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GLP-1/GLP-1R 对动脉粥样硬化发生发展中巨噬细胞极化的影响。

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

机构信息

Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, China.

School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Mediators Inflamm. 2021 Mar 27;2021:5568159. doi: 10.1155/2021/5568159. eCollection 2021.

DOI:10.1155/2021/5568159
PMID:33854404
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8019627/
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-1, 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 ( < 0.05). There was no difference in the percentage of total, M1 or M2 macrophages ( > 0.05). Concentration of IL-8 in the HC group was higher than that in the CHD group ( < 0.05). There is no significant difference in the cytokine IL-1, IL-6, IL-10, TNF, and IL-12p70 in the two groups ( > 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-1, 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.

摘要

目的

探讨 GLP-1/GLP-1R 对动脉粥样硬化发生发展中巨噬细胞极化的影响。

方法

共纳入 49 例冠心病(CHD)患者和 52 例健康对照(HC)患者,所有患者均接受冠状动脉造影金标准检查。将一条或多条主要冠状动脉(LM、LAD、LCx 和 RCA)狭窄程度≥50%的患者归入 CHD 组;其余狭窄程度<50%或未见明显狭窄的患者归入 HC 组。采用流式细胞术检测两组患者(CD14+)M 巨噬细胞、(CD14+CD80+)M1 巨噬细胞、(CD14+CD206+)M2 巨噬细胞及其表面 GLP-1R 表达的差异,采用 BD 细胞因子试剂盒检测白细胞介素(IL)-8、IL-1、IL-6、IL-10、肿瘤坏死因子(TNF)和 IL-12p70 的水平。

结果

CHD 组患者总巨噬细胞和 M2 巨噬细胞表面 GLP-1R 表达与 HC 组不同(<0.05)。两组总、M1 或 M2 巨噬细胞的百分比无差异(>0.05)。HC 组 IL-8 浓度高于 CHD 组(<0.05)。两组细胞因子 IL-1、IL-6、IL-10、TNF 和 IL-12p70 无差异(>0.05)。在校正年龄、性别、吸烟状况(S.S.)、饮酒状况(D.S.)、心率(HR)、收缩压(SBP)、舒张压(DBP)、脉压(PP)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、糖化血红蛋白(GHbA1c)、M、M1、M2、GLP-1R_M、GLP-1R_M1、GLP-1R_M2、IL-8、IL-1、IL-6、IL-10、TNF 和 IL-12p70 等潜在混杂因素后,多元线性回归分析显示,Gensini 评分降低与 M1 巨噬细胞百分比增加显著相关。

结论

GLP-1R 激动剂独立于 T2DM 的降糖作用,对心血管系统具有保护作用。GLP-1R 可能通过调节巨噬细胞向 M2 极化,从而在冠状动脉粥样硬化进展中发挥保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8efb/8019627/0dfee2aa8d91/MI2021-5568159.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8efb/8019627/36f4c937e43c/MI2021-5568159.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8efb/8019627/f8788f23e2ad/MI2021-5568159.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8efb/8019627/f01dc51d6f59/MI2021-5568159.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8efb/8019627/0dfee2aa8d91/MI2021-5568159.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8efb/8019627/36f4c937e43c/MI2021-5568159.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8efb/8019627/f8788f23e2ad/MI2021-5568159.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8efb/8019627/f01dc51d6f59/MI2021-5568159.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8efb/8019627/0dfee2aa8d91/MI2021-5568159.004.jpg

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