Inhibition of experimental intimal thickening in mice lacking a novel G-protein-coupled receptor.
BACKGROUND
Vascular restenosis attributable to intimal thickening remains a major problem after percutaneous transluminal coronary angioplasty (PTCA).


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.
Tsukada
Shuichi
S
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Japan.
Iwai
Masaru
M
Nishiu
Jun
J
Itoh
Makoto
M
Tomoike
Hitonobu
H
Horiuchi
Masatsugu
M
Nakamura
Yusuke
Y
Tanaka
Toshihiro
T
D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D019556:COS Cells; D002460:Cell Line; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D003251:Constriction, Pathologic / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000378:metabolism* / Q000473:pathology; D019204:GTP-Binding Proteins / Q000378:metabolism; D018390:Gene Targeting; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D017539:Tunica Intima / Q000378:metabolism* / Q000473:pathology; D017540:Tunica Media / Q000378:metabolism / Q000473:pathology
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins