Expression Of SGK1/RAC1 Pathway In Peripheral Blood Mononuclear Cells Of Patients With Coronary Heart Disease And Its Role In Foam Cell Transformation

Objective:The recruitment of monocytes/macrophages into the subendothelial space to remove lipids is an important pathophysiological process of early coronary atherosclerosis.High expression of serum/glucocorticoid regulated protein kinase 1(SGK1)in macrophages can promote the progression of atherosclerosis by activating Rho GTP family to regulate macrophage invasion and phagocytosis.The purpose of this study was to detect the expression of SGK1/Ras-related C3 botulinum toxin substrate 1(RAC1)pathway related proteins in peripheral blood monocytes of patients with coronary heart disease.RAW264.7 cells were used to verify the effect of SGK1/RAC1 pathway expression level on macrophage phagocytosis.Methods:From October 2018 to October 2020,40 patients with stable coronary heart disease diagnosed for the first time by percutaneous coronary angiography or coronary artery contrast-enhanced CT without lipid-lowering therapy in the Affiliated Hospital of Hangzhou Normal University were included.At the same time,40 patients with similar age and no atherosclerotic disease confirmed by imaging examination were selected as the control group.Blood samples were collected from all patients to detect biochemical function,and peripheral blood monocytes were extracted to detect the expression of SGK1/RAC1.RAW264.7 cells were used to construct SGK1 high expression group and SGK1 low expression group model,and foam cells were induced by ox LDL.The content of lipid in cells was observed by oil red O staining,and the expression level of SGK1/RAC1 pathway protein was detected by Western blotting.It was used to speculate the effect of SGK1/RAC1 pathway on the transformation of monocytes into foam cells.Results:The levels of total cholesterol and triglyceride in coronary heart disease group were significantly higher than those in control group,and the protein expression levels of SGK1 and Rac1 in peripheral blood mononuclear macrophages were significantly higher than those in control group(SGK1: coronary heart disease group was 72.28±12.04% vs.44.02±31.70%,P = 0.04;Rac1: coronary heart disease group was 126.43±70.14% vs.37.76±26.37%,P = 0.03).The foam cells were induced by RAW264.7.The lipid content in the SGK1 high expression group was significantly higher than that in the simple foam cell group(the lipid content in each cell was 5360.83±257.36 vs.1728.46±227.41,P < 0.01).In SGK1 low expression group,the lipid content in each cell was significantly lower than that in the simple foam cell group(the lipid content in each cell was 127.16±2.65 vs.1728.46±227.41,P < 0.01).Western-Blot results showed that the expression levels of RAC1 and ARP2/3 protein in SGK1 high expression group were significantly higher than those in standard foam cell group,while that in SGK1 low expression group decreased significantly.Conclusion:The SGK1/RAC1 pathway plays an important role in the transformation of macrophages into foam cells,and may be a potential target for early coronary atherosclerosis.