ArticleHeliyon2023
Dapagliflozin impedes endothelial cell senescence by activating the SIRT1 signaling pathway in type 2 diabetes.
Article in Heliyon, 2023. 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, 21 citations in OpenAlex.
- Dapagliflozin prevents vascular ischemia-reperfusion injury in healthy young males: a randomized, placebo-controlled, double-blinded trial.Scientific reports · 2025Trial
- Epigenetic dynamics of cellular senescence: From mechanistic insights to precision senotherapy.Chinese medical journal · 2026Review
- Sweet relief: exploring mechanisms and therapeutic approaches of sodium-glucose cotransporter-2 inhibitors in cardiovascular-kidney metabolic syndrome.Cardiovascular diabetology · 2026Review
- Mechanistic Links Between the Gut Microbiome and Longevity Therapeutics.Biomedicines · 2026Review
- Cardiovascular protection by SGLT2 inhibitors: an integrative review of mechanistic networks, clinical evidence, and safety considerations.Frontiers in cardiovascular medicine · 2026Review
- Breaking barriers in pulmonary health of patients with metabolic diseases: senolytics and beyond.Frontiers in aging · 2026Review
- SGLT2 inhibitors as a novel senotherapeutic approach.npj aging · 2025Review
- Impact of sodium-glucose cotransporter-2 inhibitors on pulmonary vascular cell function and arterial remodeling.World journal of cardiology · 2025Review
- Treatment of endothelial cell dysfunction in atherosclerosis: a new perspective integrating traditional and modern approaches.Frontiers in physiology · 2025Review
- Dapagliflozin ameliorates intestinal stem cell aging by regulating the MAPK signaling pathway inFrontiers in cell and developmental biology · 2025Article
- Cellular senescence in age-related cardiovascular disease: past and future.Frontiers in aging · 2025Review
- Review
- Revolutionizing Diabetic Foot Ulcer Care: The Senotherapeutic Approach.Aging and disease · 2024Review
- Aging in Ocular Blood Vessels: Molecular Insights and the Role of Oxidative Stress.Biomedicines · 2024Review
- Article
- SGLT2i improves kidney senescence by down-regulating the expression of LTBP2 in SAMP8 mice.Journal of cellular and molecular medicine · 2024Article
- Antihypertensive Effects of SGLT2-Inhibitors: Considerations for Clinical Practice.Current vascular pharmacology · 2024Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) clinically reduce atherosclerosis and lower blood pressure. However, their impact on endothelial dysfunction in type 2 diabetes (T2D) remains unclear. In this study, we investigated the protective effect and underlying mechanism of the SGLT2 inhibitor dapagliflozin in diabetes. Methods: Vascular reactivity was measured to assess the vasoprotective effect of dapagliflozin in a mouse model of high glucose (HG)-induced T2D. Pulse wave velocity was measured to quantify arterial stiffness. Protein expression was assessed by western blotting and immunofluorescence, oxidative stress was evaluated using dihydroethidium, nitric oxide was evaluated using the Griess reaction, and cellular senescence was assessed based on senescence-associated beta-galactosidase (SA-β-gal) activity and the expression of senescence markers. Furthermore, the endothelial nitric oxide synthase (eNOS) acetylation status was determined and eNOS interactions with SIRT1 were evaluated by coimmunoprecipitation assays. Results: Dapagliflozin protected against impaired endothelium-dependent vasorelaxation and improved arterial stiffness in the mouse model of T2D; mouse aortas had significantly reduced levels of senescence activity and senescence-associated inflammatory factors. HG-induced increases in senescence activity, protein marker levels, and oxidative stress in vitro were all ameliorated by dapagliflozin. The decreases in eNOS phosphorylation and nitric oxide (NO) production in senescent endothelial cells were restored by dapagliflozin. SIRT1 expression was reduced in HG-induced senescent endothelial cells, and dapagliflozin restored SIRT1 expression. SIRT1 inhibition diminished the antisenescence effects of dapagliflozin. Coimmunoprecipitation showed that SIRT1 was physically associated with eNOS, suggesting that the effects of dapagliflozin are dependent on SIRT1 activation. Conclusion: These findings indicate that dapagliflozin protects against endothelial cell senescence by regulating SIRT1 signaling in diabetic mice.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.