Journal
CARDIOVASCULAR RESEARCH
Volume 57, Issue 3, Pages 749-756Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0008-6363(02)00723-X
Keywords
cytokines; immunology; infarction; remodeling
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Objective: Innate immune response proteins such as inflammatory cytokines, inducible nitric oxide synthase, and toll like receptors are implicated in myocardial depression and left ventricular (LV) remodeling after myocardial infarction (MI), Although all these innate immunity proteins share the downstream activation of the transcription factor NF-kappaB (nuclear factor kappa 13) and activator protein I (AP-1). the involvement of NF-kappaB and AP-1 in LV remodeling has not been demonstrated so far. Methods and results: Nuclear translocation of NF-kappaB and AP-1 was studied by electrophoretic mobility shift assays and ELISA 10 weeks after large experimental M1 in rats, the chronic phase of LV remodeling. In the non-infarcted myocardium of MI rats, NF-kappaB and AP-1 were significantly activated (2.5-fold) as compared to sham-operated animals. Immunohistochemistry demonstrated NF-kappaB activation mainly in cardiac myocytes. Treatment with the ACE (angiotensin converting enzyme) inhibitor trandolapril led to a further 2-fold increase ill the activation of NF-kappaB and AP-1 when compared to placebo-treated animals with the same MI size (P<0.001). Human failing hearts explanted at the time of heart transplantation exhibited marked nuclear translocation of NF-kappaB in cardiac myocytes when compared to control hearts. NF-kappaB as well as AP-1 were both significantly activated in congestive heart failure due to ischermic or dilated cardiomyopathy. Conclusion: In experimental and human heart failure, both NF-kappaB and AP-1 are chronically activated in cardiac myocytes. These findings suggest an important involvement of NF-kappaB and AP-1 in the cardiac remodeling process. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.
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