医学
肝细胞生长因子
血管生成
生长因子
血管内皮生长因子
成纤维细胞生长因子
碱性成纤维细胞生长因子
治疗性血管生成
动脉发生
心力衰竭
新生血管
纤维化
内科学
内分泌学
癌症研究
受体
血管内皮生长因子受体
作者
Sébastien Banquet,Elodie Gomez,Lionel Nicol,Florence Edwards-Levy,Jean-Paul Henry,Renhai Cao,Damien Schapman,Brigitte Dautreaux,Françoise Lallemand,Fabrice Bauer,Yihai Cao,Christian Thuillez,Paul G.H. Mulder,Vincent Richard,Ebba Brakenhielm
出处
期刊:Circulation
[Ovid Technologies (Wolters Kluwer)]
日期:2011-08-30
卷期号:124 (9): 1059-1069
被引量:75
标识
DOI:10.1161/circulationaha.110.010264
摘要
Background— Therapeutic angiogenesis is a promising approach for the treatment of cardiovascular diseases, including myocardial infarction and chronic heart failure. We aimed to improve proangiogenic therapies by identifying novel arteriogenic growth factor combinations, developing injectable delivery systems for spatiotemporally controlled growth factor release, and evaluating functional consequences of targeted intramyocardial growth factor delivery in chronic heart failure. Methods and Results— First, we observed that fibroblast growth factor and hepatocyte growth factor synergistically stimulate vascular cell migration and proliferation in vitro. Using 2 in vivo angiogenesis assays (n=5 mice per group), we found that the growth factor combination results in a more potent and durable angiogenic response than either growth factor used alone. Furthermore, we determined that the molecular mechanisms involve potentiation of Akt and mitogen-activated protein kinase signal transduction pathways, as well as upregulation of angiogenic growth factor receptors. Next, we developed crosslinked albumin-alginate microcapsules that sequentially release fibroblast growth factor-2 and hepatocyte growth factor. Finally, in a rat model of chronic heart failure induced by coronary ligation (n=14 to 15 rats per group), we found that intramyocardial slow release of fibroblast growth factor-2 with hepatocyte growth factor potently stimulates angiogenesis and arteriogenesis and prevents cardiac hypertrophy and fibrosis, as determined by immunohistochemistry, leading to improved cardiac perfusion after 3 months, as shown by magnetic resonance imaging. These multiple beneficial effects resulted in reduced adverse cardiac remodeling and improved left ventricular function, as revealed by echocardiography. Conclusion— Our data showing the selective advantage of using fibroblast growth factor-2 together with hepatocyte growth factor suggest that this growth factor combination may constitute an efficient novel treatment for chronic heart failure.
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