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This Article Full Text Full Text (PDF) All Versions of this Article: 292/1/H503    most recent 00642.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Sakata, Y. Articles by Mann, D. L. Search for Related Content PubMed PubMed Citation Articles by Sakata, Y. Articles by Mann, D. L.

Toll-like receptor 2 modulates left ventricular function following ischemia-reperfusion injury

¹Department of Medicine, Winters Center for Heart Failure Research, ²Texas Heart Institute at Saint Luke's Episcopal Hospital, ³Section of Infectious Diseases, Department of Pediatrics, Baylor College of Medicine, and Texas Children's Hospital, Houston, Texas; ⁴Laboratory of Biomedical Science, North Shore University Hospital, New York University School of Medicine, Manhasset, New York; and ⁵Department of Host Defense, Osaka University, Osaka, Japan

Submitted 15 June 2006 ; accepted in final form 28 August 2006

Production of proinflammatory cytokines contributes to cardiac dysfunction during ischemia-reperfusion. The principal mechanism responsible for the induction of this innate stress response during periods of myocardial ischemia-reperfusion remains unknown. Toll-like receptor 2 (TLR2) is a highly conserved pattern recognition receptor that has been implicated in the innate immune response to a variety of pathogens. However, TLR2 may also mediate inflammation in response to noninfectious injury. We therefore hypothesized that TLR2 is essential for modulating myocardial inflammation and left ventricular (LV) function during ischemia-reperfusion injury. Susceptibility to myocardial ischemia-reperfusion injury following ischemia-reperfusion was determined in Langendorff-perfused hearts isolated from wild-type mice and mice deficient in TLR2 (TLR2D) and Toll interleukin receptor domain-containing adaptor protein. After ischemia-reperfusion, contractile performance was significantly impaired in hearts from wild-type mice as demonstrated by a lower recovery of LV developed pressure relative to TLR2D hearts. Creatinine kinase levels were similar in both groups after reperfusion. Contractile dysfunction in wild-type hearts was associated with elevated cardiac levels of TNF and IL-1. Ischemia-reperfusion-induced LV dysfunction was reversed by treatment with the recombinant TNF blocking protein etanercept. These studies show for the first time that TLR2 signaling importantly contributes to the LV dysfunction that occurs following ischemia-reperfusion. Thus disruption of TLR2-mediated signaling may be helpful to induce immediate or delayed myocardial protection from ischemia-reperfusion injury.

inflammation; innate immunity; myocardial function

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