Maresin1 improves cardiac dysfunction via LGR6 in heatstroke
5 affiliations
- 1Department of Anaesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang China
- 2Department of Critical Care Medicine, Wenzhou People’s Hospital, Wenzhou, Zhejiang China
- 3Department of Pharmacy, Taizhou Women and Children’s Hospital of Wenzhou Medical University, Taizhou, Zhejiang China
- 4Department of Emergency Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang China
- 5Wenzhou Key Laboratory of Precision General Practice and Health Management, Wenzhou, Zhejiang China
Abstract
Heatstroke is a severe and life-threatening condition that can lead to cardiac dysfunction and poses a high risk of mortality. Maresin1, an endogenous lipid mediator, reportedly promotes inflammation resolution in various inflammatory diseases. However, its cardioprotective role during heatstroke has not been thoroughly investigated. In this study, we used ultra-performance liquid chromatography–tandem mass spectrometry to measure the levels of Maresin1 in the plasma and cardiac tissues of mice exposed to heatstroke. Our results indicated a notable decrease in Maresin1 levels under heatstroke conditions. In addition, the levels of leucine-rich repeat-containing G-protein-coupled receptor 6 (LGR6), a receptor for Maresin1, were increased in mice exposed to heatstroke. Exogenously administered Maresin1 significantly improved survival rates and alleviated the symptoms of heatstroke. Conversely, in Lgr6-knockout mice, the symptoms worsened, and the mortality rate increased. Transcriptomic analysis of the cardiac tissue and in vitro experiments have confirmed that Maresin1 exerts cardioprotective effects by inhibiting oxidative stress and promoting ATP synthesis through the upregulation of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α) mediated via LGR6. Nuclear respiratory factor 1 (NRF1) and nuclear respiratory factor 2 (NRF2) were also increased downstream, likely as a secondary response associated with improved mitochondrial biogenesis rather than direct transcriptional regulation by LGR6. Our findings indicate that the Maresin1–LGR6 axis serves a cardioprotective role in heatstroke and is a potential therapeutic target for heatstroke-induced cardiac dysfunction.
Related
- Atorvastatin improves hyperlipidemia-induced erectile dysfunction via PKA-associated eNOS phosphorylation at the Ser633 site
- Sotagliflozin improves cardiac remodeling and is associated with reduced ER stress–related apoptosis and fibrosis in a rat model of mitral regurgitation
- Gui Gan Shen Mai Yin attenuates cardiac hypertrophy and dysfunction in association with mitochondrial homeostasis and the PI3K/AKT1 signaling pathway
- Systemic inflammation induces a myocardial inflammatory transcriptional signature without cardiac dysfunction in murine arthritis
- Multicentre medicoeconomic evaluation of cardiac magnetic resonance imaging for predicting coronary artery disease in left ventricular dysfunction: The CAMAREC study design
BibTeX
@article{jiang2026maresin1,
title = {{Maresin1 improves cardiac dysfunction via LGR6 in heatstroke}},
author = {Ya-ting Jiang and Chen-xi Shen and Suwas Bhandari and Li-ran Su and Fang-jing Ni and Shuang-shuang Li and Bo Feng and Wen-yan Zhang and Lin-feng Liu and Jun Luo and Xiao-dong Pan and Yu-jie Zhou and Hui Li and Yu-qiang Gong and Sheng-wei Jin and Yu Hao},
journal = {Experimental \& Molecular Medicine},
year = {2026},
month = oct,
doi = {10.1038/s12276-026-01853-6},
url = {https://doi.org/10.1038/s12276-026-01853-6},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Maresin1 improves cardiac dysfunction via LGR6 in heatstroke
AU - Ya-ting Jiang
AU - Chen-xi Shen
AU - Suwas Bhandari
AU - Li-ran Su
AU - Fang-jing Ni
AU - Shuang-shuang Li
AU - Bo Feng
AU - Wen-yan Zhang
AU - Lin-feng Liu
AU - Jun Luo
AU - Xiao-dong Pan
AU - Yu-jie Zhou
AU - Hui Li
AU - Yu-qiang Gong
AU - Sheng-wei Jin
AU - Yu Hao
PY - 2026
DA - 2026/10/02
JO - Experimental & Molecular Medicine
DO - 10.1038/s12276-026-01853-6
UR - https://doi.org/10.1038/s12276-026-01853-6
AB - Heatstroke is a severe and life-threatening condition that can lead to cardiac dysfunction and poses a high risk of mortality. Maresin1, an endogenous lipid mediator, reportedly promotes inflammation resolution in various inflammatory diseases. However, its cardioprotective role during heatstroke has not been thoroughly investigated. In this study, we used ultra-performance liquid chromatography–tandem mass spectrometry to measure the levels of Maresin1 in the plasma and cardiac tissues of mice exposed to heatstroke. Our results indicated a notable decrease in Maresin1 levels under heatstroke conditions. In addition, the levels of leucine-rich repeat-containing G-protein-coupled receptor 6 (LGR6), a receptor for Maresin1, were increased in mice exposed to heatstroke. Exogenously administered Maresin1 significantly improved survival rates and alleviated the symptoms of heatstroke. Conversely, in Lgr6-knockout mice, the symptoms worsened, and the mortality rate increased. Transcriptomic analysis of the cardiac tissue and in vitro experiments have confirmed that Maresin1 exerts cardioprotective effects by inhibiting oxidative stress and promoting ATP synthesis through the upregulation of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α) mediated via LGR6. Nuclear respiratory factor 1 (NRF1) and nuclear respiratory factor 2 (NRF2) were also increased downstream, likely as a secondary response associated with improved mitochondrial biogenesis rather than direct transcriptional regulation by LGR6. Our findings indicate that the Maresin1–LGR6 axis serves a cardioprotective role in heatstroke and is a potential therapeutic target for heatstroke-induced cardiac dysfunction.
SN - 1226-3613
SN - 2092-6413
ER -