Attenuation of Cardiac Hypertrophy by Inhibiting Both mTOR and NFκB Activation in Vivo
Document Type
Article
Publication Date
12-15-2005
Description
A role for the PI3K/Akt/mTOR pathway in cardiac hypertrophy has been well documented. We reported that NFκB activation is needed for cardiac hypertrophy in vivo. To investigate whether both NFκB activation and PI3K/Akt/mTOR signaling participate in the development of cardiac hypertrophy, two models of cardiac hypertrophy, namely, induction in caAkt-transgenic mice and by aortic banding in mice, were employed. Rapamycin (2 mg/kg/daily), an inhibitor of the mammalian target of rapamycin, and the antioxidant pyrrolidine dithiocarbamate (PDTC; 120 mg/kg/daily), which can inhibit NFκB activation, were administered to caAkt mice at 8 weeks of age for 2 weeks. Both rapamycin and PDTC were also administered to the mice immediately after aortic banding for 2 weeks. Administration of either rapamycin or PDTC separately or together to caAkt mice reduced the ratio of heart weight/body weight by 21.54, 32.68, and 42.07% compared with untreated caAkt mice. PDTC administration significantly reduced cardiac NFκB activation by 46.67% and rapamycin significantly decreased the levels of p70S6K by 34.20% compared with untreated caAkt mice. Similar results were observed in aortic-banding-induced cardiac hypertrophy in mice. Our results suggest that both NFκB activation and the PI3K/Akt signaling pathway participate in the development of cardiac hypertrophy in vivo.
Citation Information
Ha, Tuanzhu; Li, Yuehua; Gao, Xiang; McMullen, Julie R.; Shioi, Tetsuo; Izumo, Seigo; Kelley, Jim L.; Zhao, Aiqiu; Haddad, Georges E.; Williams, David L.; Browder, I. William; Kao, Race L.; and Li, Chuanfu. 2005. Attenuation of Cardiac Hypertrophy by Inhibiting Both mTOR and NFκB Activation in Vivo. Free Radical Biology and Medicine. Vol.39(12). 1570-1580. https://doi.org/10.1016/j.freeradbiomed.2005.08.002 PMID: 16298682 ISSN: 0891-5849