Wang Zhouguang, Long Daniel W, Huang Yan, Khor Sinan, Li Xiaokun, Jian Xiao, Wang Yadong
Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States.
School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China.
ACS Biomater Sci Eng. 2017 Sep 11;3(9):1988-1999. doi: 10.1021/acsbiomaterials.6b00509. Epub 2017 Apr 5.
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.
新出现的证据支持成纤维细胞生长因子-1（FGF1）对心脏病的有益作用，但其应用受到游离蛋白半衰期短和生物活性有限的阻碍。我们设计了一种可注射的凝聚层来促进强大的生长因子递送，这既能保护生长因子又能提高其生物活性。在本研究中，在小鼠中建立了急性心肌梗死模型，并研究了FGF1凝聚层的心脏保护作用。超声心动图结果显示，在实验的6周期间内，FGF1凝聚层比游离FGF1和生理盐水对照组更能抑制心室扩张并保留心脏收缩性。组织学检查显示，FGF1凝聚层可减轻心肌梗死后的炎症和纤维化，显著增加内皮细胞和平滑肌细胞的增殖，并形成稳定的小动脉和毛细血管。此外，FGF1凝聚层可改善心肌梗死后6周心脏干细胞的增殖。然而，相同剂量的游离FGF1与生理盐水治疗相比没有显著差异。因此，单次注射FGF1凝聚层就足以减轻心肌梗死造成的损伤，其结果明显优于同等剂量游离FGF1的结果。
