title: Overexpression of vascular endothelial growth factor 165 (VEGF165) protects cardiomyocytes against doxorubicin-induced apoptosis.
abstract: Doxorubicin (Dox) has been employed in cancer chemotherapy for a few decades. However its clinical application became restricted because of dose-dependent cardiomyopathy. Recent studies suggest that Dox-induced cardiomyocyte apoptosis is a primary cause of cardiac damage. Vascular endothelial growth factor (VEGF) is a major factor for endothelial cell survival and angiogenesis. We have previously shown that VEGF165 significantly attenuates oxidative stress-induced cardiomyocytes apoptosis. We hypothesized that VEGF165 will protect the cardiomyocytes from Dox-induced apoptosis. to evaluate our hypothesis, we transfected cardiomyocytes H9c2 with adenovirus expressing VEGF165 24 hours before the cells were challenged with Dox at a concentration of 2 µm. Cardiomyocyte apoptosis was evaluated by Annexin V-FITC staining and by Western blot detection of cleaved caspase-3. The hypothesis was confirmed, and the protective mechanisms involve the inhibition of death receptor-mediated apoptosis and up-regulation of the prosurvival Akt/Nf-κb/bcl-2 signaling pathway.
authors.affiliation: Department of Pathology, Shandong University School of Medicine, 44# Wenhuaxi Road, Jinan, Shandong, 250012, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Chen
authors.forename: Gengyin
authors.initials: G
authors.lastname: Zhou
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhu
authors.forename: Xian
authors.initials: X
authors.lastname: Liu
authors.forename: Tuanzhu
authors.initials: T
authors.lastname: Ha
authors.forename: J L
authors.initials: JL
authors.lastname: Kelley
authors.forename: R L
authors.initials: RL
authors.lastname: Kao
authors.forename: D L
authors.initials: DL
authors.lastname: Williams
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002478:Cells, Cultured; D004317:Doxorubicin / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: C505535:Fadd protein, rat; D053200:Fas-Associated Death Domain Protein; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D004317:Doxorubicin; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D053181:Caspase 8