ArticleCardiovascular drugs and therapy2022
Empagliflozin Disrupts a Tnfrsf12a-Mediated Feed Forward Loop That Promotes Left Ventricular Hypertrophy.
Article in Cardiovascular drugs and therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 27 citations in OpenAlex.
- Sweet relief: exploring mechanisms and therapeutic approaches of sodium-glucose cotransporter-2 inhibitors in cardiovascular-kidney metabolic syndrome.Cardiovascular diabetology · 2026Review
- Investigating the Role of TNFSF12 in Thyroid Cancer Progression via Single-Cell RNA Sequencing and Integrated Multiomics Analyses.Mediators of inflammation · 2026Article
- Bioinformatic identification of important roles of COL1A1 and TNFRSF12A in cartilage injury and osteoporosis.Journal of the International Society of Sports Nutrition · 2025Article
- Review
- Communication between alveolar macrophages and fibroblasts via the TNFSF12-TNFRSF12A pathway promotes pulmonary fibrosis in severe COVID-19 patients.Journal of translational medicine · 2024Article
- An Exercise Immune Fitness Test to Unravel Disease Mechanisms-A Proof-of-Concept Heart Failure Study.Journal of clinical medicine · 2024Article
- Role and molecular mechanisms of SGLT2 inhibitors in pathological cardiac remodeling (Review).Molecular medicine reports · 2024Review
- Pathophysiological basis of the cardiological benefits of SGLT-2 inhibitors: a narrative review.Cardiovascular diabetology · 2023Review
- Pressure overload induces ISG15 to facilitate adverse ventricular remodeling and promote heart failure.The Journal of clinical investigation · 2023Article
- Sodium-glucose Cotransporter 2 Inhibitors and Pathological Myocardial Hypertrophy.Current drug targets · 2023Article
- Inhibition of activin A receptor signalling attenuates age-related pathological cardiac remodelling.Disease models & mechanisms · 2022Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
purposeAlthough the cardioprotective benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors are now widely appreciated, the mechanisms underlying these benefits remain unresolved. Tumor necrosis factor receptor superfamily member 12a (Tnfrsf12a) is a receptor for tumor necrosis factor superfamily member 12 (Tnfsf12). Tnfrsf12a is highly inducible and plays a key role in the development of cardiac hypertrophy and heart failure. Here we set out to determine if SGLT2 inhibition affects the Tnfsf12/Tnfrsf12a system in the stressed myocardium.
methodsC57BL/6N mice that had undergone sham or transverse aortic constriction (TAC) surgery were treated with either the SGLT2 inhibitor empagliflozin (400 mg/kg diet; 60-65 mg/kg/day) or standard chow alone and were followed for 8 weeks. Tnfrsf12a expression in mouse hearts was assessed by in situ hybridization, qRT-PCR, and immunoblotting.
resultsLeft ventricular (LV) mass, end-systolic volume, and end-diastolic volume were all increased in TAC mice and were significantly lower with empagliflozin. Myocyte hypertrophy and interstitial fibrosis in TAC hearts were similarly attenuated with empagliflozin. Tnfrsf12a expression was upregulated in mouse hearts following TAC surgery but not in the hearts of empagliflozin-treated mice. In cultured cardiomyocytes, Tnfrsf12a antagonism attenuated the increase in cardiomyocyte size that was induced by phenylephrine.
conclusionEmpagliflozin attenuates LV enlargement in mice with hypertrophic heart failure. This effect may be mediated, at least in part, by a reduction in loading conditions which limits upregulation of the inducible, proinflammatory, and prohypertrophic TNF superfamily receptor, Tnfrsf12a. Disruption of the Tnfsf12/Tnfrsf12a feed forward system may contribute to the cardioprotective benefits of SGLT2 inhibition.
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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 Socratic graph.