Researchers from Lleida contribute to the discovery of a new natural mechanism that protects the heart after a heart attack

An international team led by the China Pharmaceutical University, with the participation of the Cell Signalling and Apoptosis research group from the University of Lleida (UdL) and the Biomedical Research Institute of Lleida (IRBLleida), has identified a new mechanism that helps protect the heart after myocardial infarction. The findings, published in the British Journal of Pharmacology, reveal how communication between different cell types contributes to limiting cardiac damage and promoting the recovery of injured tissue.

The researchers discovered that the EXT1 protein enables immune cells to deliver antioxidant molecules to cardiac tissue, helping to reduce damage and improve recovery. "The results suggest that this mechanism could be enhanced using drugs, representing a promising strategy to reduce cardiac complications after a heart attack," explained Daniel Sanchis, professor at UdL and researcher at IRBLleida.

Every year, millions of people worldwide suffer a myocardial infarction. Despite advances in treatment, a significant portion of cardiac damage occurs in the days following the acute event, when injured tissue undergoes oxidative stress and remodelling processes that can ultimately weaken heart function.

The researchers found that a protein called EXT1, present in heart muscle cells (cardiomyocytes), facilitates the accumulation of antioxidant molecules released by immune cells in cardiac tissue, helping to reduce damage and promote recovery. Through this mechanism, an antioxidant protein called SOD2, released by macrophages, can accumulate in injured cardiac tissue. This protein helps reduce oxidative stress and limits the damage caused after a heart attack.

In addition, the results show that the molecule dimethyl itaconate (DMI) stimulates macrophages to release higher amounts of SOD2, thereby enhancing heart protection. In animal models of myocardial infarction, this treatment reduced cardiac damage and fibrosis.

"The findings open up a new line of research aimed at strengthening the heart's natural defence mechanisms after a heart attack. Although this is still preclinical research and further studies will be needed before clinical application, the identification of the EXT1-heparan sulfate-SOD2 axis could contribute to the development of future strategies to reduce the cardiac complications associated with this disease," explained Marta Llovera, professor at UdL and researcher at IRBLleida.

The participation of UdL and IRBLleida in this work was carried out within the framework of a project funded by the Spanish Ministry of Science, Innovation and Universities (MICIU), further strengthening the institute's international collaboration in cardiovascular research.

Article: Li X, Lin Y, Xu X, Li Y, Hu J, Liu M, Jia S, Shao Y, Llovera M, Yan F, Li R, Sheng Y, Jin L, Sanchis D, Ye J. EXT1 in cardiomyocytes promotes heparan sulphate-dependent accumulation of macrophage-derived SOD2 to protect against post-myocardial infarction injury. Br J Pharmacol. 2026 Sep 20. doi: 10.1111/bph.70663. Epub ahead of print. PMID: 42764678.