UHPLC-MS/MS Tracks Maresin1 in Heatstroke Hearts

Heatstroke is a dangerous, potentially deadly condition that can damage the heart. Maresin1, a fat-based molecule the body makes naturally, is known to help calm inflammation in several diseases, but scientists do not yet know much about whether it can protect the heart during heatstroke. To find out, researchers used ultrahigh-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS), to measure how much Maresin1 was in the blood and heart tissue of mice with heatstroke. A paper based on their research was published in the journal Experimental & Molecular Medicine.¹

What is Already Known About How Maresin1 Protects the Heart, and What Questions Remain?

In research involving mice that have had a heart attack, Maresin1 has been reported to help the heart heal more normally and keep a steadier rhythm. It appears to do this by switching on the body's natural defenses against cell damage and calming harmful inflammation. In practice, that means fewer inflammatory signals are released, fewer heart muscle cells die, and less scar tissue builds up in the heart. ^14,17.

Still, scientists do not yet know exactly which cells Maresin1 works through (whether they are heart muscle cells, the cells lining blood vessels, or immune cells). The authors of the paper report that most research so far has looked at how it reduces inflammation by attaching to certain receptors, such as one called ALX/FPR2, but there is no solid proof that these same receptors are behind its heart-protecting effects.¹

There are other open questions, too. In heart conditions such as heart attack, heart failure, and diabetes-related heart disease, it is not clear whether the body naturally makes enough Maresin1 to make a difference at each stage of the illness. Researchers also have not worked out the best timing or dose for giving extra Maresin1 as a treatment. In addition, exactly how Maresin1 protects the heart, especially during heatstroke, still has not been studied in much depth.¹

What Did the Researchers Discover about Maresin1's Role in Protecting the Heart During Heatstroke?

The researchers found that Maresin1 levels dropped sharply during heatstroke. At the same time, mice with heatstroke had more LGR6, the receptor that Maresin1 attaches to in order to do its job. When the mice were given extra Maresin1, more of them survived and their heatstroke symptoms eased. On the other hand, mice bred without the LGR6 receptor got sicker and were more likely to die.¹

By looking at which genes were switched on in heart tissue and running follow-up experiments on cells in the lab, the team confirmed how Maresin1 protects the heart. Working through LGR6, it boosts a protein called PGC1α, which helps cells cut down on damaging oxidative stress and produce more energy. Two related proteins, NRF1 and NRF2, also increased. This rise is likely a knock-on effect of the cells' energy-producing machinery working better, rather than something LGR6 controls directly.¹

“Our findings,” write the authors of the paper,¹ “indicate that the Maresin1-LGR6 axis serves a cardioprotective role in heatstroke and is a potential therapeutic target for heatstroke-induced cardiac dysfunction.”

The researchers admit that their study does have some limitations. Most importantly, it was done in mice, so it is not yet known whether the results apply to people. Studies in humans will be needed to confirm them. In addition, the mice used in the study were missing the LGR6 receptor throughout their entire bodies, which let the researchers study how Maresin1 and LGR6 work together to protect the heart during heatstroke. Using mice that lack LGR6 only in their heart muscle cells would give a clearer picture of what the receptor does specifically in the heart.¹

References

• Jiang, Y. T.; Shen, C. X.; Bhandari, S. et al. Maresin1 Improves Cardiac Dysfunction via LGR6 in Heatstroke. Exp Mol Med. 2026. DOI: 10.1038/s12276-026-01853-6
• Wang, F.; Gong, Y.; Chen, T. et al. Maresin1 Ameliorates Ventricular Remodelling and Arrhythmia in Mice Models of Myocardial Infarction via NRF2/HO-1 and TLR4/NF-kB Signalling. Int Immunopharmacol. 2022, 113 (Pt A), 109369. DOI: 10.1016/j.intimp.2022.109369
• Liu, M.; He, H.; Chen, L. Protective Potential of Maresins in Cardiovascular Diseases. Front Cardiovasc Med. 2022, 9, 923413. DOI: 10.3389/fcvm.2022.923413