Qiangbing Yang1, Hongming Yuan1, Mao Chen1, Jiali Qu1, He Wang1, Biao Yu1, Jiahuan Chen1, Shengnan Sun1, Xiaochun Tang1, Wenzhi Ren2. 1. Jilin Provincial Model Animal Engineering Research Center, College of Animal Sciences, Jilin University, Changchun 130062, China. 2. Jilin Provincial Model Animal Engineering Research Center, College of Animal Sciences, Jilin University, Changchun 130062, China. Electronic address: rwz1964@163.com.
Abstract
AIMS: The present study aimed to investigate the possible effects of metformin on the progression of atherosclerosis in a rabbit model. MAIN METHODS: Rabbits were randomly divided into three groups (n = 10): the control (Ctrl) group (fed with a chow diet), and two experimental groups, the AS group and the Met group (both received an atherogenic diet). After 2 weeks of acclimatization, the rabbits in the AS and Met groups were given a placebo and metformin, respectively, daily by gavage for 10 weeks. Plasma lipids and inflammatory cytokines were measured. The aorta was isolated for histological and immunohistochemical analysis. In vitro, human umbilical vein endothelial cells (HUVECs) were treated with metformin, and monocyte adhesion and adhesion molecule expression were measured. KEY FINDINGS: Metformin reduced plasma inflammatory cytokine levels but did not alter lipid content. Compared with that in the AS group, the atherosclerosis burden in the Met group was significantly decreased. The lesional macrophage content was reduced, but the lesional collagen content was not affected in the metformin-treated rabbits, compared with the corresponding levels in the non-treated controls. Furthermore, the aortic mRNA expression levels of adhesion molecules and inflammatory cytokines in the Met group were also significantly reduced compared with those in the AS group. Metformin treatment reduced monocyte adhesion to endothelial cells (ECs) and adhesion molecule expression, and inhibited rabbit monocyte differentiation into macrophages and the macrophage inflammatory response. SIGNIFICANCE: Our results suggest that metformin impeded the progression of atherosclerosis, possibly by suppressing macrophage infiltration and inflammatory responses.
AIMS: The present study aimed to investigate the possible effects of metformin on the progression of atherosclerosis in a rabbit model. MAIN METHODS:Rabbits were randomly divided into three groups (n = 10): the control (Ctrl) group (fed with a chow diet), and two experimental groups, the AS group and the Met group (both received an atherogenic diet). After 2 weeks of acclimatization, the rabbits in the AS and Met groups were given a placebo and metformin, respectively, daily by gavage for 10 weeks. Plasma lipids and inflammatory cytokines were measured. The aorta was isolated for histological and immunohistochemical analysis. In vitro, human umbilical vein endothelial cells (HUVECs) were treated with metformin, and monocyte adhesion and adhesion molecule expression were measured. KEY FINDINGS:Metformin reduced plasma inflammatory cytokine levels but did not alter lipid content. Compared with that in the AS group, the atherosclerosis burden in the Met group was significantly decreased. The lesional macrophage content was reduced, but the lesional collagen content was not affected in the metformin-treated rabbits, compared with the corresponding levels in the non-treated controls. Furthermore, the aortic mRNA expression levels of adhesion molecules and inflammatory cytokines in the Met group were also significantly reduced compared with those in the AS group. Metformin treatment reduced monocyte adhesion to endothelial cells (ECs) and adhesion molecule expression, and inhibited rabbit monocyte differentiation into macrophages and the macrophage inflammatory response. SIGNIFICANCE: Our results suggest that metformin impeded the progression of atherosclerosis, possibly by suppressing macrophage infiltration and inflammatory responses.
Authors: Alexey V Zilov; Sulaf Ibrahim Abdelaziz; Afaf AlShammary; Ali Al Zahrani; Ashraf Amir; Samir Helmy Assaad Khalil; Kerstin Brand; Nabil Elkafrawy; Ahmed A K Hassoun; Adel Jahed; Nadim Jarrah; Sanaa Mrabeti; Imran Paruk Journal: Diabetes Metab Res Rev Date: 2019-07-24 Impact factor: 4.876