Immune cell toll-like receptor 4 is required for cardiac myocyte impairment during endotoxemia

Samantha A. Tavener, Elizabeth M. Long, Stephen M. Robbins, Krista M. McRae, Holly Van Remmen, Paul Kubes

Research output: Contribution to journalArticlepeer-review

123 Scopus citations


The aim of this study was to investigate the importance of Toll-like receptor 4 (TLR4) signaling on cardiac myocytes versus immune cells in lipopolysaccharide (LPS)-induced cardiac dysfunction. Cardiac myocytes isolated from LPS-treated C57B1/6 mice showed reduced shortening and calcium transients as compared with myocytes from untreated mice. In addition, LPS-treated C57B1/6 mice showed impaired cardiac mitochondrial function, including reduced respiration and reduced time of induction of permeability transition. All of the aforementioned cardiac dysfunction was dependent on TLR4, because LPS-treated TLR4-deficient mice did not have reduced myocyte shortening or mitochondrial dysfunction. To evaluate the role of cardiac myocyte versus leukocyte TLR4, LPS was injected into chimeric mice with TLR4-positive leukocytes and TLR4-deficient myocytes. These mice showed reduced myocyte shortening in response to LPS. Myocytes from chimeric mice with TLR4-deficient leukocytes and TLR4-positive myocytes had no response to LPS. In addition, isolated myocytes from C57B1/6 mice subsequently treated with LPS and serum for various times did not have reduced shortening, despite the presence of TLR4 mRNA and protein, as determined by reverse-transcription polymerase chain reaction and fluorescent-activated cell sorting. In fact, cardiac myocytes had equivalent amounts of TLR4 as endothelium; however, only the latter is responsive to LPS. Furthermore, signaling pathways downstream of TLR4 were not activated during direct LPS treatment of myocytes. In conclusion, TLR4 on leukocytes, and not on cardiac myocytes, is important for cardiac myocyte impairment during endotoxemia.

Original languageEnglish (US)
Pages (from-to)700-707
Number of pages8
JournalCirculation research
Issue number7
StatePublished - Oct 1 2004


  • Contractility
  • Heart
  • Inflammation
  • Neutrophils
  • Sepsis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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