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Am J Physiol Heart Circ Physiol 283: H829-H836, 2002; doi:10.1152/ajpheart.00416.2001
0363-6135/02 $5.00
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Vol. 283, Issue 2, H829-H836, August 2002

IRAK contributes to burn-triggered myocardial contractile dysfunction

James A. Thomas1,2, May F. Tsen1, D. Jean White3, and Jureta W. Horton3

1 Departments of Pediatrics, 2 Molecular Biology, and 3 Surgery, The University of Texas Southwestern Medical Center, Dallas, Texas 75390

Major burn injury causes myocardial contractile dysfunction, but the molecular basis of this physiological response is incompletely understood. Previous studies demonstrated a role for the interleukin-1 receptor-associated kinase (IRAK) in the cardiac response to acute lipopolysaccharide administration as well as congestive heart failure. In this study, we examined the contribution of IRAK to burn-mediated cardiac responses. After burn injury, hearts from wild-type and IRAK-deficient mice were compared for intracellular signaling pathway activation and contractile function. IRAK-deficient hearts showed impaired activation of kinases that function downstream of IRAK and were partially protected against burn-induced contractile dysfunction. The findings demonstrate that IRAK and the Toll/interleukin-1 pathways participate in the response to large body surface area burns that leads to impaired cardiac contractility.

burn injury; contractile function; signal transduction; transgenic animals


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