Maresin 1 Attenuates Myocardium Ischemia/Reperfusion Injury via SIRT1/HMGB-1/NLRP-3-Related Mechanisms.

Background And Purpose: Maresin 1 (MaR 1) has demonstrated potent anti-inflammatory and antioxidant effects in different animal models. However, its impact on heart ischemia/reperfusion injury (IRI) remains uncertain. Pyroptosis, a pro-inflammatory programmed cell death, is associated with IRI. The goal of our research was to assess the role of MaR 1 on pyroptosis during heart IRI mice.

Methods: Cardiac IRI was induced in a mouse model, and hypoxia/reoxygenation (H/R) was conducted on neonatal rat ventricle myocytes (NRVMs) to establish an in vitro model. The effects of MaR 1 were assessed using measures such as cardiac infarct area, heart tissue injury, hemodynamic monitoring, apoptotic index, pyroptosis-related proteins, inflammatory reaction and heart enzyme activities.

Results: MaR 1 injection obviously reduced cardiac infarct area and apoptosis, inhibited myocardial pyroptosis, decreased pro-inflammatory cytokines and suppressed apoptosis via Silent information regulator factor 2-related enzyme 1 (SIRT1). Additionally, MaR 1 injection markedly suppressed the expression of High-mobility group box 1 (HMGB-1)/nuclear factor-κB (NF-κB)/(NOD)-like receptor Pyrin domain-containing 3 (NLRP-3) axis-related proteins by SIRT1. In isolated NRVMs, MaR 1 increased cellular viability, diminished heart enzyme activities and inhibited apoptosis and inflammation. Furthermore, in vitro studies demonstrated that the SIRT1 inhibitor decreased the anti-inflammatory and anti-apoptosis properties of MaR 1 in NRVMs through the HMGB-1/NF-κB/NLRP-3 axis.

Conclusion: Our research suggests that MaR 1 pretreatment may alleviate cardiac IRI and suppress pyroptosis and apoptosis both in vivo and in vitro. MaR 1 inhibits pyroptosis through the SIRT1/HMGB-1/NF-κB/NLRP-3 axis. Therefore, MaR 1 may serve as a promising treatment for cardiac IRI.