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Herbal Munziq Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting Inflammation
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Role of TNF-alpha-induced reactive oxygen species in endothelial dysfunction during reperfusion injury

Xue Gao1, Hanrui Zhang, Souad Belmadani

  • 1Department of Internal Medicine, Dalton Cardiovascular Research Center, University of Missouri-Columbia, Columbia, MO 65211, USA.

American Journal of Physiology. Heart and Circulatory Physiology
|October 14, 2008
PubMed

Insights

Neutralizing tumor necrosis factor-alpha (TNF-alpha) during reperfusion protects endothelial function and reduces oxidative stress after myocardial ischemia. This effect is independent of neutrophil activation, highlighting a novel therapeutic target.

Area of Science:

  • Cardiovascular Research
  • Immunology
  • Oxidative Stress

Background:

  • Myocardial ischemia-reperfusion (I/R) injury leads to endothelial dysfunction and oxidative stress.
  • Tumor necrosis factor-alpha (TNF-alpha) is implicated in inflammatory responses following I/R.
  • The specific role of TNF-alpha in I/R-induced endothelial dysfunction requires further elucidation.

Purpose of the Study:

  • To investigate the role of TNF-alpha neutralization in mitigating endothelial dysfunction and oxidative stress during myocardial I/R.
  • To determine the cellular sources of TNF-alpha expression post-I/R.
  • To explore the mechanisms by which TNF-alpha contributes to I/R-induced vascular injury.

Main Methods:

  • A mouse model of myocardial ischemia-reperfusion (30 min ischemia/90 min reperfusion).
  • Administration of TNF-alpha neutralizing antibodies at the time of reperfusion.
  • Assessment of TNF-alpha expression, endothelial function (nitric oxide-mediated dilation), superoxide production, and enzyme activities (NAD(P)H oxidase, xanthine oxidase).

Main Results:

  • I/R increased TNF-alpha expression in vascular smooth muscle cells, mast cells, and macrophages, but not endothelial cells.
  • Anti-TNF-alpha treatment attenuated TNF-alpha expression, improved endothelial function, and reduced superoxide production.
  • I/R elevated NAD(P)H oxidase and xanthine oxidase activity; anti-TNF-alpha administration blocked this increase.

Conclusions:

  • Myocardial ischemia induces TNF-alpha expression, contributing to vascular oxidative stress and coronary endothelial dysfunction.
  • Neutralizing TNF-alpha at reperfusion offers a protective effect on endothelial function, independent of neutrophil activation.
  • Targeting TNF-alpha presents a potential therapeutic strategy for managing ischemia-reperfusion injury.

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