Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Department of Cardiology and Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
ACS Appl Mater Interfaces. 2021 May 19;13(19):22131-22141. doi: 10.1021/acsami.0c23153. Epub 2021 May 6.
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 (Comp., Nap-FFEG-IVGGYPWWMDV), which can strongly activate the pro-HGF and initiate HGF-Met signaling. Studies have proven that Comp. possesses a better ability to activate the pro-HGF to perform antiapoptosis and pro-angiogenesis. results have confirmed that the retention time of Comp. and its accumulation in the infarct area of the heart are promoted. Moreover, Comp. 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.
血液灌注重建是拯救和保护急性心肌梗死（AMI）后心脏功能的关键治疗方法。肝细胞生长因子前体（pro-HGF）的激活对促进血管生成和抗细胞凋亡有显著作用。AMI 引起的氧/葡萄糖剥夺（OGD）可诱导血管外膜成纤维细胞分化为肌成纤维细胞并分泌 pro-HGF。同时，AMI 期间内皮细胞中肝细胞生长因子（HGF）的特定 Met 受体上调。然而，AMI 的预后不佳表明 pro-HGF 没有被有效激活。提高 pro-HGF 的激活效率可能对 AMI 的治疗发挥积极作用。在此，我们设计了由化合物（Comp.，Nap-FFEG-IVGGYPWWMDV）自组装而成的超分子纳米纤维，可强烈激活 pro-HGF 并启动 HGF-Met 信号通路。研究证明，Comp. 具有更强的激活 pro-HGF 以发挥抗凋亡和促血管生成作用。研究结果证实，Comp. 的保留时间及其在心脏梗死区的积累得到了促进。此外，Comp. 还能有效促进 AMI 边缘区的血管生成，减少心肌纤维化，保护心脏功能。在此，我们将通过超分子自组装优化生物活性肽的结构，并通过提高其效率来放大其治疗效果，为 AMI 的治疗提供新策略。
