Myocardial protection by heparin-based coacervate of FGF10
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 b...
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KeAi Communications Co., Ltd.
2021-07-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X20303224 |
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| author | Zhouguang Wang Yan Huang Yan He Sinan Khor Xingxing Zhong Jian Xiao Qingsong Ye Xiaokun Li |
| author_facet | Zhouguang Wang Yan Huang Yan He Sinan Khor Xingxing Zhong Jian Xiao Qingsong Ye Xiaokun Li |
| author_sort | Zhouguang Wang |
| collection | DOAJ |
| description | 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. |
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| language | English |
| last_indexed | 2024-04-24T08:13:30Z |
| publishDate | 2021-07-01 |
| publisher | KeAi Communications Co., Ltd. |
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| series | Bioactive Materials |
| spelling | doaj.art-084bc0d6097449758396506a2a7a3df12024-04-17T04:34:35ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2021-07-016718671877Myocardial protection by heparin-based coacervate of FGF10Zhouguang Wang0Yan Huang1Yan He2Sinan Khor3Xingxing Zhong4Jian Xiao5Qingsong Ye6Xiaokun Li7School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035, China; Engineering Laboratory of Zhejiang Province for Pharmaceutical Development of Growth Factors, Biomedical Collaborative Innovation Center of Wenzhou, Wenzhou, Zhejiang, 325035, China; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, USASchool of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035, China; Engineering Laboratory of Zhejiang Province for Pharmaceutical Development of Growth Factors, Biomedical Collaborative Innovation Center of Wenzhou, Wenzhou, Zhejiang, 325035, ChinaLaboratory of Regenerative Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, 430064, ChinaDepartment of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, USADepartment of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, USASchool of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035, China; Engineering Laboratory of Zhejiang Province for Pharmaceutical Development of Growth Factors, Biomedical Collaborative Innovation Center of Wenzhou, Wenzhou, Zhejiang, 325035, ChinaCentre of Regenerative Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China; School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 325035, China; Corresponding author. Centre of Regenerative Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China.School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035, China; Engineering Laboratory of Zhejiang Province for Pharmaceutical Development of Growth Factors, Biomedical Collaborative Innovation Center of Wenzhou, Wenzhou, Zhejiang, 325035, China; Research Units of Clinical Translation of Cell Growth Factors and Diseases Research, Chinese Academy of Medical Science, China; Corresponding author. School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035, China.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.http://www.sciencedirect.com/science/article/pii/S2452199X20303224Fibroblast growth factor-10AngiogenesisControlled releaseMyocardial infarctionCoacervate |
| spellingShingle | Zhouguang Wang Yan Huang Yan He Sinan Khor Xingxing Zhong Jian Xiao Qingsong Ye Xiaokun Li Myocardial protection by heparin-based coacervate of FGF10 Bioactive Materials Fibroblast growth factor-10 Angiogenesis Controlled release Myocardial infarction Coacervate |
| title | Myocardial protection by heparin-based coacervate of FGF10 |
| title_full | Myocardial protection by heparin-based coacervate of FGF10 |
| title_fullStr | Myocardial protection by heparin-based coacervate of FGF10 |
| title_full_unstemmed | Myocardial protection by heparin-based coacervate of FGF10 |
| title_short | Myocardial protection by heparin-based coacervate of FGF10 |
| title_sort | myocardial protection by heparin based coacervate of fgf10 |
| topic | Fibroblast growth factor-10 Angiogenesis Controlled release Myocardial infarction Coacervate |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X20303224 |
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