title: Potential mechanism for endothelial progenitor cell therapy in acute myocardial infarction: Activation of VEGF- PI3K/Akte-NOS pathway.
abstract: Mounting evidence suggests that transplanting endothelial progenitor cells (EPCs) into the myocardium improves cardiac function after myocardial infarction (MI). However, the mechanism remains controversial. The aim of this study was to investigate the role played by the VEGF- PI3K/Akt-eNOS pathway in EPC-based cell therapy. Cultured EPCs, which were identified by morphology, function, and cell surface markers, were transplanted into the border zone after left anterior descending coronary artery ligation in mice. Expression levels of VEGF, p-Akt, and eNOS in the border zone were elevated three days after EPC transplantation. EPC therapy enhanced expression of VEGFR-2, increased microvessel density, and reduced interstitial fibrosis in the border zone after MI. The left ventricular fractional shortening was increased and the left ventricular diameter was smaller after EPC treatment. Wortmannin inhibited the expression of p-Akt and was associated with decreased cardiac function. Our study suggests that EPC transplantation improves cardiac function after MI, mediated at least partially by activation of the VEGF -PI3K/Akt-eNOS pathway.
authors.affiliation: Department of Cardiology, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, P.R. China; phone/fax: 025-80863022, e mail: jssmed@sina.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Shisen
authors.initials: S
authors.lastname: Jiang
authors.forename: Ruoyu
authors.initials: R
authors.lastname: Hu
authors.forename: Lei
authors.initials: L
authors.lastname: Lv
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004452:Echocardiography; D042783:Endothelial Cells / Q000637:transplantation*; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D051379:Mice; D009203:Myocardial Infarction / Q000378:metabolism / Q000628:therapy*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D019869:Phosphatidylinositol 3-Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2; D051058:Oncogene Protein v-akt
keywords: Akt; VEGF; eNOS; endothelial progenitor cells; neovascularization