The TIR/BB-loop mimetic AS-1 prevents cardiac hypertrophy by inhibiting IL-1R-mediated MyD88-dependent signaling
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Yun Zhu Ting Li Juan Song Chunyang Liu Yulong Hu Lingli Que Tuanzhu Ha Jim Kelley Qi Chen Chuanfu Li Yuehua Li
- چاپ و سال / کشور: 2011
Description
Activation of NF-jB contributes to cardiac hypertrophy and the interleukin-1 receptor (IL-1R)-mediated MyD88-dependent signaling pathway predominately activates NF-jB. Recent studies have shown that the TIR/ BB-Loop mimetic (AS-1) disrupted the interaction of MyD88 with the IL-1R, resulting in blunting of NF-jB activation. We have examined the effects of AS-1 on the IL- 1b-induced hypertrophic response using cultured neonatal cardiac myocytes in vitro and transverse aortic constriction (TAC) pressure overload-induced cardiac hypertrophy in vivo. Neonatal cardiac myocytes were treated with AS-1 15 min prior to IL-1b stimulation for 24 h. AS-1 treatment significantly attenuated IL-1b-induced hypertrophic responses of cardiac myocytes. In vivo experiments showed that AS-1 administration prevented cardiac hypertrophy and dysfunction induced by pressure overload. AS-1 administration disrupted the interaction of IL-1R with MyD88 in the pressure overloaded hearts and prevented activation of NF-jB. In addition, AS-1 prevented increases in activation of the MAPK pathway (p38 and p-ERK) in TAC-induced hypertrophic hearts. Our data suggest that the IL-1R-mediated MyD88-dependent signaling pathway plays a role in the development of cardiac hypertrophy and AS-1 attenuation of cardiac hypertrophy is mediated by blocking the interaction between IL-1R and MyD88, resulting in decreased NF-jB binding activity and decreased MAPK activation.
Basic Res Cardiol (2011) 106:787–799 Received: 26 August 2010 / Revised: 29 March 2011 / Accepted: 15 April 2011 / Published online: 1 May 2011
