ArticleCardiovascular drugs and therapy2021
Metformin Is Associated with Reduced Tissue Factor Procoagulant Activity in Patients with Poorly Controlled Diabetes.
Article in Cardiovascular drugs and therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Characterization of Biomarkers of Thrombo-Inflammation in Patients with First-Diagnosed Atrial Fibrillation.International journal of molecular sciences · 2024Article
- Mechanisms of endothelial activation, hypercoagulation and thrombosis in COVID-19: a link with diabetes mellitus.Cardiovascular diabetology · 2024Review
- Emerging roles of microRNAs as diagnostics and potential therapeutic interest in type 2 diabetes mellitus.World journal of clinical cases · 2024Article
- Enhancing the anticancer potential of metformin: fabrication of efficient nanospanlastics,International journal of pharmaceutics: X · 2023Article
- Intestinal Barrier Dysfunction and Microbial Translocation in Patients with First-Diagnosed Atrial Fibrillation.Biomedicines · 2023Article
- Vascular endothelial tissue factor contributes to trimethylamine N-oxide-enhanced arterial thrombosis.Cardiovascular research · 2022Article
- Protection by metformin against severe Covid-19: An in-depth mechanistic analysis.Diabetes & metabolism · 2022Review
- How Diabetes and Other Comorbidities of Elderly Patients and Their Treatment Influence Levels of Glycation Products.International journal of environmental research and public health · 2022Article
- Metformin inhibits melanoma cell metastasis by suppressing the miR-5100/SPINK5/STAT3 axis.Cellular & molecular biology letters · 2022Article
- Therapeutic Strategies Focused on Cancer-Associated Hypercoagulation for Ovarian Clear Cell Carcinoma.Cancers · 2022Review
- Structural Comparison of Sulfonamide-Based Derivatives That Can Improve Anti-Coagulation Properties of Metformin.International journal of molecular sciences · 2022Article
- Expression of whole blood miR-126-3p, -30a-5p, -1299, -182-5p and -30e-3p in chronic kidney disease in a South African community-based sample.Scientific reports · 2022Article
- Hypofibrinolysis in type 2 diabetes and its clinical implications: from mechanisms to pharmacological modulation.Cardiovascular diabetology · 2021Review
- Prognostic value of subclinical myocardial necrosis using high-sensitivity cardiac troponin T in patients with prediabetes.Cardiovascular diabetology · 2021Article
- Effects of Hyperglycemia and Diabetes Mellitus on Coagulation and Hemostasis.Journal of clinical medicine · 2021Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
purposeMetformin is the first-line antidiabetic drug and shown to reduce cardiovascular risk independent from its glucose lowering action. Particularly in poorly controlled diabetes, tissue factor (TF) is expressed in the vasculature and accounts for thromboembolic complications. Here, we aimed to assess the effect of metformin on TF activity and markers of vascular inflammation in poorly controlled type 2 diabetes.
methodsIn a cohort of patients with uncontrolled type 2 diabetes (glycosylated hemoglobin 8.39 ± 0.24%, 68.1 ± 2.6 mmol/mol, n = 46) of whom half of the individuals were treated with metformin and the other half did not receive metformin as part of an anti-diabetic combination therapy, we assessed TF activity and markers of vascular inflammation. In vitro, human monocytic cells (THP-1) were exposed to metformin and TF expression measured in the presence and absence of the AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide riboside (AICAR) or the AMPK inhibitor compound C.
resultsIn the patients, metformin treatment was associated with lower levels of TF protein (241.5 ± 19 vs. 315.4 ± 25 pg/mL, p = 0.03) and reduced TF activity (408.9 ± 49 vs. 643.8 ± 47 U/mL, p = 0.001) compared with controls. Moreover, the patients on metformin showed lower levels of vascular cell adhesion molecule (VCAM)1 (26.6 ± 1.4 vs. 35.03 ± 3.1 ng/mL, p = 0.014) and higher expression of miR-126-3p/U6sno (11.39 ± 2.8 vs. 4.26 ± 0.9, p = 0.006), a known post-transcriptional down regulator of TF and VCAM1. In vitro, metformin dose-dependently reduced lipopolysaccharide (LPS)-induced TF expression in THP-1 cells. The AMPK activator AICAR alone lowered TF expression in THP-1, while the AMPK inhibitor compound C abrogated the metformin-dependent reduction in TF expression.
conclusionsOur data are the first to report that metformin is associated with reduced plasma TF procoagulant activity possibly explaining-at least in part-the vasculoprotective properties of metformin.
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