Metformin ameliorates the progression of atherosclerosis via suppressing macrophage infiltration and inflammatory responses in rabbits

Yang, Qingbiao; Yuan, Hongming; Chen, Mao; Qu, Jiali; Wang, He; Yu, Biao; Chen, Jiahuan; Sun, Shengnan; Tang, Xiaochun; Ren, Wenzhi

doi:10.1016/j.lfs.2018.02.017

Cited by 45 publications

(33 citation statements)

References 42 publications

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“…Moreover, metformin has been reported to restore endothelial function in diabetic status [22,24,25]. In addition, there are evidences supporting an anti-inflammatory effect of metformin particularly in obesity, diabetes and atherosclerosis [21,26,59,60]. Similarly, our results suggested that metformin suppressed inflammatory response induced by high-fat in endothelium.…”

Section: Discussionsupporting

confidence: 74%

High fat-induced inflammation in vascular endothelium can be improved by Abelmoschus esculentus and metformin via increasing the expressions of miR-146a and miR-155

Gou

et al. 2019

Preprint

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Background Obesity is associated with chronic inflammation, which contributes to cardiovascular diseases. MicroRNAs (miRNAs) are reported to be involved in vascular inflammation and atherosclerosis. Abelmoschus esculentus (AE) and metformin have been suggested to improve inflammation in vascular. The aim of this study is to evaluate whether miRNAs are involved in high fat induced endothelial inflammation, and whether AE and metformin improve endothelial inflammation by regulating miRNAs.Methods We established high fat treated rats and human aortic endothelial cells (HAECs). AE and metformin were added to explore their effects on endothelial inflammation induced by high fat and the possible mechanism.Results Rats treated with high fat diet displayed increased inflammation in vascular. The decreased miR-146a and miR-155 were involved in endothelial inflammation induced by high fat by targeting IL-1 receptor-associated kinase 1 (IRAK1), TNF receptor-associated factor 6 (TRAF6) and nuclear factor-κB p65 (NF-κB p65), respectively. While AE and metformin could ameliorate the endothelial inflammation by increasing miR-146a and miR-155.Conclusions These results indicate that miR-146a and miR-155 play roles in the high fat induced endothelial inflammation, which could be potential therapeutic targets, AE and metformin have protective roles to attenuate endothelial inflammation through regulating miR-146a and miR-155.

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Section: Discussionsupporting

confidence: 74%

High fat-induced inflammation in vascular endothelium can be improved by Abelmoschus esculentus and metformin via increasing the expressions of miR-146a and miR-155

Gou

et al. 2019

Preprint

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“…Recent experimental data have shown that metformin inhibited the conversion of monocytes to macrophages and inhibited angiotensin II‐induced atherosclerotic plaque formation, in a strain of genetically engineered mice prone to atherosclerosis . Reduced infiltration of macrophages into the vascular wall, with reduced secretion of inflammatory cytokines, was also observed in a rabbit model of atherogenesis . The effect on angiogenesis in one of these studies and in and in other experimental studies was associated with stimulation of the AMPK/inhibition of mTOR by metformin, which suggests that such a mechanism may be of relevance to the clinical therapeutic action of metformin.…”

Section: Cardiovascular Protection With Metforminmentioning

confidence: 69%

“…112 Reduced infiltration of macrophages into the vascular wall, with reduced secretion of inflammatory cytokines, was also observed in a rabbit model of atherogenesis. 113 The effect on angiogenesis in one of these studies 114 and in and in other experimental studies 115,116 was associated with stimulation of the AMPK/inhibition of mTOR by metformin, which suggests that such a mechanism may be of relevance to the clinical therapeutic action of metformin. Other potentially vascular protective mechanisms described for metformin in experimental studies include reduced cholesterol uptake 117…”

Section: Cellular Antiatherogenic Effectsmentioning

confidence: 93%

Mechanisms of action of metformin with special reference to cardiovascular protection

Zilov

Abdelaziz

Alshammary

et al. 2019

Diabetes Metabolism Res

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Summary Management guidelines continue to identify metformin as initial pharmacologic antidiabetic therapy of choice for people with type 2 diabetes without contraindications, despite recent randomized trials that have demonstrated significant improvements in cardiovascular outcomes with newer classes of antidiabetic therapies. The purpose of this review is to summarize the current state of knowledge of metformin's therapeutic actions on blood glucose and cardiovascular clinical evidence and to consider the mechanisms that underlie them. The effects of metformin on glycaemia occur mainly in the liver, but metformin‐stimulated glucose disposal by the gut has emerged as an increasingly import site of action of metformin. Additionally, metformin induces increased secretion of GLP‐1 from intestinal L‐cells. Clinical cardiovascular protection with metformin is supported by three randomized outcomes trials (in newly diagnosed and late stage insulin‐treated type 2 diabetes patients) and a wealth of observational data. Initial evidence suggests that cotreatment with metformin may enhance the impact of newer incretin‐based therapies on cardiovascular outcomes, an important observation as metformin can be combined with any other antidiabetic agent. Multiple potential mechanisms support the concept of cardiovascular protection with metformin beyond those provided by reduced blood glucose, including weight loss, improvements in haemostatic function, reduced inflammation, and oxidative stress, and inhibition of key steps in the process of atherosclerosis. Accordingly, metformin remains well placed to support improvements in cardiovascular outcomes, from diagnosis and throughout the course of type 2 diabetes, even in this new age of improved outcomes in type 2 diabetes.

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“…Inhibition of atherosclerosis progression by metformin has also been demonstrated recently in an atherogenic diet-induced rabbit atherosclerotic model [ 65 ]. Reduction of macrophage infiltration, inhibition of TNF- α -induced monocyte adhesion, and reduced inflammatory cytokine release from macrophages in endothelial cells were observed in the study [ 65 ].…”

Section: Cardiovascular Protective Effects Of Metforminmentioning

confidence: 99%

Metformin: An Old Drug with New Applications

Zhou

Massey

Story

et al. 2018

IJMS

182

124

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Metformin is a biguanide drug that has been used to treat type 2 diabetes mellitus for more than 60 years. The United Kingdom Prospective Diabetic Study (UKPDS) has shown metformin to improve mortality rates in diabetes patients, and recent studies suggest metformin has additional effects in treating cancer, obesity, nonalcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), and metabolic syndrome. Metformin has also been shown to alleviate weight gain associated with antipsychotic medication. Metformin has recently been extensively studied and emerging evidence suggests metformin decreases hepatocyte triglyceride accumulation in NAFLD and prevents liver tumorigenesis. Interestingly, studies have also shown metformin reduces visceral fat, suppresses white-adipose-tissue (WAT) extracellular matrix remodeling, and inhibits obesity-induced inflammation. However, clinical evidence for using metformin to treat NAFLD, cancer, metabolic syndrome, or to prevent hepatocellular carcinoma in NAFLD patients is lacking. This review therefore addresses the potential beneficial effects of metformin on NAFLD, its role in protecting against cardiac ischemia–reperfusion (I/R) injury, atherosclerosis, glucotoxicity, and lipotoxicity induced oxidative and ER stress in pancreatic β-cell dysfunction, as well as its underlying molecular mechanisms of action.

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Metformin ameliorates the progression of atherosclerosis via suppressing macrophage infiltration and inflammatory responses in rabbits

Cited by 45 publications

References 42 publications

High fat-induced inflammation in vascular endothelium can be improved by Abelmoschus esculentus and metformin via increasing the expressions of miR-146a and miR-155

High fat-induced inflammation in vascular endothelium can be improved by Abelmoschus esculentus and metformin via increasing the expressions of miR-146a and miR-155

Mechanisms of action of metformin with special reference to cardiovascular protection

Metformin: An Old Drug with New Applications

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