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Quantitation of Endothelial Cell Adhesiveness In Vitro
10:24

Quantitation of Endothelial Cell Adhesiveness In Vitro

Published on: June 18, 2015

Carvedilol inhibits tumor necrosis factor-alpha-induced endothelial transcription factor activation, adhesion

Jaw-Wen Chen1, Feng-Yen Lin, Yung-Hsiang Chen

  • 1National Yang-Ming University School of Medicine, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, 201, Sec 2, Shih-Pai Road, Taipei, Taiwan 112, Republic of China. jwchen@vghtpe.gov.tw

Arteriosclerosis, Thrombosis, and Vascular Biology
|September 18, 2004
PubMed

Insights

Carvedilol effectively reduces tumor necrosis factor-alpha (TNF-alpha)-induced endothelial cell adhesiveness by inhibiting reactive oxygen species (ROS) and key transcription factors, suggesting a role in preventing atherosclerosis.

Area of Science:

  • Cardiovascular Research
  • Molecular Biology
  • Pharmacology

Background:

  • Endothelial adhesiveness to mononuclear cells (MNCs) is an early indicator of atherosclerosis.
  • Tumor necrosis factor-alpha (TNF-alpha) significantly increases this endothelial adhesiveness.
  • Identifying agents that can inhibit this process is crucial for developing atherosclerosis treatments.

Purpose of the Study:

  • To investigate the potential of carvedilol, a known antioxidant and adrenoceptor antagonist, in inhibiting TNF-alpha-induced endothelial adhesiveness.
  • To compare carvedilol's effects with other agents like probucol, propanolol, and prazosin.
  • To elucidate the molecular mechanisms underlying carvedilol's action.

Main Methods:

  • Human mononuclear cells (MNCs) were isolated from healthy subjects.
  • Human aortic endothelial cells (HAECs) were pretreated with carvedilol, probucol, propanolol, or prazosin before TNF-alpha stimulation.
  • Expression of adhesion molecules (VCAM-1, E-selectin), intracellular reactive oxygen species (ROS) production, and transcription factor activation (NF-kappa B, AP-1) were measured.

Main Results:

  • Carvedilol and probucol significantly reduced TNF-alpha-stimulated endothelial adhesiveness to MNCs; propanolol and prazosin did not.
  • Carvedilol inhibited both VCAM-1 and E-selectin expression, while probucol only inhibited VCAM-1.
  • Carvedilol significantly decreased TNF-alpha-induced intracellular ROS production and the activation of NF-kappa B and AP-1 pathways.

Conclusions:

  • Carvedilol effectively reduces TNF-alpha-induced endothelial adhesiveness by inhibiting ROS production and transcription factor activation.
  • The inhibition of VCAM-1 and E-selectin expression by carvedilol contributes to its anti-atherogenic potential.
  • These findings suggest carvedilol may play a significant role in the clinical management of atherosclerosis.
Abstract

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