A possible role for complement in the pathogenesis of chronic chagasic cardiomyopathy.
The membrane attack complex (MAC) of complement participates in several inflammatory and proliferative processes by releasing pro-inflammatory cytokines and growth factors from target cells. Chronic Chagasic cardiomyopathy (CCH) is a parasitic dilated cardiopathy, characterized by severe fibrosis and inflammation, which differs from idiopathic dilated cardiomyopathy (DCM). Trypanosoma cruzi, the pathogenic organism of CCH, is a strong complement activator and can also induce alternative pathway activation by mammalian cells. This study explored whether the myocardium in CCH patients has increased MAC deposition, an expression of complement activation, compared to DCM patients. MAC was semi-quantified in endomyocardial human samples (29 CCH subjects, 18 DCM subjects, and four controls) by immunohistochemistry. MAC was present in the sarcolemma of 38% of CCH, 5.5% of DCM (p<0.02), and 0% of controls, and in interstitial inflammatory cells of CCH. No difference was observed in the expression of the complement regulatory protein CD59, indicating that increased MAC deposition is likely to be the result of complement activation rather than decreased protection. It is proposed that the increased MAC deposition found in CCH, but not in DCM or controls, may help to explain the diffuse myocardial fibrosis and inflammation characteristic of the disease.
Aiello
Vera Demarchi
VD
Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil. anpvera@incor.usp.br
Reis
Márcia Martins
MM
Benvenuti
Luiz Alberto
LA
Higuchi
Maria de Lourdes
Mde L
Ramires
José Antonio Franchini
JA
Halperin
José A
JA
D000328:Adult; D018957:CD59 Antigens / Q000032:analysis; D002311:Cardiomyopathy, Dilated / Q000276:immunology; D002598:Chagas Cardiomyopathy / Q000276:immunology*; D002908:Chronic Disease; D003167:Complement Activation; D015938:Complement Membrane Attack Complex / Q000032:analysis*; D003331:Coronary Vessels / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D009206:Myocardium / Q000276:immunology*; D012189:Retrospective Studies; D012508:Sarcolemma / Q000276:immunology
D018957:CD59 Antigens; D015938:Complement Membrane Attack Complex