Rapamycin Attenuated Cardiac Hypertrophy Induced by Isoproterenol and Maintained Energy Homeostasis via Inhibiting NF-κB Activation

Abstract

Rapamycin, also known as sirolimus, is an immunosuppressant drug used to prevent rejection organ (especially kidney) transplantation. However, little is known about the role of Rapa in cardiac hypertrophy induced by isoproterenol and its underlying mechanism. In this study, Rapa was administrated intraperitoneally for one week after the rat model of cardiac hypertrophy induced by isoproterenol established. Rapa was demonstrated to attenuate isoproterenol-induced cardiac hypertrophy, maintain the structure integrity and functional performance of mitochondria, and upregulate genes related to fatty acid metabolism in hypertrophied hearts. To further study the implication of NF-κB in the protective role of Rapa, cardiomyocytes were pretreated with TNF-α or transfected with siRNA against NF-κB/p65 subunit. It was revealed that the upregulation of extracellular circulating proinflammatory cytokines induced by isoproterenol was able to be reversed by Rapa, which was dependent on NF-κB pathway. Furthermore, the regression of cardiac hypertrophy and maintaining energy homeostasis by Rapa in cardiomyocytes may be attributed to the inactivation of NF-κB. Our results shed new light on mechanisms underlying the protective role of Rapa against cardiac hypertrophy induced by isoproterenol, suggesting that blocking proinflammatory response by Rapa might contribute to the maintenance of energy homeostasis during the progression of cardiac hypertrophy.

Deletion of MLIP (Muscle-enriched A-type Lamin-interacting Protein) Leads to Cardiac Hyperactivation of Akt/Mammalian Target of Rapamycin (mTOR) and Impaired Cardiac Adaptation

“…As previously reported (27)(28)(29), ISO treatment resulted in increased activity of mTOR, as evidenced by the increase in phospho-mTOR to total mTOR ratio in ISOtreated Mlip ϩ/ϩ when compared with saline-treated Mlip ϩ/ϩ hearts (Fig. 6F).…”

Puerarin prevents cardiac hypertrophy induced by pressure overload through activation of autophagy

“…As an activator of autophagy, rapamycin has been shown to be able to prevent cardiac hypertrophy in animals subjected to thyroid hormone or isoprenaline treatment, and even to reverse stressinduced cardiac hypertrophy, leading to improved cardiac function [16,17]. Similar to previous data, the results of the present study using rapamycin treatment as a positive control in AB rats showed reproducible protective effects, including prevention of cardiac hypertrophy progression, retardation of remodeling, and inhibition of cardiomyocyte apoptosis, accompanied by activation of autophagy.…”

Dimethyl fumarate interferes with MyD88-dependent toll-like receptor signalling pathway in isoproterenol-induced cardiac hypertrophy model

“…Then, the hearts were rapidly excised, washed with ice-cold phosphate-buffered saline, dried and weighed to calculate heart-to-body weight (HW/BW) ratio. [19,22] The hearts were homogenized in phosphate-buffered saline, and supernatants were stored at À80°C for biochemical assays. Three hearts from each group were fixed in 10% neutral-buffered formal saline for histopathological study.…”