Qishen Granule protects against myocardial ischemia by promoting angiogenesis through BMP2-Dll4-Notch1 pathway

芪参颗粒通过BMP2-Dll4-Notch1通路促进血管生成防治心肌缺血

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作者:Yiqin Hong, Hui Wang, Hanyan Xie, Xinyi Zhong, Xu Chen, Lishuang Yu, Yawen Zhang, Jingmei Zhang, Qiyan Wang, Binghua Tang, Linghui Lu, Dongqing Guo

Conclusion

QSG protected against MI by promoting angiogenesis through BMP2-Dll4-Notch1 pathway. BMP2 might be a promising therapeutic target for IHD.

Methods

In vivo study was conducted on rat model of myocardial infarction. QSG was performed daily at a dose of 2.352 g/kg for four weeks. Cardiac function was assessed by echocardiogram and pro-angiogenic effects were evaluated by Laser Doppler and CD31 expression. Oxygen-glucose deprivation (OGD) was applied in cultured human umbilical vein endothelial cells (HUVECs). Cell viability, wound healing and tube formation assay were used to test functions of HUVECs. ELISA and Western blots were used to assess protein expressions of bone morphogenetic protein 2-delta-like 4-notch homolog 1 (BMP2-Dll4-Notch1) signaling pathway.

Objective

Therapeutic angiogenesis has become a promising approach for treating ischemic heart disease (IHD). The present study aims to investigate the effects of Qishen Granule (QSG) on angiogenesis in myocardial ischemia (MI) and the potential mechanism.

Results

The results showed that QSG improved heart function, cardiac blood flow and microvessel density in myocardial ischemic rats. In vitro, QSG protected HUVECs by promoting the cell viability and tube formation. QSG upregulated bone morphogenetic protein-2 (BMP2) and downregulated delta-like 4 (Dll4) and notch homolog 1 (Notch1) expressions both in rats and HUVECs.

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