A disintegrin and metalloprotease 17 mediates neointimal hyperplasia in vasculature

Hypertension. 2011 Apr;57(4):841-5. doi: 10.1161/HYPERTENSIONAHA.110.166892. Epub 2011 Feb 28.

Abstract

The requirement of a metalloprotease, a disintegrin and metalloprotease 17 (ADAM17) for the growth of cultured vascular smooth muscle cells has been demonstrated in vitro. However, whether this metalloprotease is responsible for vascular remodeling in vivo remains unanswered. Rat carotid arteries were analyzed 2 weeks after a balloon angioplasty. The neointimal cells were strongly positive for ADAM17 immunostaining. Marked inhibition of intimal hyperplasia was observed in a dominant-negative ADAM17 adenovirus-treated carotid artery. Proliferating cell nuclear antigen-positive cells and phospho-epidermal growth factor receptor-positive cells in the neointima were reduced by dominant-negative ADAM17 as well. In contrast, the neointima formation, proliferating cell nuclear antigen-positive cells, and phospho-epidermal growth factor receptor-positive cells were markedly enhanced by wild-type ADAM17 adenovirus. In conclusion, ADAM17 activation is involved in epidermal growth factor receptor activation and subsequent neointimal hyperplasia after vascular injury. ADAM17 could be a novel therapeutic target for pathophysiological vascular remodeling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / metabolism*
  • ADAM17 Protein
  • Angioplasty, Balloon
  • Animals
  • Carotid Arteries / metabolism
  • Carotid Arteries / pathology*
  • Carotid Artery Injuries / metabolism*
  • Carotid Artery Injuries / pathology
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • ErbB Receptors / metabolism
  • Hyperplasia / metabolism
  • Immunohistochemistry
  • Male
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / pathology
  • Neointima / metabolism
  • Neointima / pathology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • ErbB Receptors
  • ADAM Proteins
  • ADAM17 Protein
  • Adam17 protein, rat