Astragalus propinquus schischkin and Salvia miltiorrhiza bunge promote angiogenesis to treat myocardial ischemia via Ang-1/Tie-2/FAK pathway.
Astragalus propinquus schischkin and Salvia miltiorrhiza bunge promote angiogenesis to treat myocardial ischemia via Ang-1/Tie-2/FAK pathway.
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DOI：
10.3389/fphar.2022.1103557
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发表时间：
2022
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
黄芪和丹参是临床上常用的治疗心肌缺血的药物。然而，AS对MI的影响及其机制尚未完全清楚。在这里，我们探讨了它们联合使用的心脏保护作用，以及通过周细胞募集促进血管生成的机制。我们的数据表明，AS减少MI和保护心脏功能。AS治疗的MI小鼠表现出ST段位移和复极时间减少，射血分数增加，BNP和NT-proBNP表达减少。病理学研究表明，AS可缩小心肌梗死面积，减缓心肌重构和纤维化进程。此外，AS还可增加血小板源性生长因子受体β（PDGFR-β）、血小板内皮细胞粘附分子-1（CD 31）以及血管内皮钙粘蛋白（VE-cadherin）、血管内皮生长因子（VEGF）和转化生长因子β（TGF-β）等血管生成相关蛋白的含量。此外，这些植物药还上调了血管生成素-1（Ang-1）、磷酸化血管生成素-1受体（p-Tie-2）、粘着斑激酶（FAK）和生长因子受体结合蛋白7（GRB 7）的表达，提示其心肌保护相关的血管生成作用与周细胞募集有关，可能通过Ang-1/Tie-2/FAK途径实现。综上所述，AS通过保护心功能、减轻心脏病理改变、阻止心力衰竭的进展来治疗MI，这与周细胞募集后的血管生成有关。因此，一定剂量的AS是一种很有前途的心肌梗死治疗药物，具有广阔的应用前景。
Astragalus propinquus Schischkin and Salvia miltiorrhiza Bunge (AS) have been clinically used as adjunctive drugs in the treatment of myocardial ischemia (MI). However, the effect and mechanism of AS on MI have yet to be fully recognized. Here, we explored the cardioprotective effect of their combined use, and the mechanism of promoting angiogenesis through pericyte recruitment. Our data revealed that AS reduced MI and protects cardiac function. AS-treated MI mice exhibited reduced ST-segment displacement and repolarization time, increased ejection fraction, and less BNP and NT-proBNP expression. Pathological studies showed that, AS reduced the area of infarcted myocardium and slowed down the progress of cardiac remodelling and fibrosis. In addition, AS increased the content of platelet-derived growth factor receptors β (PDGFR-β), platelet endothelial cell adhesion molecule-1 (CD31) and angiogenesis-related proteins including vascular endothelial cadherin (VE-cadherin), Vascular Endothelial Growth Factor (VEGF) and transforming growth factor β (TGF-β). Moreover, these botanical drugs upregulated the expression of Angiopoietin-1 (Ang-1), phosphorylated angiopoietin-1 receptor (p-Tie-2), focal adhesion kinase (FAK) and growth factor receptor bound protein 7 (GRB7), indicating that the cardioprotection-related angiogenesis effect was related to pericyte recruitment, which may be through Ang-1/Tie-2/FAK pathway. In summary, AS can treat MI by protecting cardiac function, attenuating cardiac pathological changes, and hindering the progression of heart failure, which is related to angiogenesis after pericyte recruitment. Therefore, AS at a certain dose can be a promising treatment for MI with broad application prospects.
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