Toll-like receptor 4 deficiency: Smaller infarcts, but nogain in function

Se Chan Kim, Alexander Ghanem, Heidi Stapel, Klaus Tiemann, Pascal Knuefermann, Andreas Hoeft, Rainer Meyer, Christian Grohé, Anne A Knowlton, Georg Baumgarten

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Abstract

Backgound. It 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). Results. Infarct 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. Conclusion. These 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.

Original languageEnglish (US)
Article number5
JournalBMC Physiology
Volume7
DOIs
StatePublished - 2007

ASJC Scopus subject areas

  • Medicine(all)

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    Kim, S. C., Ghanem, A., Stapel, H., Tiemann, K., Knuefermann, P., Hoeft, A., Meyer, R., Grohé, C., Knowlton, A. A., & Baumgarten, G. (2007). Toll-like receptor 4 deficiency: Smaller infarcts, but nogain in function. BMC Physiology, 7, [5]. https://doi.org/10.1186/1472-6793-7-5