TLR4 deficiency in a mouse model of myocardial infarction significantly improved survival compared with wild-type mice (62% vs 23%; p < 0.0001) by attenuating left ventricular remodeling.
Absolute Event Rate: 62% vs 23%
p-value: p=< 0.0001
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 Cdelta 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.
Riad et al. (Thu,) conducted a other in Myocardial Infarction. TLR4 knockout vs. Wild-type (WT) mice was evaluated on Survival (p=< 0.0001). TLR4 deficiency in a mouse model of myocardial infarction significantly improved survival compared with wild-type mice (62% vs 23%; p < 0.0001) by attenuating left ventricular remodeling.