Recombinant human IL-37 attenuated isoproterenol-induced cardiac hypertrophy in vivo and in vitro by reducing oxidative stress, inflammation, and apoptosis via JAK2/STAT3 signaling inactivation.
Does IL-37 reduce cardiac hypertrophy, inflammation, and oxidative stress in ISO-induced models?
IL-37 attenuates isoproterenol-induced cardiac hypertrophy by reducing oxidative stress and inflammation via inactivation of the JAK2/STAT3 signaling pathway in preclinical models.
BACKGROUND: Inflammation and oxidative stress have drawn more and more interest in the realm of cardiovascular disease. In many different disorders, IL-37 acts as an anti-inflammatory and suppressor of inflammation. This study aimed to investigate whether IL-37 could alleviate cardiac hypertrophy by reducing inflammation and oxidative stress. METHODS: In vivo, a cardiac hypertrophy model was induced by 14 d of daily isoproterenol (ISO, 30 mg/kg/d) injection, followed by weeks of treatment with recombinant human IL-37 (1000 ng/animal), administered three times weekly. Assessments concentrated on markers of inflammation and oxidative stress, apoptosis, myocardial disease, and cardiac shape and function. In vitro, neonatal rat cardiomyocytes (NRCMs) were subjected to ISO (10 µM) to establish a cardiomyocytes hypertrophy model. Subsequent IL-37 treatment (100 ng/ml) was applied to determine its cardioprotective efficacy and to elucidate further the underlying mechanisms involved. RESULTS: Significant cardioprotective benefits of IL-37 were seen (in vitro as well as in vivo), primarily through the reduction of oxidative stress, inflammation, apoptosis, and heart hypertrophy markers. Furthermore, IL-37 treatment was associated with a decrease in JAK2 and STAT3 phosphorylation. It is interesting to note that WP1066, a JAK2/STAT3 inhibitor, exhibited antioxidant and anti-inflammatory properties comparable to IL-37, as well as synergistic effects when mixed with the latter. CONCLUSION: ISO-induced cardiac hypertrophy is lessened by IL-37 through the reduction of oxidative stress and inflammation. Additionally, the effects of IL-37 are closely related to inactivation of the JAK2/STAT3 signaling pathway. It is anticipated that IL-37 will one day be used to treat cardiovascular illnesses such as heart hypertrophy.
Guo et al. (Tue,) conducted a other in Isoproterenol-induced cardiac hypertrophy. Recombinant human IL-37 was evaluated on Cardiac hypertrophy, oxidative stress, inflammation, and apoptosis markers. Recombinant human IL-37 attenuated isoproterenol-induced cardiac hypertrophy in vivo and in vitro by reducing oxidative stress, inflammation, and apoptosis via JAK2/STAT3 signaling inactivation.