Influence of the interaction between the Notch signaling pathway and Toll-like receptor 4 on the function of CD14+ monocytes in patients with coronary heart disease

Objective To investigate the influence of the interaction between the Notch signaling pathway and Toll like receptor 4 (TLR4) on the function of CD14+ monocytes in patients with coronary heart disease. Methods A total of 101 patients with coronary heart disease who were admitted to our hospital from April 2019 to August 2020 were enrolled, and according to their disease conditions, they were divided into stable angina pectoris (SAP) group, unstable angina pectoris (UAP) group, and acute myocardial infarction (AMI) group; meanwhile, 40 individuals who underwent physical examination during the same period of time were enrolled as control group. Fasting peripheral venous blood samples were collected from each group of subjects, and mononuclear cells were isolated. RT-qPCR was used to measure the mRNA expression levels of Notch1, Notch2, and TLR1-10 in mononuclear cells. Magnetic-activated cell sorting was performed to isolate CD14+ monocytes from peripheral blood mononuclear cells for the three groups of patients with coronary heart disease, and after stimulation and culture with the Notch signaling pathway inhibitor DAPT and the TLR4 agonist CRX-675, the mRNA expression levels of Toll like receptor 2 (TLR2), TLR4, Toll like receptor 9 (TLR9), Notch1, HES1, and HES5 were measured; ELISA was used to measure the levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the supernatant of cell culture; Western blotting was used to measure the relative protein expression levels of TIR domain adaptor molecule (TRIF), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB) p65 subunit in cells. Results Compared with the control group, the three groups of patients with coronary heart disease had significantly higher mRNA expression levels of Notch1,TLR2, TLR4, and TLR9 in peripheral blood mononuc-lear cells, with the highest expression levels in the AMI group (F=10.295-16.558,tLSD=7.918-18.271,P