A research team from the Lewis Katz School of Medicine at Temple University has discovered that reactivating the PSAT1 gene may promote the repair of damaged cardiac tissue and improve heart function following a heart attack. This study, published in the journal Theranostics, offers new insights into regenerative therapies for ischemic heart disease.

Led by Dr. Raj Kishore, the team used synthetic modified messenger RNA (modRNA) technology to deliver the PSAT1 gene to the hearts of adult mice. Results showed that treated mice exhibited significantly enhanced cardiomyocyte proliferation, reduced scar tissue, improved angiogenesis, and marked recovery of cardiac function. Dr. Kishore stated: "The PSAT1 gene is highly active during developmental stages but is nearly silenced in adult hearts. Our research indicates that reactivating it could aid cardiac repair."

The mechanism of PSAT1 involves activating the serine synthesis pathway (SSP), which reduces oxidative stress and DNA damage, thereby protecting cardiomyocytes. Additionally, PSAT1 is regulated by YAP1 and promotes nuclear translocation of β-catenin, further driving cardiomyocyte regeneration. The study also found that inhibiting SSP counteracts the repair effects of PSAT1, confirming the critical role of this pathway.

The application of modRNA technology opens new possibilities for cardiac regenerative therapy. Unlike viral vectors, modRNA does not integrate into the genome, reducing long-term risks. Dr. Kishore noted: "This study lays the foundation for developing mRNA-based strategies for cardiac repair." In the future, the team plans to optimize the safety and delivery methods of PSAT1 therapy in large animal models to advance clinical translation.