Dynamic Expression of the Membrane Attack Complex (MAC) of the Complement System in Failing Human Myocardium

Guilherme H.M. Oliveira, Corinne N. Brann, Katy Becker, Vinay Thohan, Michael M. Koerner, Mathias Loebe, George P. Noon, Guillermo Torre-Amione

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Inflammatory cytokine-mediated pathways are activated in heart failure and participate in the pathogenesis and progression of the disease. Another major response to inflammation is mediated through the complement system with the production of the membrane attack complex (MAC), a protein known to cause cell lysis and mediate apoptosis. It was postulated that the complement system is activated in patients with heart failure, and this study investigated whether hemodynamic conditions regulate this pathway. The expression of the MAC was assessed in myocardial biopsy samples of normal and failing hearts by immunohistochemistry and Western blot analysis. Myocardial samples from failing hearts were obtained before and after left ventricular assist device implantation. Immunohistochemical staining and Western blot analysis identified increased MAC expression in failing but not normal myocardium. After hemodynamic unloading with left ventricular assist device support, MAC expression returned to levels found in normal controls. In failing hearts, MAC expression did not differ between ischemic and nonischemic causes of heart failure. In conclusion, increased MAC expression in failing human hearts indicates that the complement system is activated in the heart failure milieu. Its removal after hemodynamic normalization is evidence of dynamic regulation, suggesting a pathogenic role for the MAC. These findings identify the complement system as part of a novel pathophysiologic path in heart failure that can potentially be targeted by future therapy.

Original languageEnglish (US)
Pages (from-to)1626-1629
Number of pages4
JournalAmerican Journal of Cardiology
Volume97
Issue number11
DOIs
StatePublished - Jun 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Oliveira, G. H. M., Brann, C. N., Becker, K., Thohan, V., Koerner, M. M., Loebe, M., Noon, G. P., & Torre-Amione, G. (2006). Dynamic Expression of the Membrane Attack Complex (MAC) of the Complement System in Failing Human Myocardium. American Journal of Cardiology, 97(11), 1626-1629. https://doi.org/10.1016/j.amjcard.2005.12.056