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

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