Feed

This study investigated the therapeutic effects of the Qixue Bingzhi Formula(QXBZ) on coronary heart disease, focusing on its bidirectional regulation of angiogenesis in myocardial ischemia and atherosclerosis, using in vivo and in vitro models. Male ApoE~(-/-)mice were fed a high-fat diet for 9 weeks and then randomized into the following groups, with high-fat feeding continuing until 12 weeks: a control group, a model group, QXBZ groups(at high, medium, and low doses of 11.7, 5.85, and 2.92 g·kg~(-1)·d~(-1), respectively), and a positive group(receiving 26 mg·kg~(-1)·d~(-1) metoprolol plus 5.2 mg·kg~(-1)·d~(-1) simvastatin), with 12 mice per group. A myocardial infarction and atherosclerosis(MI-AS) composite model was established by ligating the left anterior descending coronary artery at week 11, and drug administration continued for 2 weeks post-surgery. C57BL/6J mice served as a blank control, receiving standard diet and intragastric administration of normal saline throughout the study and being subjected to threading but not ligating the coronary artery. After the final administration, cardiac function and carotid artery intima-media thickness were assessed by ultrasound. Histopathological examinations of the heart and plaques were performed using hematoxylin and eosin(HE), Masson, and Movat staining, along with immunofluorescence. Blood lipid levels were measured using biochemical assays, and the expression level of vascular endothelial growth factor A(VEGFA) was determined by RT-qPCR and Western blot. In vitro, endothelial cells were used to establish a hypoxic-induced(1% O_2) MI model and an oxidized low-density lipoprotein(ox-LDL)-induced AS model and divided into control, model, QXBZ(2.5%, 5%, 10%, and 15%), and positive groups. Cell proliferation was assessed using the cell counting kit-8(CCK-8) assay, cell migration was evaluated by the scratch assay, and tube formation ability was examined by the tube formation assay. The expression level of VEGFA was detected by RT-qPCR and Western blot. RESULTS:: showed that QXBZ significantly reduced triglyceride and low-density lipoprotein cholesterol levels, increased left ventricular ejection fraction and left ventricular fractional shortening, and attenuated both myocardial fibrosis area and atherosclerotic plaque area in MI-AS composite model mice. It enhanced the fluorescence intensities of cluster of differentiation 31(CD31) and α-smooth muscle actin(α-SMA) in the ischemic myocardium but decreased them in plaques. QXBZ also promoted cell viability, migration, and tube formation in the MI model, while inhibiting these processes in the AS model. Furthermore, QXBZ upregulated VEGFA expression in the ischemic myocardium and the MI cell model, but downregulated it in the aortic tissue and the AS cell model, demonstrating a microenvironment-dependent bidirectional regulation. These findings suggested that QXBZ ameliorates coronary heart disease by promoting angiogenesis in the ischemic myocardium while inhibiting angiogenesis in plaques, potentially through bidirectional regulation of the VEGFA signaling pathway in different pathological microenvironments of ischemic myocardium and plaques.