Myocardial protection by heparin-based coacervate of FGF10  

作　　者：Zhouguang Wang Yan Huang Yan He Sinan Khor Xingxing Zhong Jian Xiao Qingsong Ye Xiaokun Li 

机构地区：[1]School of Pharmacy,Key Laboratory of Biotechnology and Pharmaceutical Engineering,Wenzhou Medical University,Wenzhou,325035,China [2]Engineering Laboratory of Zhejiang Province for Pharmaceutical Development of Growth Factors,Biomedical Collaborative Innovation Center of Wenzhou,Wenzhou,Zhejiang,325035,China [3]Department of Molecular Pharmacology,Albert Einstein College of Medicine,Bronx,NY,10461,USA [4]Laboratory of Regenerative Medicine,Tianyou Hospital,Wuhan University of Science and Technology,Wuhan,430064,China [5]Centre of Regenerative Medicine,Renmin Hospital of Wuhan University,Wuhan,430060,China [6]Research Units of Clinical Translation of Cell Growth Factors and Diseases Research,Chinese Academy of Medical Science,China [7]School and Hospital of Stomatology,Wenzhou Medical University,Wenzhou,325035,China

出　　处：《Bioactive Materials》2021年第7期1867-1877,共11页生物活性材料（英文）

基　　金：This work was supported by grants from Advanced Postdoctoral Programs of Zhejiang(zj2019030);China Postdoctoral Science Foundation(2019M662015);Research Unit of Research and Clinical Translation of Cell Growth Factors and Diseases,Chinese Academy of Medical Science(No.2019RU010 to X.L.);CAMS Innovation Fund for Medical Sciences(2019-I2M-5-028),China.

摘　　要：Heart disease is still the leading killer all around the world,and its incidence is expected to increase over the next decade.Previous reports have already shown the role of fibroblast growth factor10(FGF10)in alleviating heart diseases.However,FGF10 has not been used to treat heart diseases because the free protein has short half-life and low bioactivity.Here,an injectable coacervate was designed to protect growth factor from degradation during delivery and the effects of the FGF10 coacervate were studied using a mice acute myocardial infarction(MI)model.As shown in our echocardiographic results,a single injection of FGF10 coacervate effectively inhibited preserved cardiac contractibility and ventricular dilation when compared with free FGF10 and the saline treatment 6 weeks after MI.It is revealed in histological results that the MI induced myocardial inflammation and fibrosis was reduced after FGF10 coacervate treatment.Furthermore,FGF10 coacervate treatment could improve arterioles and capillaries stabilization through increasing the proliferation of endothelial and mural cells.However,with the same dosage,no statistically significant difference was shown between free FGF10,heparin+FGF10 and saline treatment,especially in long term.On another hand,FGF10 coacervate also increased the expression of cardiac-associated the mRNA(cTnT,Cx43 and α-SMA),angiogenic factors(Ang-1 and VEGFA)and decreased the level of inflammatory factor(tumor necrosis factor-α).The downstream signaling of the FGF10 was also investigated,with the western blot results showing that FGF10 coacervate activated the p-FGFR,PI3K/Akt and ERK1/2 pathways to a more proper level than free FGF10 or heparin+FGF10.In general,it is revealed in this research that one-time injection of FGF10 coacervate sufficiently attenuated MI induced injury when compared with an equal dose of free FGF10 or heparin+FGF10 injection.

关 键 词：Fibroblast growth factor-10 ANGIOGENESIS Controlled release Myocardial infarction COACERVATE 

分 类 号：R542.2[医药卫生—心血管疾病]