Application of bFGF and BDNF to improve angiogenesis and cardiac function.
BACKGROUND
Brain-derived neurotrophic factor (BDNF) is a survival factor for endothelial cells and expresses in the ischemic myocytes. The purpose of this study was to assess whether the simultaneous application of basic fibroblast growth factor (bFGF) and BDNF incorporating gelatin hydrogels improves angiogenesis and cardiac function in ischemic myocardium compared with bFGF applied alone.


METHODS
Direct intramyocardial injection of 100 microg of bFGF plus 25 microg of BDNF, 100 microg of bFGF, or saline were performed in canine infarct model. Colored microspheres were injected to assess the regional myocardial blood flow. Cardiac function was evaluated by cine magnetic resonance imaging (MRI). Immunohistochemical staining and enzyme linked immunosorbent assay (ELISA) were used to observe the localization and expression of bFGF and BDNF protein, and myocardial microvessel density was assessed by von Willebrand factor staining.


RESULTS
Left ventricular ejection fraction (LVEF) was higher in bFGF plus BDNF group than in saline or bFGF group. Blood flow of the peri-infarct region was increased by bFGF plus BDNF treatment. The distribution of bFGF and BDNF-positive cardiomyocytes was similar in three groups. The expression of bFGF and BDNF protein and microvessel density in bFGF plus BDNF group was higher than in the other two groups.


CONCLUSIONS
This study indicates that the sustained dual release of bFGF and BDNF incorporating gelatin hydrogels can improve angiogenesis and left ventricular function in the ischemic myocardium compared with bFGF applied alone. bFGF plus BDNF administration may be a promising therapeutic strategy for the treatment of ischemic myocardium.
Liu
Ying
Y
Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Sun
Lijun
L
Huan
Yi
Y
Zhao
Haitao
H
Deng
Jinglan
J
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000493:pharmacokinetics / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000493:pharmacokinetics / Q000494:pharmacology*; D020100:Hydrogels / Q000494:pharmacology; D007150:Immunohistochemistry; D008833:Microcirculation / Q000187:drug effects; D008863:Microspheres; D017202:Myocardial Ischemia / Q000188:drug therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D013318:Stroke Volume / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy*
D019208:Brain-Derived Neurotrophic Factor; D020100:Hydrogels; D016222:Fibroblast Growth Factor 2