The therapeutic effect of Nesfatin-1 on acute myocardial ischemia/reperfusion injury; a systematic review and meta-analysis

In recent years, various peptides have been introduced for the complementary treatment and management of post-reperfusion injuries. Nesfatin-1, a peptide secreted by the nervous system and peripheral tissues, modulates cardiac function, and plays an important role in the cardiovascular response to stress conditions. This systematic review and meta-analysis aims to investigate the preclinical evidence on the effect of Nesfatin-1 administration in the improvement of cardiac ischemia/reperfusion injury.

Online databases of PubMed, Embase, Web of Science, and Scopus were searched until November 2nd, 2022, for articles investigating the therapeutic effects of Nesfatin-1 administration on myocardial ischemia/reperfusion injury in preclinical models. Cardiac functions, infarct size, myocardial tissue fibrosis, inflammation, oxidative stress, apoptosis, necroptosis, and necrosis were chosen as outcomes. The results are reported as an overall standardized mean difference (SMD) and 95% confidence interval (CI).

Our results demonstrate that the administration of Nesfatin-1 improves cardiac parameters such as ejection fraction (SMD = 3.94, 95% CI: 0.30 to 7.58), heart rate (SMD = 3.30, 95% CI: 0.41 to 6.18), and negative dp/dt (SMD = 2.05, 95% CI: 0.60 to 3.50) and positive dp/dt (SMD = 2.78, 95% CI: 0.56 to 4.99). Nesfatin-1 was shown to significantly reduce myocardial infarct size (SMD = -4.32, 95% CI: -5.95 to -2.69 and fibrosis (SMD = -3.91, 95% CI: -5.67 to -2.15). Apoptotic score (SMD = -2.07, 95% CI: -3.51 to -0.63) and oxidative stress were also reduced subsequent to Nesfatin-1 administration. Nesfatin-1 was not shown to decrease inflammation, necroptosis, and necrosis.

In conclusion, we demonstrated that Nesfatin-1 could serve as a potential therapeutic agent in ameliorating the secondary damages during myocardial I/R injury. Nesfatin-1 administration can preserve cardiac function by reducing oxidative stress, apoptosis, and myocardial necrosis. However, much more studies are required to endorse further clinical translation of Nesfatin-1 to be utilized in the management of myocardial I/R injury.