Comparative study of the roles of cytokines and apoptosis in dilated and hypertrophic cardiomyopathies

Abstract

Aims: 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.

Methods and 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.

Conclusion: 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.