protein levels were significantly higher, whereas flt-1, flk-1 mRNA, and protein were lower when compared with non-diabetic patients. Interestingly, phospho-flk-1 was reduced in diabetic patients compared with non-diabetic patients. As a consequence, Akt phosphorylation, eNOS protein and its phosphorylated form were significantly higher in the samples from non-diabetic patients compared with diabetic patients.
  
  
  CONCLUSIONS
  Chronic CHD in diabetic patients is characterized by an increased VEGF myocardial expression and a decreased expression of its receptors along with a down-regulation of its signal transduction. The latter could be partially responsible for the reduced neoangiogenesis in diabetic patients with ischemic cardiomyopathy.
authors.affiliation: Department of Geriatrics and Metabolic Disease, Second University of Naples, Naples, Italy. ferdinando.sasso@unina2.it
authors.forename: Ferdinando Carlo
authors.initials: FC
authors.lastname: Sasso
authors.forename: Daniele
authors.initials: D
authors.lastname: Torella
authors.forename: Ornella
authors.initials: O
authors.lastname: Carbonara
authors.forename: Georgina M
authors.initials: GM
authors.lastname: Ellison
authors.forename: Michele
authors.initials: M
authors.lastname: Torella
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Scardone
authors.forename: Claudio
authors.initials: C
authors.lastname: Marra
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Nasti
authors.forename: Raffaele
authors.initials: R
authors.lastname: Marfella
authors.forename: Domenico
authors.initials: D
authors.lastname: Cozzolino
authors.forename: Ciro
authors.initials: C
authors.lastname: Indolfi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cotrufo
authors.forename: Roberto
authors.initials: R
authors.lastname: Torella
authors.forename: Teresa
authors.initials: T
authors.lastname: Salvatore
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D002908:Chronic Disease; D003324:Coronary Artery Disease / Q000378:metabolism / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D003925:Diabetic Angiopathies; D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium; D040262:Receptors, Vascular Endothelial Growth Factor / Q000502:physiology*; D015398:Signal Transduction; D042442:Vascular Endothelial Growth Factors / Q000096:biosynthesis* / Q000502:physiology
chemical_list: D042442:Vascular Endothelial Growth Factors; D040262:Receptors, Vascular Endothelial Growth Factor