Soluble Tumor Necrosis Factor Receptor Abrogates Myocardial Inflammation but Not Hypertrophy in Cytokine-Induced Cardiomyopathy by Toru Kubota, George.

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Soluble Tumor Necrosis Factor Receptor Abrogates Myocardial Inflammation but Not Hypertrophy in Cytokine-Induced Cardiomyopathy by Toru Kubota, George S. Bounoutas, Masayuki Miyagishima, Toshiaki Kadokami, Virginia J. Sanders, Christina Bruton, Paul D. Robbins, Charles F. McTiernan, and Arthur M. Feldman Circulation Volume 101(21):2518-2525 May 30, 2000 Copyright © American Heart Association, Inc. All rights reserved.

Plasma levels of TNFRI after inoculation with AdTNFRI. Plasma levels of TNFRI after inoculation with AdTNFRI. Values are mean±SD (n=4 to 7). Toru Kubota et al. Circulation. 2000;101:2518-2525 Copyright © American Heart Association, Inc. All rights reserved.

Hematoxylin-eosin staining of myocardium: (A) wild-type mouse, (B) transgenic mouse, (C) transgenic mouse 2 weeks after inoculation with AdLacZ, and (D) transgenic mouse 2 weeks after inoculation with AdTNFRI. Hematoxylin-eosin staining of myocardium: (A) wild-type mouse, (B) transgenic mouse, (C) transgenic mouse 2 weeks after inoculation with AdLacZ, and (D) transgenic mouse 2 weeks after inoculation with AdTNFRI. Toru Kubota et al. Circulation. 2000;101:2518-2525 Copyright © American Heart Association, Inc. All rights reserved.

Nuclear density of myocardium: wild-type mice (WT), transgenic mice (TG), transgenic mice 2 weeks after inoculation with AdLacZ (TG+AdLacZ), and transgenic mice 2 weeks after inoculation with AdTNFRI (TG+AdTNFRI). Nuclear density of myocardium: wild-type mice (WT), transgenic mice (TG), transgenic mice 2 weeks after inoculation with AdLacZ (TG+AdLacZ), and transgenic mice 2 weeks after inoculation with AdTNFRI (TG+AdTNFRI). Values are mean±SD (n=5 to 6). *P<0.05 vs WT, †P<0.05 TG+AdTNFRI vs TG+AdLacZ. Toru Kubota et al. Circulation. 2000;101:2518-2525 Copyright © American Heart Association, Inc. All rights reserved.

RT-PCR assessment of ICAM-1 expression (top) in ventricular RNA isolated from wild-type (WT), TNF-α transgenic (TNF1.6), and TNF-α transgenic mice 2 weeks after inoculation with AdTNFRI (TNF1.6+AdTNFRI). RT-PCR assessment of ICAM-1 expression (top) in ventricular RNA isolated from wild-type (WT), TNF-α transgenic (TNF1.6), and TNF-α transgenic mice 2 weeks after inoculation with AdTNFRI (TNF1.6+AdTNFRI). RT-PCR assessment of total (endogenous and transgene-driven) TNF-α expression (bottom) in same animals. M indicates DNA marker; size is in base pairs. Toru Kubota et al. Circulation. 2000;101:2518-2525 Copyright © American Heart Association, Inc. All rights reserved.

Representative images of multiprobe RPA: (A) mCK-3b, (B) mCK-2b, (C) mCK-1b, and (D) mCK-5. Representative images of multiprobe RPA: (A) mCK-3b, (B) mCK-2b, (C) mCK-1b, and (D) mCK-5. Animal group abbreviations as in Figure 3. LT indicates lymphotoxin; IL, interleukin; IFN, interferon; TGF, transforming growth factor; MIF, macrophage inflammatory protein; IP, interferon-inducible protein; and TCA, T-cell activation gene. Toru Kubota et al. Circulation. 2000;101:2518-2525 Copyright © American Heart Association, Inc. All rights reserved.

Protein levels of cytokines in myocardium: (A) TNF-α, (B) IL-1β, and (C) MCP-1. Protein levels of cytokines in myocardium: (A) TNF-α, (B) IL-1β, and (C) MCP-1. Abbreviations as in Figure 3. Values are mean±SD (n=6). *P<0.05 vs WT, †P<0.05 TG+AdTNFRI vs TG+AdLacZ. Toru Kubota et al. Circulation. 2000;101:2518-2525 Copyright © American Heart Association, Inc. All rights reserved.

Immunohistochemical staining of myocardium of transgenic mice for (A) TNF-α, (B) IL-1β, and (C) MCP-1. Immunohistochemical staining of myocardium of transgenic mice for (A) TNF-α, (B) IL-1β, and (C) MCP-1. Arrows indicate positive-stained interstitial cells. Toru Kubota et al. Circulation. 2000;101:2518-2525 Copyright © American Heart Association, Inc. All rights reserved.

Transcript levels of cardiac-specific genes: (A) α-MHC, (B) β-MHC, (C) ANF, (D) SERCA, and (E) phospholamban. Transcript levels of cardiac-specific genes: (A) α-MHC, (B) β-MHC, (C) ANF, (D) SERCA, and (E) phospholamban. Values are mean±SD (n=6 to 12). *P<0.05 vs WT, †P<0.05 TG+AdTNFRI vs TG+AdLacZ. Toru Kubota et al. Circulation. 2000;101:2518-2525 Copyright © American Heart Association, Inc. All rights reserved.

M-mode echocardiography from (A) wild-type controls, (B) TNF-α transgenic mice, and (C) transgenic mice with TNFRI treatment. M-mode echocardiography from (A) wild-type controls, (B) TNF-α transgenic mice, and (C) transgenic mice with TNFRI treatment. In TNF-α transgenic mice, left ventricular enlargement but not left ventricular wall thickening was reversed by TNFRI treatment. Toru Kubota et al. Circulation. 2000;101:2518-2525 Copyright © American Heart Association, Inc. All rights reserved.