Soluble TNF receptors prevent apoptosis in infiltrating cells and promote ventricular rupture and remodeling after myocardial infarction

Yoshiya Monden, Toru Kubota, Takaki Tsutsumi, Takahiro Inoue, Shunichi Kawano, Natsumi Kawamura, Tomomi Ide, Kensuke Egashira, Hiroyuki Tsutsui, Kenji Sunagawa

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)794-805
Number of pages12
JournalCardiovascular research
Volume73
Issue number4
DOIs
Publication statusPublished - Mar 1 2007

Fingerprint

Ventricular Remodeling
Tumor Necrosis Factor Receptors
Rupture
Myocardial Infarction
Apoptosis
Adenoviridae
Tumor Necrosis Factor-alpha
Myocardium
Clinical Protocols
Ligation
Fibrosis
Ventricular Dysfunction
Therapeutics
Poisons
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Intravenous Injections
Coronary Vessels
Cardiovascular Diseases
Immunoglobulin G

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Soluble TNF receptors prevent apoptosis in infiltrating cells and promote ventricular rupture and remodeling after myocardial infarction. / Monden, Yoshiya; Kubota, Toru; Tsutsumi, Takaki; Inoue, Takahiro; Kawano, Shunichi; Kawamura, Natsumi; Ide, Tomomi; Egashira, Kensuke; Tsutsui, Hiroyuki; Sunagawa, Kenji.

In: Cardiovascular research, Vol. 73, No. 4, 01.03.2007, p. 794-805.

Research output: Contribution to journalArticle

Monden, Yoshiya ; Kubota, Toru ; Tsutsumi, Takaki ; Inoue, Takahiro ; Kawano, Shunichi ; Kawamura, Natsumi ; Ide, Tomomi ; Egashira, Kensuke ; Tsutsui, Hiroyuki ; Sunagawa, Kenji. / Soluble TNF receptors prevent apoptosis in infiltrating cells and promote ventricular rupture and remodeling after myocardial infarction. In: Cardiovascular research. 2007 ; Vol. 73, No. 4. pp. 794-805.
@article{31746aab112e40ddb82d88e33952ad85,
title = "Soluble TNF receptors prevent apoptosis in infiltrating cells and promote ventricular rupture and remodeling after myocardial infarction",
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.",
author = "Yoshiya Monden and Toru Kubota and Takaki Tsutsumi and Takahiro Inoue and Shunichi Kawano and Natsumi Kawamura and Tomomi Ide and Kensuke Egashira and Hiroyuki Tsutsui and Kenji Sunagawa",
year = "2007",
month = "3",
day = "1",
doi = "10.1016/j.cardiores.2006.12.016",
language = "English",
volume = "73",
pages = "794--805",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - Soluble TNF receptors prevent apoptosis in infiltrating cells and promote ventricular rupture and remodeling after myocardial infarction

AU - Monden, Yoshiya

AU - Kubota, Toru

AU - Tsutsumi, Takaki

AU - Inoue, Takahiro

AU - Kawano, Shunichi

AU - Kawamura, Natsumi

AU - Ide, Tomomi

AU - Egashira, Kensuke

AU - Tsutsui, Hiroyuki

AU - Sunagawa, Kenji

PY - 2007/3/1

Y1 - 2007/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33846889552&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846889552&partnerID=8YFLogxK

U2 - 10.1016/j.cardiores.2006.12.016

DO - 10.1016/j.cardiores.2006.12.016

M3 - Article

C2 - 17266945

AN - SCOPUS:33846889552

VL - 73

SP - 794

EP - 805

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 4

ER -