MMP 9-instructed assembly of bFGF nanofibers in ischemic myocardium to promote heart repair.
MMP 9-instructed assembly of bFGF nanofibers in ischemic myocardium to promote heart repair.
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DOI：
10.7150/thno.77345
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发表时间：
2022
期刊：
影响因子：
12.4
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Wang Y;Wang D;Wu C;Wang B;He S;Wang H;Liang G;Zhang Y
背景资料：心肌梗死（MI）的唯一有效治疗方法是及时恢复梗死区的冠状动脉血流，但进一步再灌注会加重心肌损伤并导致远端冠状动脉无复流，影响患者预后。血管新生可能是心肌梗死后重建血供挽救缺血心肌的重要治疗策略。碱性成纤维细胞生长因子（bFGF）已被证明可以促进血管生成。然而，直接静脉内施用bFGF不是可行的选择，因为其在体内的半衰期差。研究方法：本论文以碱性成纤维细胞生长因子（bFGF）为载体，构建了一种新型的肽段Lys-Lys-Pro-Leu-Gly-Leu-Ala-Gly-Phe-Phe（K2），将bFGF包裹于K2胶束中形成bFGF@K2胶束。结果：bFGF@K2胶束对大鼠心肌缺血再灌注（MI/R）模型的保护作用强于游离bFGF。体外实验结果表明，bFGF@K2胶束可被基质金属肽酶9（MMP-9）裂解，通过两亲性变化产生bFGF@Nanofiber。体内实验表明，静脉注射bFGF@K2胶束可使其重组为bFGF@Nanofiber，并通过MMP-9的高表达和组装诱导滞留效应（AIR）使bFGF在大鼠缺血心肌中长期滞留。MI/R模型建立后28 d，bFGF@K2胶束治疗组大鼠心肌纤维化明显减轻，心功能明显改善。结论：我们预测，我们的策略可以应用于未来的MI治疗的临床。
Background: The only effective treatment for myocardial infarction (MI) is the timely restoration of coronary blood flow in the infarcted area, but further reperfusion exacerbates myocardial injury and leads to distal coronary no-reflow, which affects patient prognosis. Angiogenesis could be an important therapeutic strategy for re-establishing the blood supply to save the ischemic myocardium after MI. Basic fibroblast growth factor (bFGF) has been shown to promote angiogenesis. However, direct intravenous administration of bFGF is not a viable option given its poor half-life in vivo. Methods: Herein, we developed a peptide Lys-Lys-Pro-Leu-Gly-Leu-Ala-Gly-Phe-Phe (K2) to encapsulate bFGF to form bFGF@K2 micelle and proposed an enzyme-instructed self-assembly (EISA) strategy to deliver and slowly release bFGF in the ischemic myocardium. Results: The bFGF@K2 micelle exerted a stronger cardioprotective effect than free bFGF in a rat model of myocardial ischemia-reperfusion (MI/R). In vitro results revealed that the bFGF@K2 micelle could be cleaved by matrix metallopeptidase 9 (MMP-9) to yield bFGF@Nanofiber through amphipathic changes. In vivo experiments indicated that intravenous administration of bFGF@K2 micelle could lead to their restructuring into bFGF@Nanofiber and long term retention of bFGF in the ischemic myocardium of rat due to high expression of MMP-9 and assembly-induced retention (AIR) effect, respectively. Twenty-eight days after MI/R model establishment, bFGF@K2 micelle treatment significantly reduced fibrosis and improved cardiac function of the rats. Conclusion: We predict that our strategy could be applied in clinic for MI treatment in the future.
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影响因子：
14
作者：
Alves-Sampaio, Alexandra;Garcia-Rama, Concepcion;Collazos-Castro, Jorge E.
通讯作者：
Collazos-Castro, Jorge E.
影响因子：
19
作者：
Li, Zhenhua;Zhu, Dashuai;Wang, Xiaojie
通讯作者：
Wang, Xiaojie
影响因子：
17.1
作者：
Li J;Bullara D;Du X;He H;Sofou S;Kevrekidis IG;Epstein IR;Xu B
通讯作者：
Xu B
DOI：
10.1186/s13054-016-1352-z
发表时间：
2016-07-04
期刊：
Critical care (London, England)
影响因子：
--
作者：
O'Neal JB;Shaw AD;Billings FT 4th
通讯作者：
Billings FT 4th
影响因子：
37.8
作者：
Figueras, Jaume;Alcalde, Oscar;Lidon, Rosa-Maria
通讯作者：
Lidon, Rosa-Maria