Resveratrol attenuates oxidative stress induced by balloon injury in the rat carotid artery through actions on the ERK1/2 and NF-kappa B pathway

Cell Physiol Biochem. 2013;31(2-3):230-41. doi: 10.1159/000343364. Epub 2013 Feb 14.

Abstract

Background/aim: Oxidative stress plays a critical role in pathogenesis of the neointimal arterial hyperplasia. The aim of the study was to evaluate effects of resveratrol (RSV) on the vascular hyperplasia stimulated by oxidative damage.

Methods: Balloon vascular injury was induced in rats that were intraperitonealy exposed to resveratrol (1 mg/kg) on 7 or 14 days after surgical procedure. Animals were euthanized on 7 or 14 days after operation. The blood level of 8-iso-prostaglandin F2α, arterial morphology as well as expression of monocyte chemotactic protein-1 and interleukin-6 in carotid wall were measured. Vascular smooth muscle cells (VSMCs) were isolated from the thoracic aorta. Cellular proliferation and migration assays, reactive oxygen species (ROS), superoxide dismutase (SOD) and NADPH oxidative activity, protein level of β-actin, histone H3, NF-ĸB p65, IĸB, ERK1/2, phospho-ERK1/2, phospho-p38 as well as NF-ĸB transcription activity were evaluated in-vitro after angiotensin II stimulation and resveratrol (50-200 µmol/L) treatment.

Results: Significant decreases in neointimal/medial area, serum prostaglandin level and genes expression were found in rats treated with resveratrol, when compared to the control group. Significant changes were also revealed for proliferation and migration rates, ROS level, as well as SOD, NADPH oxidase, ERK1/2 phosphorylation and NF-ĸB transcriptional activity in cell cultures exposed to highest dose of resveratrol. Insignificant changes were observed for NF-kappaB p65 translocation and IĸB degradation, p38 phosphorylation in MAPK pathway.

Conclusion: Resveratrol significantly suppressed the neointimal hyperplasia after balloon injury through inhibition of oxidative stress and inflammation by blocking the ERK1/2/NF-kappa B pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Aorta, Thoracic / cytology
  • Carotid Arteries / drug effects
  • Carotid Arteries / metabolism
  • Carotid Arteries / pathology
  • Carotid Artery Injuries / metabolism
  • Carotid Artery Injuries / pathology
  • Cell Movement / drug effects
  • Cells, Cultured
  • Chemokine CCL2 / metabolism
  • Dinoprost / analogs & derivatives
  • Dinoprost / blood
  • Disease Models, Animal
  • Interleukin-6 / metabolism
  • Male
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / metabolism
  • NADPH Oxidases / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Oxidative Stress / drug effects*
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Resveratrol
  • Signal Transduction / drug effects
  • Stilbenes / pharmacology*
  • Transcription Factor RelA / metabolism
  • Transcription, Genetic
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antioxidants
  • Ccl2 protein, rat
  • Chemokine CCL2
  • Interleukin-6
  • NF-kappa B
  • Reactive Oxygen Species
  • Stilbenes
  • Transcription Factor RelA
  • 8-epi-prostaglandin F2alpha
  • Dinoprost
  • NADPH Oxidases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • Resveratrol