ArticleCell death discovery2025
Monomethyl fumarate confers cardioprotection after myocardial infarction via HCAR2-dependent activation of PI3K/Akt signaling.
Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- Unfolded Protein Response Pathways in Cancer: Mechanisms, Tumor Biology and Therapeutic Opportunities.Molecular diagnosis & therapy · 2026Review
- Injectable, Conductive, Multifunctional Hydrogels with Sustained Luteolin Release for Promoting Myocardial Infarction Repair.ACS applied materials & interfaces · 2026Article
- Phaseolorin J Alleviates Cellular Inflammation and Oxidative Stress by Inhibiting NLRP3 Inflammasome Expression via the Nrf2/HO-1 Pathway.Marine drugs · 2026Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Monomethyl fumarate (MMF), the active metabolite of dimethyl fumarate, an immunomodulatory drug approved for multiple sclerosis and psoriasis, has emerging potential in ischemic heart disease. We investigated whether MMF can attenuate myocardial infarction (MI) injury and delineated the underlying mechanisms, focusing on hydroxycarboxylic acid receptor 2 (HCAR2, also known as GPR109A) and PI3K/Akt signaling. In a mouse MI model induced by permanent left anterior descending coronary artery ligation, MMF administration prior to ischemia significantly preserved left ventricular function and reduced cardiomyocyte apoptosis compared with untreated MI. Echocardiography and pressure-volume loop analyses demonstrated higher ejection fraction and cardiac output in MMF-treated MI mice, accompanied by attenuation of adverse ventricular remodeling. TUNEL staining and analysis of apoptotic markers showed that MMF decreased myocardial cell death and caspase-3 activation in vivo, while concomitantly upregulating HCAR2 expression and enhancing Akt phosphorylation in ischemic myocardium. In vitro, MMF protected HL-1 cardiomyocytes from CoCl₂-induced hypoxic injury, improving cell viability and reducing apoptosis, as evidenced by fewer TUNEL-positive cells and a lower Bax/Bcl-2 ratio compared with hypoxia alone. Pharmacological inhibition of Gi-coupled signaling with pertussis toxin or siRNA-mediated knockdown of HCAR2 abolished MMF's cytoprotective effects and blunted MMF-induced Akt phosphorylation, and PI3K/Akt pathway inhibition eliminated MMF's anti-apoptotic benefits in vitro. Collectively, these findings demonstrate that MMF markedly reduces ischemic cardiomyocyte injury via an HCAR2-dependent mechanism involving activation of the pro-survival PI3K/Akt pathway, establishing a novel cardioprotective role for MMF and supporting its translational potential as a therapeutic strategy to mitigate acute MI injury.
Identifiers
What Socratic holds
Registered trials
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.