ArticleCardiovascular diabetology2014
Activation of AMP-activated protein kinase by metformin protects human coronary artery endothelial cells against diabetic lipoapoptosis.
Article in Cardiovascular diabetology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 38 citations in OpenAlex.
- Metformin, Cognitive Function, and Changes in the Gut Microbiome.Endocrine reviews · 2024Review
- Overcoming chemoresistance in non-angiogenic colorectal cancer by metformin via inhibiting endothelial apoptosis and vascular immaturity.Journal of pharmaceutical analysis · 2023Article
- Review
- Metformin alleviates monoamine oxidase-related vascular oxidative stress and endothelial dysfunction in rats with diet-induced obesity.Molecular and cellular biochemistry · 2021Article
- AMPK: Potential Therapeutic Target for Vascular Calcification.Frontiers in cardiovascular medicine · 2021Review
- Metformin in cardiovascular diabetology: a focused review of its impact on endothelial function.Theranostics · 2021Review
- Metformin attenuates cartilage degeneration in an experimental osteoarthritis model by regulating AMPK/mTOR.Aging · 2020Article
- The Vascular Consequences of Metabolic Syndrome: Rodent Models, Endothelial Dysfunction, and Current Therapies.Frontiers in pharmacology · 2020Review
- 17β-Estradiol Induces Mitophagy Upregulation to Protect ChondrocytesFrontiers in endocrinology · 2020Article
- Metformin in patients with and without diabetes: a paradigm shift in cardiovascular disease management.Cardiovascular diabetology · 2019Review
- Metformin triggers the intrinsic apoptotic response in human AGS gastric adenocarcinoma cells by activating AMPK and suppressing mTOR/AKT signaling.International journal of oncology · 2019Article
- Article
- Metformin improves circulating endothelial cells and endothelial progenitor cells in type 1 diabetes: MERIT study.Cardiovascular diabetology · 2016Article
- Metformin improves the angiogenic functions of endothelial progenitor cells via activating AMPK/eNOS pathway in diabetic mice.Cardiovascular diabetology · 2016Article
- Metformin regulates oxLDL-facilitated endothelial dysfunction by modulation of SIRT1 through repressing LOX-1-modulated oxidative signaling.Oncotarget · 2016Article
- Metformin improves the angiogenic potential of human CD34⁺ cells co-incident with downregulating CXCL10 and TIMP1 gene expression and increasing VEGFA under hyperglycemia and hypoxia within a therapeutic window for myocardial infarction.Cardiovascular diabetology · 2016Article
- Effect of metformin monotherapy on cardiovascular diseases and mortality: a retrospective cohort study on Chinese type 2 diabetes mellitus patients.Cardiovascular diabetology · 2015Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe prevalence of type 2 diabetes (T2D) among adults worldwide is rapidly increasing, and in patients with diabetes the major cause of death is macrovascular disease. Endothelial cells play an important role in maintaining vascular homeostasis. Free fatty acids, which are elevated in T2D, have previously been shown to induce endothelial dysfunction and apoptosis of endothelial cells, which is considered as an important and early factor in the onset of atherosclerosis and cardiovascular disease. Metformin, which is used as first line treatment of T2D patients, is believed to exert its pharmacological effects through activation of AMP-activated protein kinase, which has emerged as a new potential target in reversing endothelial dysfunction.
methodsHere we studied the protective effect of metformin against free fatty acid-induced apoptosis of human coronary artery endothelial cells (HCAECs) by assessing DNA fragmentation and cleaved caspase 3 levels. We also attempted to elucidate the underlying mechanisms by investigating the involvement of AMP-activated protein kinase, p38 MAPK and eNOS. Generation of reactive oxygen species by free fatty acid exposure was also examined.
resultsOur results suggest that metformin protects HCAECs from lipoapoptosis, an effect that involves eNOS and p38 MAPK, downstream of AMPK signaling, but not as previously suggested through suppression of reactive oxygen species.
conclusionThe protective effect of metformin against free fatty acid induced apoptosis is potentially clinically relevant as metformin is first line treatment for patients with T2D, a patient group which is rapidly increasing and carries a high burden of cardiovascular disease.
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