title: Local insulin application on the carotid artery inhibits neointima formation.
abstract: Anti-mitogenic agents currently used to prevent restenosis in drug-eluting stents delay re-endothelialization. Delayed re-endothelialization is now considered as the main cause of late stent thrombosis with drug-eluting stents, which emphasizes the need for new treatments. We have shown that systemic insulin treatment decreases neointimal growth and accelerates re-endothelialization after arterial injury in a rat model of restenosis. However, systemic insulin treatment cannot be given to non-diabetic individuals because of the risk of hypoglycemia. Thus, we investigated whether local insulin treatment is also effective in reducing neointimal growth after arterial injury. Rats were given local vehicle or local insulin delivered via Pluronic gel applied around the carotid artery immediately following balloon injury. Plasma glucose and systemic insulin levels were not affected by local insulin treatment. Insulin decreased intimal area at 28 days (P < 0.05) and also inhibited vascular smooth muscle cell migration by 60% at 4 days (P < 0.05). NPH (a longer-lasting insulin) also decreased neointimal area. These results indicate that local insulin treatment can lead to decreased restenosis, suggesting a protective vascular effect of insulin in vivo and that local insulin treatment, possibly via insulin-eluting stents, may be clinically relevant.
authors.affiliation: a Department of Physiology, Medical Science Building, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Chiang
authors.forename: Danna M
authors.initials: DM
authors.lastname: Breen
authors.forename: June
authors.initials: J
authors.lastname: Guo
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Mori
authors.forename: Adria
authors.initials: A
authors.lastname: Giacca
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D054855:Drug-Eluting Stents; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D006083:Graft Occlusion, Vascular / Q000188:drug therapy / Q000473:pathology; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology; D058426:Neointima / Q000188:drug therapy* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D007328:Insulin