Protection against Myocardial Ischemia/Reperfusion Injury in TLR4-Deficient Mice Is Mediated through a Phosphoinositide 3-Kinase-Dependent Mechanism

摘要: TLRs play a critical role in the induction of innate and adaptive immunity. However, have also been reported to mediate pathophysiology organ damage following ischemia/reperfusion (I/R) injury. We that TLR4−/− mice show decreased myocardial injury I/R; however, protective mechanisms not elucidated. examined PI3K/Akt signaling pathway cardioprotection I/R age-matched wild-type (WT) were subjected ischemia for 45 min, followed by reperfusion 4 h. Pharmacologic inhibitors PI3K (wortmannin or LY294002) administered 1 h before I/R. Myocardial infarct size/area at risk was reduced 51.2% vs WT mice. Cardiac myocyte apoptosis increased blockade abrogated protection Specifically, heart 98% wortmannin 101% LY294002-treated mice, when compared with control These data indicate against is mediated through PI3K/Akt-dependent mechanism. The which are myocardium may involve phosphorylation/inactivation phosphatase tensin homolog deleted on chromosome 10 as well glycogen synthase kinase-3β. implicate immune pathways pathology acute suggest modulation TLR4/PI3K/Akt-dependent be viable strategy reducing