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.

A Bibliometric and Knowledge-Map Analysis of Macrophage Polarization in Atherosclerosis From 2001 to 2021

“…We conclude that the hotspots of macrophage polarization in AS initially focused on its impact on obesity. Studies explored more critical targets in this area, including Nrf2 ( 59 ), Kruppel-like factor 4 ( 60 – 63 ), GLP-1/GLP-1R ( 64 ), TLR4 ( 27 , 65 ), and micro RNA ( 66 , 67 ), related to inflammation process and plaque progression. Cardiovascular disease studies, including the role of macrophage polarization in lipid metabolism, inflammatory immune response in plaques, and cerebrovascular disease, are two diseases involved in this field.…”

Nonalcoholic Steatohepatitis (NASH) and Atherosclerosis: Explaining Their Pathophysiology, Association and the Role of Incretin-Based Drugs

“…These effects are attributed partly to the glycemic control, weight loss, and subsequent reduction in total cholesterol and triglycerides produced by GLP-1 RAs and also to their anti-inflammatory properties. The latter are related to an inhibition of the expression of pro-inflammatory mediators, such as chemokines and cytokines, as well as a suppression of oxidative stress and endothelium dysfunction, inhibition of monocyte/macrophage infiltration and adhesion, macrophage polarization towards M2, and an inhibition of macrophage transformation to foam cells, all leading to improved plaque stability and impeding plaque progression ( Figure 1 ) [ 159 , 160 , 162 , 163 , 164 , 168 , 169 , 170 ].…”

“…A recent clinical study performed by Yang et al (2021) separated the beneficial CV effect of GLP-1 RAs in terms of atherosclerosis progression from their hypoglycemic effect in patients with coronary heart disease (CHD), indicating that their role is associated with the polarization of macrophages towards M2, i.e., the anti-inflammatory type ( Figure 2 ) [ 159 ]. The anti-inflammatory effect of liraglutide has also been previously reported from preclinical studies [ 160 ].…”

Thiazolidinediones play a positive role in the vascular endothelium and inhibit plaque progression in diabetic patients with coronary atherosclerosis: A systematic review and meta-analysis

“…TZDs treatment could attenuate Diabetes is a major risk factor for coronary heart disease (27), and the mortality rate of coronary heart disease is higher in diabetic patients than in non-diabetic subjects (28). Studies have shown that diabetic patients with concomitant coronary atherosclerosis have more extensive and severe coronary artery lesions (29), which may be associated with disorders of glucose metabolism, disorders of lipid metabolism, inflammatory response, and endothelial damage (30)(31)(32).…”