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Volume 11 Supplement 4

Sepsis 2007

Reduction of gap junction proteins and intercalated disc structural remodeling in the hearts of mice submitted to sepsis

Background

Cardiac dysfunction due to impaired myocardial contractility has been recognized as an important factor contributing to high mortality in septic patients. A recent study from our laboratory gives support to the opinion that myocardial structural change, classifiable as inflammatory cardiomyopathy, could be responsible for sepsis-induced myocardial dysfunction. The present study describes intercalated disc remodeling under both protein expression and structural features in experimental severe sepsis induced by cecal ligation and puncture (CLP) in mice.

Materials and methods

Male C57Bl/6 mice weighing between 18 and 22 g were subjected to sham-operated surgery, moderate or severe septic injury, both induced by CLP.

Results

Severe septic injury was accompanied by large number of bacteria in the peritoneal cavity and blood, high levels of TNFα and MIP-1α in the septic focus and serum, marked hypotension, and high mortality rate. Western blot analysis and immunofluorescence showed a marked decrease of key gap and adherens junction proteins (connexin43 and N-cadherin, respectively) in mice subjected to severe septic injury. These changes may result in the loss of intercalated disc structural integrity characterized in the electron microscopic study by partial separation or dehiscence of the gap junction and adherens junctions.

Conclusion

Our data provide important insight regarding the alterations in intercalated disc components resulting from severe septic injury. The intercalated disc remodeling under both protein expression and structural features in experimental severe sepsis induced by CLP may be partly responsible for myocardial depression in sepsis/septic shock. The abnormal parameters may emerge as therapeutic targets and their modulation might provide beneficial effects on future cardiovascular outcomes and mortality in sepsis.

Acknowledgements

Supported by FAPESP (04/01777-0 and 04/14578-5) and FAEPA.

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Celes, M.R.N., Torrez-Dueñas, D., Alves-Filho, J.C. et al. Reduction of gap junction proteins and intercalated disc structural remodeling in the hearts of mice submitted to sepsis. Crit Care 11, P45 (2007). https://doi.org/10.1186/cc6024

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Keywords

  • Junction Protein
  • Adherens Junction
  • Structural Remodel
  • Cecal Ligation
  • Intercalate Disc