Overexpression of Vascular Endothelial Growth Factor 165 (VEGF165) Protects Cardiomyocytes Against Doxorubicin-Induced Apoptosis

• Published in: Journal of chemotherapy (Florence) 2010-12, Vol.22 (6), p.402-406
• Main Authors: Chen, Tingting, Zhou, Gengyin, Zhu, Quan, Liu, Xian, Ha, Tuanzhu, Kelley, J.L., Kao, R.L., Williams, D.L., Li, Chuanfu
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; cardiomyocytes; Caspase 3 - metabolism; Caspase 8 - metabolism; Cells, Cultured; doxorubicin; Doxorubicin - pharmacology; Endothelial Cells - drug effects; Fas-Associated Death Domain Protein - metabolism; Medical sciences; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; NF-kappa B - metabolism; Oxidative Stress - drug effects; Oxidative Stress - physiology; Pharmacology. Drug treatments; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Signal Transduction - drug effects; Transfection; Up-Regulation - genetics; vascular endothelial growth factor 165 (VEGF165); Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 1120-009X; 1973-9478
• DOI: 10.1179/joc.2010.22.6.402

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 VEGF 165 significantly attenuates oxidative stress-induced cardiomyocytes apoptosis. We hypothesized that VEGF 165 will protect the cardiomyocytes from Dox-induced apoptosis. to evaluate our hypothesis, we transfected cardiomyocytes H9c2 with adenovirus expressing VEGF 165 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/NFB/Bcl-2 signaling pathway.