Dynamic expression of the membrane attack complex (MAC) of the complement system in failing human myocardium.
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.
Oliveira
Guilherme H M
GH
Baylor College of Medicine, Houston, Texas; Methodist DeBakey Heart Center, Houston, Texas, USA.
Brann
Corinne N
CN
Becker
Katy
K
Thohan
Vinay
V
Koerner
Michael M
MM
Loebe
Mathias
M
Noon
George P
GP
Torre-Amione
Guillermo
G
D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D015153:Blotting, Western; D015938:Complement Membrane Attack Complex / Q000096:biosynthesis*; D018450:Disease Progression; D005260:Female; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012720:Severity of Illness Index
D015415:Biomarkers; D015938:Complement Membrane Attack Complex