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Decreased myocardial expression of dystrophin and titin mRNA and protein in dilated cardiomyopathy: possibly an adverse effect of TNF-alpha.

Authors: Ahmad, S  Rai, TS  Khullar, M  Bahl, A  Saikia, UN  Thungapathra, M  Kumar, RM  Mahajan, R  Talwar, KK 
Citation: Ahmad S, etal., J Clin Immunol. 2010 Jul;30(4):520-30. Epub 2010 Apr 7.
Pubmed: (View Article at PubMed) PMID:20373002
DOI: Full-text: DOI:10.1007/s10875-010-9388-3

BACKGROUND AND AIMS: While the molecular basis of dilated cardiomyopathy (DCM) remains uncertain, concrete evidence is emerging that sarcomeric and cytoskeleton gene expression of myocardium isolated from failing versus non-failing patients differ dramatically. The central aim to this work was to find out the possible role of dystrophin and titin along with the TNF-alpha in the pathogenesis of cardiomyopathy. PATIENTS AND METHODS: mRNA levels and protein expression of a cytoskeletal protein, dystrophin and a sarcomeric protein, titin in endomyocardial biopsies of DCM patients were examined using RT-PCR and immunohistochemistry, respectively. Further, we examined the effect of TNF-alpha on myocardial expression of titin and dystrophin in vitro in rat cardiac myoblast cell line (H9c2). RESULTS: We observed significantly decreased mRNA and protein levels of dystrophin and titin in endomyocardial biopsy of DCM patients as compared to control group. The decreased levels of these proteins correlated with the severity of the disease. Plasma levels of both TNF-alpha and its soluble receptors TNFR1 and TNFR2 were found to be significantly higher in patients as compared to control group. Treatment of H9c2 cells with TNF-alpha resulted in a dose- and time-dependent decrease in mRNA levels of dystrophin and titin. Pretreatment of these cells with MG132, an inhibitor of nuclear factor kappa B (NF-kappaB) pathway, abolished TNF-alpha-induced reduction in mRNA levels of dystrophin and titin. CONCLUSION: Our results suggest that reduced expression of dystrophin and titin is associated with the pathophysiology of DCM, and TNF-alpha may modulate the expression of these proteins via NF-kappaB pathway.


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CRRD Object Information
CRRD ID: 6771365
Created: 2012-07-30
Species: All species
Last Modified: 2012-07-30
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.