Qi-Blood Harmony Formula ameliorates myocardial infarction in coronary atherosclerotic heart disease by reversing circRNA-mediated inhibition of angiogenesis via EIF4A3 stabilization.
Myocardial infarction (MI) is the most severe clinical complication of coronary atherosclerotic heart disease (CHD), representing a leading cause of global morbidity and mortality. Qi-Blood Harmony Formula (QBHF), a traditional Chinese medicine, has shown clinical promise for managing MI; however, its underlying mechanisms remain to be fully elucidated.
This study aimed to explore the therapeutic mechanism of QBHF against MI in the context of CHD, with a specific focus on its role in angiogenesis.
QBHF chemical components were characterized by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Therapeutic efficacy was evaluated in a high-fat diet-fed ApoE-/- mouse model with left anterior descending coronary artery ligation and in a hypoxia-induced endothelial cell model. Cardiac function and angiogenesis were assessed through histological, functional, and molecular assays, with the underlying mechanisms further investigated using bioinformatics and experimental validation.
Chemical profiling identified 67 compounds in QBHF, with eight major constituents quantified. In atherosclerosis-myocardial infarction (AS-MI) mice, QBHF dose-dependently improved cardiac function, attenuated myocardial injury, and upregulated angiogenic markers. In vitro, QBHF enhanced hypoxia-induced proliferation, migration, and tube formation in EA.hy926 cells. Mechanistically, a specific circular RNA (hsa_circ_0003296) was found to be significantly upregulated in the peripheral blood of AS and MI patients. It directly bound to eukaryotic initiation factor 4A-III (EIF4A3) to promote its ubiquitin-mediated degradation. QBHF suppressed hsa_circ_0003296 expression, thereby preventing EIF4A3 degradation. The stabilized EIF4A3 subsequently prolonged the mRNA half-lives of vascular endothelial growth factor A (VEGFA) and VEGF receptor 2 (VEGFR2), thereby promoting angiogenesis.
These results suggest that QBHF ameliorates MI in CHD by reversing hsa_circ_0003296-mediated inhibition of angiogenesis. This process is executed through the stabilization of EIF4A3, which enhances the mRNA stability of VEGFA and VEGFR2.
This study aimed to explore the therapeutic mechanism of QBHF against MI in the context of CHD, with a specific focus on its role in angiogenesis.
QBHF chemical components were characterized by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Therapeutic efficacy was evaluated in a high-fat diet-fed ApoE-/- mouse model with left anterior descending coronary artery ligation and in a hypoxia-induced endothelial cell model. Cardiac function and angiogenesis were assessed through histological, functional, and molecular assays, with the underlying mechanisms further investigated using bioinformatics and experimental validation.
Chemical profiling identified 67 compounds in QBHF, with eight major constituents quantified. In atherosclerosis-myocardial infarction (AS-MI) mice, QBHF dose-dependently improved cardiac function, attenuated myocardial injury, and upregulated angiogenic markers. In vitro, QBHF enhanced hypoxia-induced proliferation, migration, and tube formation in EA.hy926 cells. Mechanistically, a specific circular RNA (hsa_circ_0003296) was found to be significantly upregulated in the peripheral blood of AS and MI patients. It directly bound to eukaryotic initiation factor 4A-III (EIF4A3) to promote its ubiquitin-mediated degradation. QBHF suppressed hsa_circ_0003296 expression, thereby preventing EIF4A3 degradation. The stabilized EIF4A3 subsequently prolonged the mRNA half-lives of vascular endothelial growth factor A (VEGFA) and VEGF receptor 2 (VEGFR2), thereby promoting angiogenesis.
These results suggest that QBHF ameliorates MI in CHD by reversing hsa_circ_0003296-mediated inhibition of angiogenesis. This process is executed through the stabilization of EIF4A3, which enhances the mRNA stability of VEGFA and VEGFR2.
Authors
Huang Huang, Guo Guo, Chen Chen, Xin Xin, Xie Xie, Hu Hu, Miao Miao, Ma Ma, Ma Ma, Zhu Zhu, Yuan Yuan, Cong Cong
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