Soluble TNF receptors prevent apoptosis in infiltrating cells and promote ventricular rupture and remodeling after myocardial infarction
Y Monden, T Kubota, T Tsutsumi, T Inoue… - Cardiovascular …, 2007 - academic.oup.com
Y Monden, T Kubota, T Tsutsumi, T Inoue, S Kawano, N Kawamura, T Ide, K Egashira…
Cardiovascular research, 2007•academic.oup.comObjective: Tumor necrosis factor (TNF)-α induced in damaged myocardium has been
considered to be cardiotoxic. However, the negative results of RENEWAL and ATTACH
prompt us to reconsider the role of TNF-α in cardiovascular diseases. The present study
aimed to evaluate the effects of soluble TNF receptor treatment on myocardial infarction (MI).
Methods: An adenovirus encoding a 55-kDa TNF receptor-IgG fusion protein (AdTNFR1)
was used to neutralize TNF-α, and an adenovirus encoding LacZ (AdLacZ) served as …
considered to be cardiotoxic. However, the negative results of RENEWAL and ATTACH
prompt us to reconsider the role of TNF-α in cardiovascular diseases. The present study
aimed to evaluate the effects of soluble TNF receptor treatment on myocardial infarction (MI).
Methods: An adenovirus encoding a 55-kDa TNF receptor-IgG fusion protein (AdTNFR1)
was used to neutralize TNF-α, and an adenovirus encoding LacZ (AdLacZ) served as …
Abstract
Objective: Tumor necrosis factor (TNF)-α induced in damaged myocardium has been considered to be cardiotoxic. However, the negative results of RENEWAL and ATTACH prompt us to reconsider the role of TNF-α in cardiovascular diseases. The present study aimed to evaluate the effects of soluble TNF receptor treatment on myocardial infarction (MI).
Methods: An adenovirus encoding a 55-kDa TNF receptor-IgG fusion protein (AdTNFR1) was used to neutralize TNF-α, and an adenovirus encoding LacZ (AdLacZ) served as control. In the pre-MI treatment protocol, mice were given an intravenous injection of AdTNFR1 or AdLacZ 1 week before left coronary artery ligation to induce MI. In the post-MI treatment protocol, mice were treated with AdTNFR1 or AdLacZ 1 week after left coronary ligation.
Results: Treatment with AdTNFR1 neutralized bioactivity of TNF-α that was activated after MI and prevented apoptosis of infiltrating cells in infarct myocardium. However, pre-MI treatment with AdTNFR1 promoted ventricular rupture by reducing fibrosis with further activation of matrix metalloproteinase (MMP)-9. Post-MI treatment with AdTNFR1 exacerbated ventricular dysfunction and remodeling, with enhanced fibrosis of non-infarct myocardium with further MMP-2 activation.
Conclusions: Both pre- and post-MI treatments with AdTNFR1 were deleterious in a mouse MI model. Thus, TNF-α may play not only toxic but also protective roles in MI.
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