Fibroblast Growth Factor-1 Released from a Heparin Coacervate Improves Cardiac Function in a Mouse Myocardial...

Emerging evidence supports the beneficial effect of fibroblast growth factor-1 (FGF1) on heart diseases, but its application has been hindered by the short half-life and limited bioactivity of the free protein. We designed an injectable coacervate to facilitate robust growth factor delivery, which would both protect and increase the bioactivity of growth factors. In this study, a model for acute myocardial infarction was established in mice, and the cardioprotective effect of the FGF1 coacervate was investigated. Echocardiographic results showed that the FGF1 coacervate inhibited ventricular dilation and preserved cardiac contractibility more than the free FGF1 and the saline control within the 6-week duration of the experiments. Histological examination revealed that the FGF1 coacervate reduced inflammation and fibrosis post-MI, significantly increased the proliferation of endothelial and mural cells, and resulted in stable arterioles and capillaries. Furthermore, the FGF1 coacervate improved the proliferation of cardiac stem cells 6 weeks post-MI. However, free FGF1, dosed identically, did not show significant difference from saline treatment. Thus, one injection of FGF1 coacervate was sufficient to attenuate the injury caused by MI, and the results were significantly better than those obtained from an equal dose of free FGF1.