Enhancement of vascular formation but not improvement of ventricular function of infarcted rat hearts by a high dose of adenovirus-carried VEGF transgene.
The purpose of this study was to examine the influence of adenovirus-carried VEGF165 transgene at 5 x 10(10) pfu (Ad-VEGF) on vascular formation, cardiac geometry and ventricular function in infarcted hearts of the rat and to explore the mechanism of Ad-VEGF-mediated actions on ventricular function by quantitative proteomic analysis. Seven days after coronary occlusion, intramyocardial injection with normal saline (vehicle control), adenovirus-carried beta-galactosidase gene (Ad-LacZ, vector control) or Ad-VEGF to infarcted hearts was conducted. Seven days after intramyocardial injection, ventricular function, cardiac morphology and vascular density were assessed after echocardiographic analysis and immunohistological staining. One dimensional gel electrophoresis coupled with stable isotope dimethyl labeling and LC/MS/MS was used to quantify the abundance ratio of each protein pair in Ad-VEGF- and Ad-LacZ-treated hearts. Our data indicated that both Ad-VEGF and Ad-LacZ increased arteriolar densities. However, the former increased arterial densities but the latter did not. Compared with the vehicle control, Ad-LacZ reversed occlusion-induced wall thinning and functional impairment but Ad-VEGF did not. Quantitative proteomic analysis showed increased ratios of plasma proteins (such as albumin) and oxygen carriers (such as myoglobin) by Ad-VEGF and decreased ratios of proteins involved in glycolysis, calcium homeostasis and lipolysis by Ad-VEGF. Taken together, our functional, morphological and proteomic data suggest that intramuscular delivery of Ad-LacZ at higher doses may improve ventricular function and wall thinning with arteriolar formation. Excessive amounts of VEGF by Ad-VEGF may offset Ad-LacZ-induced improvement in ventricular functions by interfering with calcium homeostasis and lipolysis in infarcted hearts.
Sung
Ruey-Jen
RJ
Department of Internal Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Chen
Shu-Hui
SH
Luo
Chwan-Yan
CY
Wang
Jieh-Neng
JN
Wu
Chao-Liang
CL
Chen
Yun-Hsiang
YH
Su
Rey-Jyh
RJ
Li
Huey-Jiun
HJ
Tsai
Mei-Ling
ML
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D003331:Coronary Vessels / Q000254:growth & development*; D005822:Genetic Vectors; D006321:Heart / Q000503:physiopathology*; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D019076:Transgenes; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000502:physiology*; D016276:Ventricular Function / Q000502:physiology*
D042442:Vascular Endothelial Growth Factors