Neuregulin-4 alleviated isoproterenol-induced cardiac dysfunction, hypertrophy, fibrosis, and apoptosis in mice by regulating the AMPK/NF-κB signaling pathway.
Neuregulin-4 protects against isoproterenol-induced cardiac remodeling, inflammation, and apoptosis in mice via the AMPK/NF-κB pathway, suggesting a potential therapeutic target for heart failure.
Cardiac remodeling refers to the abnormal changes in cardiac structure and function caused by various pathological conditions. It is an inevitable pathological process in the occurrence and development of heart failure and is related to a variety of cardiovascular diseases. Inflammation and apoptosis are critical pathological processes involved in cardiac remodeling. Neuregulin 4 (Nrg 4) is an adipokine produced primarily by brown adipose tissue that may play a protective role in a variety of inflammatory diseases. The aim of this study was to investigate whether Nrg4 can delay the progression of cardiac remodeling by regulating AMPK/NF-κB pathway, inhibiting inflammation and apoptosis. In our study, we established a model of cardiac remodeling in mice after 14 days of isoproterenol (ISO) intervention, and then gave Nrg4 treatment for another 4 weeks. The cardiac function, the degree of myocardial hypertrophy and myocardial fibrosis of the mice were observed. At the same time, the levels of apoptosis-related proteins (Bax,Bcl-2,Caspase-3), IL-6,IL-Iβ and TNF-α, as well as the activation level of AMPK/NF-κB signaling pathway were evaluated.Nrg4 alleviated ISO-induced cardiac dysfunction, cardiac hypertrophy and fibrosis in mice. Nrg4 also attenuated ISO-induced apoptosis and reduces levels of inflammatory factors to protect ISO-induced myocardial damage. At the same time, the effect of Nrg4 on AMPK/NF-κB pathway was measured in vivo and in vitro. The administration of an AMPK inhibitor was found to reverse the anti-hypertrophy, anti-inflammatory, and anti-apoptotic effects of Nrg4. Our findings suggest that Nrg4 may play a protective role in cardiac remodeling by inhibiting inflammation and apoptosis via AMPK/NF-κB pathway.
Wei et al. (Wed,) conducted a other in Isoproterenol (ISO)-induced cardiac remodeling. Neuregulin 4 (Nrg4) vs. Isoproterenol alone (implied) was evaluated on Cardiac function, myocardial hypertrophy, myocardial fibrosis, apoptosis, and inflammation. Neuregulin-4 alleviated isoproterenol-induced cardiac dysfunction, hypertrophy, fibrosis, and apoptosis in mice by regulating the AMPK/NF-κB signaling pathway.