Protective effects of metformin in various cardiovascular diseases: Clinical evidence and <scp>AMPK</scp>‐dependent mechanisms

Bu, Yizhi; Peng, Mei; Tang, Xinyi; Xu, Xu; Wu, Yue; Chen, Alex F.; Yang, Xiaoping

doi:10.1111/jcmm.17519

Cited by 30 publications

(15 citation statements)

References 147 publications

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“…Its downregulation could represent a feedback mechanism for controlling the overactivation of immune cells. According to a previous mouse model study with atherosclerosis, the expression of miRNA-155-5p decreases in these cells in response to inflammation, and thus it could be associated with the formation of atherosclerotic plaque [38].…”

Section: Discussionmentioning

confidence: 94%

Overexpression of microRNA-21-5p and microRNA-221-5p in Monocytes Increases the Risk of Developing Coronary Artery Disease

Torres-Paz

Gamboa

Fuentevilla-Álvarez

et al. 2023

IJMS

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MicroRNAs (miRs) regulate gene expression at the post-transcriptional level and are found to be present in monocytes. This study aimed to investigate miR-221-5p, miR-21-5p, and miR-155-5p, their expression in monocytes, and their role in coronary arterial disease (CAD). The study population comprised 110 subjects, and RT-qPCR was used to examine the miR-221-5p, miR-21-5p, and miR-155-5p expressions in monocytes. Results: the miR-21-5p (p = 0.001) and miR-221-5p (p < 0.001) expression levels were significantly higher in the CAD group, and the miR-155-5p (p = 0.021) expression levels were significantly lower in the CAD group; only miR-21-5p and miR-221-5p upregulation was found to be associated with an increased CAD risk. The results show significant increases in miR-21-5p in the unmedicated CAD group with the metformin patients vs. the healthy control group (p = 0.001) and vs. the medicated CAD group with metformin (p = 0.022). The same was true for miR-221-5p in the CAD patients unmedicated with metformin vs. the healthy control group (p < 0.001). Our results from Mexican CAD patients show that the overexpression in monocytes of miR-21-5p and miR-221-5p increases the risk of the development of CAD. In addition, in the CAD group, the metformin downregulated the expression of miR-21-5p and miR-221-5p. Also, the expression of endothelial nitric oxide synthase (NOS3) decreased significantly in our patients with CAD, regardless of whether they were medicated. Therefore, our findings allow for the proposal of new therapeutic strategies for the diagnosis and prognosis of CAD and the evaluation of treatment efficacy.

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Section: Discussionmentioning

confidence: 94%

Overexpression of microRNA-21-5p and microRNA-221-5p in Monocytes Increases the Risk of Developing Coronary Artery Disease

Torres-Paz

Gamboa

Fuentevilla-Álvarez

et al. 2023

IJMS

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“…In a series of studies such as the prevention of rheumatoid arthritis, metformin has been shown to not only lower blood glucose, but also reduce body weight and indirectly inhibit inflammation by altering the intestinal flora, thus reducing the risk of developing a number of diseases [ 20 – 24 ]. Available studies have demonstrated that metformin acts not only through AMP-activated protein kinase, but also through mitochondrial complex 1, growth differentiation factor 15, and glucagon-like peptide 1/glucagon [ 25 – 28 ]. At the same time, many basic studies have demonstrated that metformin can play a cardiovascular protective role by reducing endothelial dysfunction and reducing oxidative stress to improve inflammation [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Causal association of metformin treatment with diverse cardiovascular diseases: a Mendelian randomization analysis

Li,

Liu,

et al. 2024

Aging

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Background: The cardiovascular effects of metformin continue to be a subject of debate within the medical community. Methods: The Mendelian randomization (MR) study used data from genome-wide association studies (GWAS) to explore the causal association with six diseases that are associated with bimatoprost treatment and myocardial infarction, chronic heart failure, atrial fibrillation, hypertrophic and dilated cardiomyopathy, and valvular disease. Genome-wide significant single nucleotide polymorphisms (SNPs), that are associated with metformin use were selected as the instrumental variables. To determine the causal relationship between metformin use and various cardiovascular diseases, MR analysis was conducted, employing methods such as Instrumental Variable Weighting (IVW). Results: The IVW analysis demonstrated a positive association between metformin treatment and the risk of myocardial infarction (OR = 22.67, 95% CI 3.22–34.01; P = 0.002). Conversely, metformin treatment exhibited a negative association with the risk of developing valvular disease (OR = 0.98, 95% CI 0.95–1.00; P = 0.046) and hypertrophic cardiomyopathy (OR = 0.01, 95% CI 0.00–0.22; P = 0.016). Multiple test correction found that metformin treatment was causally associated with the risk of both hypertrophic cardiomyopathy ( P FDR = 0.048) and myocardial infarction ( P FDR = 0.012). The analysis revealed limited heterogeneity in the individual results, absence of pleiotropy evidence, and indications of stability in the findings. Conclusion: The MR study discovered from a genetic standpoint that metformin may lower the risk of hypertrophic cardiomyopathy and valvular heart disease, yet it could elevate the risk of myocardial infarction.

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“…Considering drug development, the diverse nature of AMPK has given rise to concerns regarding potential unintended outcomes when targeting it. While potent pan-β activators have been linked to cardiac hypertrophy in non-human primates, 121 clinical investigations centered on type 2 diabetes and/or cardiovascular disease have indicated that judicious use of AMPK activators proves both safe and efficacious.…”

Section: Discussionmentioning

confidence: 99%

The Role of AMPK Signaling in Ulcerative Colitis

Yuan,

Wang,

Liu

et al. 2023

DDDT

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Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease characterized by inflammation and ulcer formation of the intestinal mucosa. Due to its high recurrence rate, prolonged course, limited curative options, and significant impact on patients’ quality of life, along with a notable potential for malignant transformation, UC is designated as a refractory global health challenge by the World Health Organization (WHO). The elucidation of the pathogenesis and therapeutic strategies for UC requires further in-depth investigation. AMP-activated protein kinase (AMPK) serves as a central regulator of cellular energy metabolic homeostasis. Emerging evidence indicates that interventions involving traditional Chinese medicine (TCM) components, as well as other pharmacological measures, exert beneficial effects on the intestinal mucosal inflammation and epithelial barrier dysfunction in UC by modulating AMPK signaling, thereby influencing biological processes such as cellular autophagy, apoptosis, inflammatory responses, macrophage polarization, and NLRP3 inflammasome-mediated pyroptosis. The role of AMPK in UC is of significant importance. This manuscript provides a comprehensive overview of the mechanisms through which AMPK is involved in UC, as well as a compilation of pharmacological agents capable of activating the AMPK signaling pathway within the context of UC. The primary objective is to facilitate a deeper comprehension of the pivotal role of AMPK in UC among researchers and clinical practitioners, thereby advancing the identification of novel therapeutic targets for interventions in UC.

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Protective effects of metformin in various cardiovascular diseases: Clinical evidence and AMPK‐dependent mechanisms

Cited by 30 publications

References 147 publications

Overexpression of microRNA-21-5p and microRNA-221-5p in Monocytes Increases the Risk of Developing Coronary Artery Disease

Overexpression of microRNA-21-5p and microRNA-221-5p in Monocytes Increases the Risk of Developing Coronary Artery Disease

Causal association of metformin treatment with diverse cardiovascular diseases: a Mendelian randomization analysis

The Role of AMPK Signaling in Ulcerative Colitis

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