Improved myocardial ischemia/reperfusion injury in mice lacking tumor necrosis factor-α

Maekawa, Naoya; Wada, Hisayasu; Kanda, Tsugiyasu; Niwa, Toshifumi; Yamada, Yasuhiro; Saito, Kuniaki; Fujiwara, Hisayoshi; Sekikawa, Kenji; Seishima, Mitsuru

doi:10.1016/s0735-1097(02)01738-2

Cited by 184 publications

(116 citation statements)

References 21 publications

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“…Sun and coworkers demonstrated that TNF-α null mice were protected from cardiac rupture and chronic dysfunction following infarction, and exhibited suppressed inflammation and attenuated MMP activity in comparison with wildtype animals [151]. Several other investigations have suggested an essential role for TNF-α in mediating inflammatory injury following infarction [152], [145]. Inhibition studies have produced contradictory findings regarding the effects of TNF-α neutralization on the infarcted heart.…”

Section: Tnf-αmentioning

confidence: 99%

The immune system and cardiac repair

Frangogiannis

2008

Pharmacological Research

572

499

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Myocardial infarction is the most common cause of cardiac injury and results in acute loss of a large number of myocardial cells. Because the heart has negligible regenerative capacity, cardiomyocyte death triggers a reparative response that ultimately results in formation of a scar and is associated with dilative remodeling of the ventricle. Cardiac injury activates innate immune mechanisms initiating an inflammatory reaction. Toll Like Receptor-mediated pathways, the complement cascade and reactive oxygen generation induce Nuclear Factor (NF)-κB activation and upregulate chemokine and cytokine synthesis in the infarcted heart. Chemokines stimulate the chemotactic recruitment of inflammatory leukocytes into the infarct, while cytokines promote adhesive interactions between leukocytes and endothelial cells, resulting in transmigration of inflammatory cells into the site of injury. Monocyte subsets play distinct roles in phagocytosis of dead cardiomyocytes and in granulation tissue formation through the release of growth factors. Clearance of dead cells and matrix debris may be essential for resolution of inflammation and transition into the reparative phase. Transforming Growth Factor (TGF)-β plays a crucial role in cardiac repair by suppressing inflammation while promoting myofibroblast phenotypic modulation and extracellular matrix deposition. Myofibroblast proliferation and angiogenesis result in formation of highly vascularized granulation tissue. As the healing infarct matures, fibroblasts become apoptotic and a collagen-based matrix is formed, while many infarct neovessels acquire a muscular coat and uncoated vessels regress. Timely resolution of the inflammatory infiltrate and spatial containment of the inflammatory and reparative response into the infarcted area are essential for optimal infarct healing. Targeting inflammatory pathways following infarction may reduce cardiomyocyte injury and attenuate adverse remodeling. In addition, understanding the role of the immune system in cardiac repair is necessary in order to design optimal strategies for cardiac regeneration.

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Section: Tnf-αmentioning

confidence: 99%

The immune system and cardiac repair

Frangogiannis

2008

Pharmacological Research

572

499

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“…1). Because IL-1␤ and TNF-␣ are B-responsive proinflammatory cytokines and play an important role in myocardial inflammation and injury (34,35), we then explored the effects of IL-18 on IL-1␤ and TNF-␣ expression and determined whether IL-18 induces cytokine expression via NF-B activation. Fig.…”

Section: Il-18 Increases Nf-b Dna Binding Activity and Induces B-drivmentioning

confidence: 99%

Activation of Intrinsic and Extrinsic Proapoptotic Signaling Pathways in Interleukin-18-mediated Human Cardiac Endothelial Cell Death

Chandrasekar

Vemula

Surabhi

et al. 2004

Journal of Biological Chemistry

115

119

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“…23 On the basis of those results, we presumed that the TNF--induced upregulation of ICAM-1 plays an important role as an initial process of TNF--related cardiac injury. In a TNF-KO mouse model of ischemia -reperfusion reduction of nuclear-factor-kappa activation and ICAM-1 mRNA expression has been shown, 15 but in a permanent occlusion model of MI, no studies have elucidated the involvement of ICAM-1 and cellular infiltration in the inhibition of TNF-.…”

mentioning

confidence: 99%

Tumor-Necrosis-Factor-.ALPHA.-Gene-Deficient Mice Have Improved Cardiac Function Through Reduction of Intercellular Adhesion Molecule-1 in Myocardial Infarction

Sato

Suzuki

Shibata

et al. 2006

Circ J

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Improved myocardial ischemia/reperfusion injury in mice lacking tumor necrosis factor-α

Abstract: Tumor necrosis factor-alpha exacerbates myocardial I/R injury at an early stage of reperfusion by activating NF-kappaB, thereby inducing chemokines and adhesion molecules and facilitating leukocyte infiltration.

Cited by 184 publications

References 21 publications

The immune system and cardiac repair

The immune system and cardiac repair

Activation of Intrinsic and Extrinsic Proapoptotic Signaling Pathways in Interleukin-18-mediated Human Cardiac Endothelial Cell Death

Tumor-Necrosis-Factor-.ALPHA.-Gene-Deficient Mice Have Improved Cardiac Function Through Reduction of Intercellular Adhesion Molecule-1 in Myocardial Infarction

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