Effect of GLP-1/GLP-1R on the Polarization of Macrophages in the Occurrence and Development of Atherosclerosis

Abstract

Aims. To investigate the effect of GLP-1/GLP-1R on the polarization of macrophages in the occurrence and development of atherosclerosis. Methods. Totally, 49 patients with coronary heart disease (CHD) and 52 cases of health control (HC) were recruited, all subjects accept coronary angiography gold standard inspection. One or more major coronary arteries (LM, LAD, LCx, and RCA) stenosis degree in 50% of patients as CHD group; the rest of the stenosis less than 50% or not seen obvious stenosis are assigned to the HC group. Flow cytometry were used to detect the percentage of (CD14+) M macrophages, (CD14+CD80+) M1 macrophages, (CD14+CD206+) M2 macrophages, and their surface GLP-1R expression differences in the two groups, using BD cytokine kit to detect the levels of IL-8, IL-1β, IL-6, IL-10, TNF, and IL-12p70. Results. GLP-1R expression on the surface of total macrophages and M2 macrophages was different between the CHD group and the HC group ( $P<0.05$ ). There was no difference in the percentage of total, M1 or M2 macrophages ( $P>0.05$ ). Concentration of IL-8 in the HC group was higher than that in the CHD group ( $P<0.05$ ). There is no significant difference in the cytokine IL-1β, IL-6, IL-10, TNF, and IL-12p70 in the two groups ( $P>0.05$ ). After controlling for potential confounders including age, gender, smoking status (S.S.), drinking status (D.S.), HR, SBP, DBP, PP, TC, TG, HDL-C, LDL-C, GHbA1c, M, M1, M2, GLP-1R_M, GLP-1R_M1, GLP-1R_M2, IL-8, IL-1β, IL-6, IL-10, TNF, and IL-12p70 by multiple linear regression, decreasing Gensini Score was significantly associated with increased percentage of M1 macrophage. Conclusion. GLP-1R agonist is independent of the hypoglycemic effect of T2DM and has protective effect on cardiovascular system. GLP-1R may regulate the polarization of macrophages toward M2, thus playing a protective role in the progression of coronary atherosclerosis.