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. Materials and methods. Direct intramyocardial injection of 100 mu g of bFGF plus 25 mu g of BDNF, 100 tag 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. (c) 2006 Elsevier Inc. All rights reserved.