Escherichia coli LPS-induced LV dysfunction: Role of toll-like receptor-4 in the adult heart

Shintaro Nemoto, Jesus G. Vallejo, Pascal Knuefermann, Arunima Misra, Gilberto Defreitas, Blase A. Carabello, Douglas L. Mann

Research output: Contribution to journalArticlepeer-review

162 Scopus citations


The precise molecular mechanisms responsible for sepsis-induced myocardial dysfunction remain undefined. Toll-like receptor-4 (TLR-4) engages lipopolysaccharide (LPS) and activates signaling pathways leading to the expression of proinflammatory cytokines implicated in myocardial dysfunction. We determined whether TLR-4 was necessary for LPS-induced myocardial dysfunction in vivo. The effects of LPS on left ventricular (LV) function were studied in mice with defective TLR-4 signaling (C3H/HeJ, TLR-4 deficient) and wild-type mice (C3HeB/FeJ). Mice (n = 5/group) were injected with LPS or diluent, and LV function was examined by using two-dimensional echocardiography and conductance catheters. LPS significantly decreased all indexes of LV function in wild-type mice when compared with controls; LV function was not depressed in the LPS-treated TLR-4-deficient mice relative to controls. LPS increased myocardial nitric oxide synthase-2 expression and cGMP only in wild-type mice. This study suggests that TLR-4 mediates the LV dysfunction that occurs in LPS-induced shock. Therefore, TLR-4 might be a therapeutic target for attenuating the effects of LPS on the heart.

Original languageEnglish
Pages (from-to)H2316-H2323
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number6 51-6
StatePublished - 2002


  • Endotoxic shock
  • Innate immunity
  • Myocardial depression
  • Proinflammatory cytokine


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