Supramolecular Self-Assembled Nanofibers Efficiently Activate the Precursor of Hepatocyte Growth Factor for Angiogenesis in Myocardial Infarction Therapy
Supramolecular Self-Assembled Nanofibers Efficiently Activate the Precursor of Hepatocyte Growth Factor for Angiogenesis in Myocardial Infarction Therapy
复制标题
超分子自组装纳米纤维有效激活肝细胞生长因子前体促进心肌梗塞治疗中的血管生成
DOI：
10.1021/acsami.0c23153
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发表时间：
2021-05-07
影响因子：
9.5
通讯作者：
Chen, Minsheng
中科院分区：
文献类型：
--
作者：
Guo, Wenjie;Feng, Weijing;Chen, Minsheng
急性心肌梗死（AMI）后血液灌注的重建是挽救和保护心功能的重要治疗手段。肝细胞生长因子前体（pro-HGF）的激活在促进血管生成和抗凋亡方面具有显著作用。急性心肌梗死（AMI）引起的氧/糖剥夺（OGD）可诱导血管外膜成纤维细胞向肌成纤维细胞分化，并分泌促肝细胞生长素原（pro-HGF）。同时，在AMI期间，肝细胞生长因子（HGF）的特异性Met受体在内皮细胞中上调。然而，AMI的预后差表明pro-HGF未被有效激活。提高促肝细胞生长因子原的活化效率可能对AMI的治疗有积极作用。在此，我们设计了由化合物1（Comp.1，Nap-FFEG-IVGGYPWWMDV）自组装的超分子纳米纤维，其可以强烈激活pro-HGF并启动HGF-Met信号传导。研究证明，化合物1具有更好的激活促肝细胞生长因子（pro-HGF）的能力，从而发挥抗凋亡和促血管生成的作用。体内结果已经证实，化合物1的保留时间及其在心脏梗塞区域中的积累得到促进。此外，化合物1在促进AMI边缘区域的血管生成、减少心肌纤维化和保护心脏功能方面发挥有效作用。本研究旨在通过超分子自组装技术优化活性肽的结构，提高活性肽的效率，增强其治疗效果，为AMI的治疗提供新的策略。
The reconstruction of blood perfusion is a crucial therapeutic method to save and protect cardiac function after acute myocardial infarction (AMI). The activation of the hepatocyte growth factor precursor (pro-HGF) has a significant effect on promoting angiogenesis and antiapoptosis. The oxygen/glucose deprivation (OGD) caused by AMI could induce vascular adventitia fibroblasts to differentiate into myofibroblasts and secrete the pro-HGF. Meanwhile, the specific Met receptor of the hepatocyte growth factor (HGF) is upregulated in endothelial cells during AMI. However, the poor prognosis of AMI suggests that the pro-HGF is not effectively activated. Improving the activation efficiency of the pro-HGF may play a positive role in the treatment of AMI. Herein, we designed supramolecular nanofibers self-assembled by compound 1 (Comp.1, Nap-FFEG-IVGGYPWWMDV), which can strongly activate the pro-HGF and initiate HGF-Met signaling. Studies have proven that Comp.1 possesses a better ability to activate the pro-HGF to perform antiapoptosis and pro-angiogenesis. In vivo results have confirmed that the retention time of Comp.1 and its accumulation in the infarct area of the heart are promoted. Moreover, Comp.1 plays an effective role in promoting angiogenesis in the marginal area of AMI, reducing myocardial fibrosis, and protecting cardiac function. Herein, we will optimize the structure of bioactive peptides through supramolecular self-assembly and amplify their therapeutic effect by improving their efficiency, providing a new strategy for the therapy of AMI.