Anti-proliferative and anti-inflammatory effects of topical MAPK inhibition in arterialized vein grafts. Academic Article uri icon

Overview

abstract

  • Vein graft failure following bypass surgery is a frequent and important clinical problem. The vascular injury caused by arterialization is responsible for vein graft intimal hyperplasia, a lesion generated by medial smooth muscle cell proliferation and migration into the intima, increased extracellular matrix deposition, and formation of a thick neointima. Development of the neointima into a typical atherosclerotic lesion and consequent stenosis ultimately result in vein graft failure. Endothelial damage, inflammation, and intracellular signaling through mitogen-activated protein kinases (MAPKs) have been implicated in the early stages of this process. We therefore investigated the effects of topical inhibition of ERK-1/2 MAPK activation on vascular cell proliferation and apoptosis, and on the inflammatory response in a canine model of vein graft arterialization. For this purpose, vein grafts were incubated with the MEK-1/2 inhibitor, UO126, ex vivo for 30 min before grafting. This treatment effectively abolished arterialization-induced ERK-1/2 activation, decreased medial cell proliferation, and increased apoptosis. UO126 treatment also inhibited the vein graft infiltration by myeloperoxidase-positive inflammatory cells that follows vein graft arterialization. Thus, topical ex vivo administration of MAPK inhibitors can provide a pharmacological tool to prevent or reduce the vascular cell responses that lead to vein graft intimal hyperplasia and graft failure.

publication date

  • November 22, 2005

Research

keywords

  • Anti-Inflammatory Agents
  • Apoptosis
  • Butadienes
  • Carotid Arteries
  • Inflammation
  • Jugular Veins
  • Mitogen-Activated Protein Kinases
  • Nitriles

Identity

Scopus Document Identifier

  • 33644925280

Digital Object Identifier (DOI)

  • 10.1096/fj.05-4114fje

PubMed ID

  • 16303874

Additional Document Info

volume

  • 20

issue

  • 2