Toll-like receptor 4 deficiency: Smaller infarcts, but nogain in functionReport as inadecuate

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BMC Physiology

, 7:5

First Online: 25 June 2007Received: 23 December 2006Accepted: 25 June 2007


BackgoundIt has been reported that Toll-like receptor 4 TLR4 deficiency reduces infarct size after myocardial ischemia-reperfusion MI-R. However, measurement of MI-R injury was limited and did not include cardiac function . In a chronic closed-chest model we assessed whether cardiac function is preserved in TLR4-deficient mice C3H-HeJ following MI-R, and whether myocardial and systemic cytokine expression differed compared to wild type WT.

ResultsInfarct size IS in C3H-HeJ assessed by TTC staining after 60 min ischemia and 24h reperfusion was significantly smaller than in WT. Despite a smaller infarct size, echocardiography showed no functional difference between C3H-HeJ and WT. Left-ventricular developed pressure measured with a left-ventricular catheter was lower in C3H-HeJ 63.0 ± 4.2 mmHg vs. 77.9 ± 1.7 mmHg in WT, p < 0.05. Serum cytokine levels and myocardial IL-6 were higher in WT than in C3H-HeJ p < 0.05. C3H-HeJ MI-R showed increased myocardial IL-1β and IL-6 expression compared to their respective shams p < 0.05, indicating TLR4-independent cytokine activation due to MI-R.

ConclusionThese results demonstrate that, although a mutant TLR4 signaling cascade reduces myocardial IS and serum cytokine levels, it does not preserve myocardial function . The change in inflammatory response, secondary to a non-functional TLR-4 receptor, may contribute to the observed dichotomy between infarct size and function in the TLR-4 mutant mouse.

Electronic supplementary materialThe online version of this article doi:10.1186-1472-6793-7-5 contains supplementary material, which is available to authorized users.

Se-Chan Kim, Alexander Ghanem contributed equally to this work.

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Author: Se-Chan Kim - Alexander Ghanem - Heidi Stapel - Klaus Tiemann - Pascal Knuefermann - Andreas Hoeft - Rainer Meyer - Christi


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