BACKGROUND: Interluekin1 receptor-associated kinase-4 (IRAK4) plays an essential role in the innate immune system. The aim of this study was to investigate the role of IRAK4 in cardiac remodeling induced by pressure overload and elucidate the underlying mechanisms. METHODS: In vivo studies were performed using IRAK4 heterozygous knockout (HET) mice and wild type (WT) mice. Models of cardiac remodeling were induced by aortic banding (AB). Cardiac remodeling was evaluated by Echocardiography and histological analysis. RESULTS: IRAK4 was upregulated in hearts of dilated cardiomyopathy (DCM) patients and also pressure overload-induced mice hearts. IRAK4 HET mice exhibited exacerbated cardiac hypertrophy, dysfunction and fibrosis after 4 weeks of AB compared with that in WT mice. Furthermore, enhanced activation of the MEK-ERK1/2, p38 and NFκB pathways was found in IRAK4 HET mice compared to WT mice. CONCLUSION: Our results suggest that IRAK4 may play a crucial role in the development of cardiac remodeling via negative regulation of multiple signaling pathways.
BACKGROUND:Interluekin1 receptor-associated kinase-4 (IRAK4) plays an essential role in the innate immune system. The aim of this study was to investigate the role of IRAK4 in cardiac remodeling induced by pressure overload and elucidate the underlying mechanisms. METHODS: In vivo studies were performed using IRAK4 heterozygous knockout (HET) mice and wild type (WT) mice. Models of cardiac remodeling were induced by aortic banding (AB). Cardiac remodeling was evaluated by Echocardiography and histological analysis. RESULTS:IRAK4 was upregulated in hearts of dilated cardiomyopathy (DCM) patients and also pressure overload-induced mice hearts. IRAK4 HET mice exhibited exacerbated cardiac hypertrophy, dysfunction and fibrosis after 4 weeks of AB compared with that in WT mice. Furthermore, enhanced activation of the MEK-ERK1/2, p38 and NFκB pathways was found in IRAK4 HET mice compared to WT mice. CONCLUSION: Our results suggest that IRAK4 may play a crucial role in the development of cardiac remodeling via negative regulation of multiple signaling pathways.
Authors: F Charron; G Tsimiklis; M Arcand; L Robitaille; Q Liang; J D Molkentin; S Meloche; M Nemer Journal: Genes Dev Date: 2001-10-15 Impact factor: 11.361
Authors: Lei Wang; Yu-Lin Li; Cong-Cong Zhang; Wei Cui; Xia Wang; Yong Xia; Jie Du; Hui-Hua Li Journal: Cardiovasc Res Date: 2013-11-20 Impact factor: 10.787
Authors: Nobutaka Suzuki; Shinobu Suzuki; Gordon S Duncan; Douglas G Millar; Teiji Wada; Christine Mirtsos; Hidetoshi Takada; Andrew Wakeham; Annick Itie; Shyun Li; Josef M Penninger; Holger Wesche; Pamela S Ohashi; Tak W Mak; Wen-Chen Yeh Journal: Nature Date: 2002-03-31 Impact factor: 49.962