Comparative study of the roles of cytokines and apoptosis in dilated and hypertrophic cardiomyopathies.
OBJECTIVE
In order to gain more insight into the pathogenesis of dilated and hypertrophic cardiomyopathies (DCM and HCM, respectively), we investigated the roles of certain cytokines that regulate apoptosis.


RESULTS
ELISA tests, performed to determine the plasma concentrations of tumour necrosis factor-alpha (TNF-alpha), the soluble Fas (sFas), interleukin-6 (IL-6) and the soluble IL-6 receptor (sIL-6R), revealed that DCM patients exhibit elevated concentrations of TNF-alpha, sFas, IL-6 and sIL-6R, while HCM patients have only high IL-6 and sIL-6R levels as compared with healthy individuals. Western blot analysis of the levels of TNF-alpha, IL-6, Bcl-2 and Bax proteins in myocardium samples demonstrated that DCM patients express increased levels of TNF-alpha, IL-6 and Bax, whereas HCM heart lysates display only elevated levels of Bcl-2. Annexin V binding assay of TNF-alpha-treated H9C2 cells indicated that the in vitro cytotoxicity of this cytokine involves apoptotosis and necrosis.


CONCLUSIONS
In accord with previous observations, our data indicate a strong activation of the pro-apoptotic TNF and Fas pathways in DCM patients, and an anti-apoptotic shift in HCM patients. These findings have a bearing on the pathogenesis of cardiomyopathies, since apoptosis may account for certain dysfunctions observed in DCM, while IL-6 may elicit the hypertrophy characteristic of HCM.
Buzás
Krisztina
K
Department of Medical Microbiology and Immunobiology; University of Szeged, Dóm tér 10, 6720 Szeged, Hungary.
Megyeri
Klára
K
Hõgye
Márta
M
Csanády
Miklós
M
Bogáts
Gábor
G
Mándi
Yvette
Y
D017304:Annexin A5 / Q000032:analysis / Q000096:biosynthesis; D017209:Apoptosis; D002311:Cardiomyopathy, Dilated / Q000097:blood* / Q000473:pathology; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000032:analysis / Q000096:biosynthesis; D002460:Cell Line; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis* / Q000097:blood; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis; D051856:Fanconi Anemia Complementation Group Proteins; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000032:analysis / Q000096:biosynthesis; D011237:Predictive Value of Tests; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000096:biosynthesis; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis / Q000097:blood*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis / Q000494:pharmacology; D051028:bcl-2-Associated X Protein
D017304:Annexin A5; C494826:BAX protein, human; D018797:Cell Cycle Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D051856:Fanconi Anemia Complementation Group Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein