HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Riad, A. Articles by Tschöpe, C. PubMed PubMed Citation Articles by Riad, A. Articles by Tschöpe, C.

Toll-Like Receptor-4 Modulates Survival by Induction of Left Ventricular Remodeling after Myocardial Infarction in Mice¹

Alexander Riad^*, Sebastian Jäger^*, Meike Sobirey^*, Felicitas Escher^*, Aymaru Yaulema-Riss^*, Dirk Westermann^*, Aysun Karatas, Markus M. Heimesaat, Stefan Bereswill, Duska Dragun, Matthias Pauschinger^*, Heinz P. Schultheiss^* and Carsten Tschöpe^2,*

^* Department of Cardiology and Pneumology and Department of Microbiology, Campus Benjamin Franklin and Department of Nephrology and Intensive Care Medicine, Campus Virchow Clinic and Center for Cardiovascular Research, Charité University Medicine, Berlin, Germany

Left ventricular (LV) remodeling is known to contribute to morbidity and mortality after myocardial infarction (MI). Because LV remodeling is strongly associated with an inflammatory response, we investigated whether or not TLR-4 influences LV remodeling and survival in a mice model of MI. Six days after MI induction, TLR4 knockout (KO)-MI mice showed improved LV function 32 and reduced LV remodeling as indexed by reduced levels of atrial natriuretic factor and total collagen as well as by a reduced heart weight to body weight ratio when compared with WT-MI mice. This was associated with a reduction of protein levels of the intracellular TLR4 adapter protein MyD88 and enhanced protein expression of the anti-hypertrophic JNK in KO-MI mice when compared with wild-type (WT)-MI mice. In contrast, protein activation of the pro-hypertrophic kinases protein kinase C and p42/44 were not regulated in KO-MI mice when compared with WT-MI mice. Improved LV function, reduced cardiac remodeling, and suppressed intracellular TLR4 signaling in KO-MI mice were associated with significantly improved survival compared with WT-MI mice (62 vs 23%; p < 0.0001). TLR4 deficiency led to improved survival after MI mediated by attenuated left ventricular remodeling.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a grant from the Deutsche Forschungsgesellschaft (TR-SFB 19, project Z3 and B2) to C.T.

² Address correspondence and reprint requests to Dr. Carsten Tschöpe, Department of Cardiology and Pneumology, Charité-University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. E-mail address: carsten.tschoepe{at}charite.de

³ Abbreviations used in this paper: MI, myocardial infarction; ANF, atrial natriuretic factor; dP/dt_max, maximal rate of LV pressure rise (mm HG/s); dP/dt_min, minimal rate of LV pressure fall (mm HG/s); KO, knockout (TLR4-deficient mice); LV, left ventricular; LVEDP, LV end diastolic pressure; LVP, LV peak systolic pressure; p (prefix), phosphorylated; PKC, protein kinase C; WT, wild type.