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Myocardial protection by heparin-based coacervate of FGF10

Bioactive Materials 2021年第7期6卷 1867-1877页

作者： Zhouguang Wang Yan Huang Yan He Sinan Khor Xingxing Zhong Jian Xiao Qingsong Ye Xiaokun Li School of Pharmacy Key Laboratory of Biotechnology and Pharmaceutical EngineeringWenzhou Medical UniversityWenzhou325035China Engineering Laboratory of Zhejiang Province for Pharmaceutical Development of growth factors Biomedical Collaborative Innovation Center of WenzhouWenzhouZhejiang325035China Department of Molecular Pharmacology Albert Einstein College of MedicineBronxNY10461USA Laboratory of Regenerative Medicine Tianyou HospitalWuhan University of Science and TechnologyWuhan430064China Centre of Regenerative Medicine Renmin Hospital of Wuhan UniversityWuhan430060China Research Units of Clinical Translation of Cell growth factors and Diseases Research Chinese Academy of Medical ScienceChina School and Hospital of Stomatology Wenzhou Medical UniversityWenzhou325035China

Heart disease is still the leading killer all around the world,and its incidence is expected to increase over the next *** reports have already shown the role of fibroblast growth factor10(FGF10)in alleviating heart ***,FGF10 has not been used to treat heart diseases because the free protein has short half-life and low ***,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)*** 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 *** is revealed in histological results that the MI induced myocardial inflammation and fibrosis was reduced after FGF10 coacervate ***,FGF10 coacervate treatment could improve arterioles and capillaries stabilization through increasing the proliferation of endothelial and mural ***,with the same dosage,no statistically significant difference was shown between free FGF10,heparin+FGF10 and saline treatment,especially in long *** 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+*** 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

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