OBJECTIVES: 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.
OBJECTIVES: The aim of the present study was to evaluate the expression and the activity of vascular endothelial growth factor (VEGF) in the hearts of diabeticpatients 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 humandiabetic 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-diabeticpatients 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-diabeticpatients with CHD compared with control subjects. Remarkably, in diabeticpatients, VEGF mRNA and protein levels were significantly higher, whereas flt-1, flk-1 mRNA, and protein were lower when compared with non-diabeticpatients. Interestingly, phospho-flk-1 was reduced in diabeticpatients compared with non-diabeticpatients. As a consequence, Akt phosphorylation, eNOS protein and its phosphorylated form were significantly higher in the samples from non-diabeticpatients compared with diabeticpatients. CONCLUSIONS: Chronic CHD in diabeticpatients 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 diabeticpatients with ischemic cardiomyopathy.
Authors: H N Ashiqur Rahman; Hao Wu; Yunzhou Dong; Satish Pasula; Aiyun Wen; Ye Sun; Megan L Brophy; Kandice L Tessneer; Xiaofeng Cai; John McManus; Baojun Chang; Sukyoung Kwak; Negar S Rahman; Wenjia Xu; Conrad Fernandes; John Michael Mcdaniel; Lijun Xia; Lois Smith; R Sathish Srinivasan; Hong Chen Journal: Circ Res Date: 2016-02-15 Impact factor: 17.367
Authors: Michael Simons; Kari Alitalo; Brian H Annex; Hellmut G Augustin; Craig Beam; Bradford C Berk; Tatiana Byzova; Peter Carmeliet; William Chilian; John P Cooke; George E Davis; Anne Eichmann; M Luisa Iruela-Arispe; Eli Keshet; Albert J Sinusas; Christiana Ruhrberg; Y Joseph Woo; Stefanie Dimmeler Journal: Circ Res Date: 2015-04-30 Impact factor: 17.367