Hypoxia-Inducible Factor 1 alpha (HIF-1α)/Vascular Endothelial Growth Factor (VEGF) Pathway Participates in Angiogenesis of Myocardial Infarction in Muscone-Treated Mice: Preliminary Study
Yingqiang Du, Yingbin Ge, Zhihui Xu, Nan Aa, Xin Gu, Haoyu Meng, Zhou Lin, Dongxiao Zhu, Jingjing Shi, Ruijuan Zhuang, Xueming Wu, Xiaoyan Wang, Zhijian Yang
(Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (mainland))
Med Sci Monit 2018; 24:8870-8877
Angiogenesis plays a crucial role in myocardial infarction (MI) treatment by ameliorating myocardial remodeling, thus improving cardiac function and preventing heart failure. Muscone has been reported to have beneficial effects on cardiac remodeling in MI mice. However, the effects of muscone on angiogenesis in MI mice and its underlying mechanisms remain unknown.
MATERIAL AND METHODS: Mice were randomly divided into sham, MI, and MI+muscone groups. The MI mouse model was established by ligating the left anterior descending coronary artery. Mice in the sham group received the same procedure except for ligation. Mice were administered muscone or an equivalent volume of saline for 4 consecutive weeks. Cardiac function was evaluated by echocardiograph after MI for 2 and 4 weeks. Four weeks later, all mice were sacrificed and Masson’s trichrome staining was used to assess myocardial fibrosis. Isolectin B4 staining was applied to evaluate the angiogenesis in mouse hearts. Immunohistochemistry, Western blot analysis, and quantitative real-time polymerase chain reaction (qPCR) were performed to analyze expression levels of HIF-1a and its downstream genes.
RESULTS: Compared with the MI group, muscone treatment significantly improved cardiac function and reduced myocardial fibrosis. Moreover, muscone enhanced angiogenesis in the peri-infarct region and p-VEGFR2 expression in the vascular endothelial cells. Western blot analysis and qPCR showed that muscone upregulated expression levels of HIF-1a and VEGFA.
CONCLUSIONS: Muscone improved cardiac function in MI mice through augmented angiogenesis. The potential mechanism of muscone treatment in regulating angiogenesis of MI mice was upregulating expression levels of HIF-1α and VEGFA.
Keywords: Angiogenesis Inducing Agents, Hypoxia-Inducible Factor 1, alpha Subunit, Myocardial Infarction, Vascular Endothelial Growth Factor A