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Metformin in cardiovascular diabetology: a focused review of its impact on endothelial function
Journal article   Open access   Peer reviewed

Metformin in cardiovascular diabetology: a focused review of its impact on endothelial function

Yu Ding, Yongwen Zhou, Ping Ling, Xiaojun Feng, Sihui Luo, Xueying Zheng, Peter J Little, Suowen Xu and Jianping Weng
Theranostics, Vol.11(19), pp.9376-9396
2021
PMCID: PMC8490502
PMID: 34646376
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Metformin in cardiovascular diabetology a focused review of its impact on endothelial function1.06 MBDownloadView
Published Version Open Access CC BY V4.0
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https://doi.org/10.7150/thno.64706View
Published Version

Abstract

Diabetes Cardiovascular diabetology Endothelial function Metformin Panvascular disease
As a first-line treatment for diabetes, the insulin-sensitizing biguanide, metformin, regulates glucose levels and positively affects cardiovascular function in patients with diabetes and cardiovascular complications. Endothelial dysfunction (ED) represents the primary pathological change of multiple vascular diseases, because it causes decreased arterial plasticity, increased vascular resistance, reduced tissue perfusion and atherosclerosis. Caused by "biochemical injury", ED is also an independent predictor of cardiovascular events. Accumulating evidence shows that metformin improves ED through liver kinase B1 (LKB1)/5'-adenosine monophosphat-activated protein kinase (AMPK) and AMPK-independent targets, including nuclear factor-kappa B (NF-κB), phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), endothelial nitric oxide synthase (eNOS), sirtuin 1 (SIRT1), forkhead box O1 (FOXO1), krüppel-like factor 4 (KLF4) and krüppel-like factor 2 (KLF2). Evaluating the effects of metformin on endothelial cell functions would facilitate our understanding of the therapeutic potential of metformin in cardiovascular diabetology (including diabetes and its cardiovascular complications). This article reviews the physiological and pathological functions of endothelial cells and the intact endothelium, reviews the latest research of metformin in the treatment of diabetes and related cardiovascular complications, and focuses on the mechanism of action of metformin in regulating endothelial cell functions.

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