Dominant negative insulin-like growth factor-1 receptor inhibits neointimal formation through suppression of vascular smooth muscle cell migration and proliferation, and induction of apoptosis.
Blocking of the IGF-1 signaling pathway targeting the IGF-1 receptor (IGF-1R) provides a potential treatment strategy for restenosis. In this study, we have examined the effects of a dominant negative IGF-1R (IGF-1Rt) on primary rat VSMCs in vitro and on injured rat carotid artery in vivo. Ad/IGF-1Rt infection inhibited VSMC migration and proliferation, and it also induced apoptosis by inhibiting phosphorylation of Akt and phosphorylation of ERK1/2. Consistent with the anti-proliferative and apoptotic effects in vitro, the Ad/IGF-1Rt infection markedly reduced neointimal formation in carotid injury model. Ad/IGF-1Rt treated carotid arteries exhibited a suppressed proliferation index, PCNA expression, and also were stained positive for TUNEL assay. These results indicate that a dominant negative IGF-1R has the potential to reduce neointimal formation of injured rats' carotid arteries. The delivery of dominant negative IGF-1R by adenoviral or other vectors may provide a useful strategy for inhibiting restenosis after angioplasty.
Lim
Hyun-Joung
HJ
BK21 project of Medical Science, Republic of Korea.
Park
Hyun-Young
HY
Ko
Young-Guk
YG
Lee
Sea-Hyoung
SH
Cho
Seung-Yeon
SY
Lee
Eun Jig
EJ
Jameson
J Larry
JL
Jang
Yangsoo
Y
D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D023903:Coronary Restenosis / Q000209:etiology / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control*; D018014:Gene Transfer Techniques; D005799:Genes, Dominant / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000819:agonists* / Q000235:genetics*; D016896:Treatment Outcome; D017539:Tunica Intima / Q000187:drug effects / Q000254:growth & development / Q000473:pathology
D017526:Receptor, IGF Type 1