Transcription factor Foxp1 stimulates angiogenesis in adult rat after myocardial infarction

Abstract Background: Coronary heart disease is the leading cause of death and major socioeconomic burden worldwide. The ischemia and hypoxia caused by the sudden occlusion of the main coronary arteries lead to myocardial infarction, leading to hypertrophic growth of cardiomyocytes and left ventricular dilatation, which eventually develops into heart failure. Timely and effective revascularization is extremely important for saving the infarcted myocardium and improving heart function.Purpose: To explore the effect of transcription factor Foxp1 on angiogenesis after myocardial infarction from two levels of in vivo and in vitro experiments.Methods: The myocardial infarction model was established in male SD rats to detect FoxP1 expression; lentivirus carrying FoxP1 interfering RNA was injected by multi-point method for 4 weeks, and tissue immunofluorescence and immunohistochemical experiments were performed to observe myocardial endothelial cell proliferation and collagen deposition. Human umbilical vein endothelial cells (HUVEC) were cultured in a hypoxic cell incubator to detect the expression changes of FoxP1 transcription level and protein level at different time points; Lentiviruses carrying specific FoxP1 gene interfering RNAs were used to transfect HUVECs, and cells were used for transfection. Immunofluorescence and flow cytometry were used to detect the proliferation ability of HUVEC in different groups; meanwhile, cell scratch assay was used to detect the migration ability of HUVEC of different groups and tubule formation experiment to observe the tube formation ability.Results: The myocardial infarction rat model was successfully established. Compared with the sham-operated group, immunofluorescence experiments showed that the expression of FoxP1 was significantly increased. After the lentivirus of FoxP1 interfering RNA was injected into myocardial infarction rats, the expression of FoxP1 decreased, endothelial cell proliferation decreased, and collagen deposition increased. Angiogenesis is reduced. When HUVECs were treated in a 5% hypoxia incubator, it was found that the expression of FoxP1 in endothelial cells increased within 24 hours. After transfection of HUVECs with FoxP1 interfering RNA lentivirus, their proliferation, migration and tube formation abilities decreased significantly.Conclusions: Hypoxia can promote the expression level of endothelial cells FoxP1 to a certain extent; foxp1 may promote the formation of new blood vessels in the infarct area by promoting endothelial cell proliferation and inhibiting endothelial cell apoptosis after myocardial infarction. FoxP1 may provide a promising therapeutic target by promoting effective angiogenesis in the treatment of myocardial infarction.