IRAK4 deficiency promotes cardiac remodeling induced by pressure overload.
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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.
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Où se fait cette recherche
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Wuhan University Department of Cardiology pays non établi dans la noticeUniversité ou école supérieure
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Renmin Hospital of Wuhan University pays non établi dans la noticeÉtablissement de santé
Department of Cardiology — Wuhan University et Renmin Hospital of Wuhan University.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.