Inhibition of experimental intimal thickening in mice lacking a novel G-protein-coupled receptor

Circulation. 2003 Jan 21;107(2):313-9. doi: 10.1161/01.cir.0000043804.29963.b4.

Abstract

Background: Vascular restenosis attributable to intimal thickening remains a major problem after percutaneous transluminal coronary angioplasty (PTCA).

Methods and results: Through differential-display analysis, we have identified a novel gene whose expression was increased after catheter injury of rabbit aorta. The gene that is expressed predominantly in vascular smooth muscle cells encodes a novel protein with 7 transmembrane domains, and we termed it ITR (intimal thickness-related receptor). The ITR sequence contains a motif common to the Rhodopsin-like GPCR (G-protein-coupled receptor) superfamily. In vivo analyses of this gene revealed that expression of ITR protein increased with intimal thickening induced by cuff placement around murine femoral artery. Furthermore, ITR-knockout mice were found to be resistant to this experimental intimal thickening.

Conclusions: ITR thus seems to be a novel receptor that may play a role in vascular remodeling and that may represent a good target for development of drugs in the prevention of vascular restenosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aorta / metabolism
  • Aorta / pathology
  • Base Sequence
  • COS Cells
  • Cell Line
  • Chromosomes, Human, Pair 13 / genetics
  • Constriction, Pathologic / genetics
  • Constriction, Pathologic / pathology
  • Constriction, Pathologic / prevention & control*
  • Disease Models, Animal
  • Femoral Artery / metabolism*
  • Femoral Artery / pathology
  • GTP-Binding Proteins / metabolism
  • Gene Targeting
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / pathology
  • Organ Specificity
  • RNA, Messenger / metabolism
  • Rabbits
  • Rats
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / deficiency
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism
  • Tunica Intima / metabolism*
  • Tunica Intima / pathology
  • Tunica Media / metabolism
  • Tunica Media / pathology

Substances

  • RNA, Messenger
  • Receptors, Cell Surface
  • GTP-Binding Proteins