Effects of balloon injury on neointimal hyperplasia in streptozotocin-induced diabetes and in hyperinsulinemic nondiabetic pancreatic islet-transplanted rats

Citation
C. Indolfi et al., Effects of balloon injury on neointimal hyperplasia in streptozotocin-induced diabetes and in hyperinsulinemic nondiabetic pancreatic islet-transplanted rats, CIRCULATION, 103(24), 2001, pp. 2980-2986
Citations number
35
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
CIRCULATION
ISSN journal
00097322 → ACNP
Volume
103
Issue
24
Year of publication
2001
Pages
2980 - 2986
Database
ISI
SICI code
0009-7322(20010619)103:24<2980:EOBION>2.0.ZU;2-2
Abstract
Background-The mechanisms of increased neointimal hyperplasia after coronar y interventions in diabetic patients are still unknown. Methods and Results-Glucose and insulin effects on in vitro vascular smooth muscle cell (VSMC) proliferation and migration were assessed. The effect o f balloon injury on neointimal hyperplasia was studied in streptozotocin-in duced diabetic rats with or without adjunct insulin therapy. To study the e ffect of balloon injury in nondiabetic rats with hyperinsulinemia, pancreat ic islets were transplanted under the kidney capsule in normal rats. Glucos e did not increase VSMC proliferation and migration in vitro. In contrast, insulin induced a significant increase in VSMC proliferation and migration in cell cultures. Furthermore, in VSMC culture, insulin increased MAPK acti vation. A reduction in neointimal hyperplasia was consistently documented a fter vascular injury in hyperglycemic streptozotocin-induced diabetic rats. Insulin therapy significantly increased neointimal hyperplasia in these ra ts. This effect of hyperinsulinemia was totally abolished by transfection o n the arterial wall of the N17H-ras-negative mutant gene. Finally, after ex perimental balloon angioplasty in hyperinsulinemic nondiabetic islet-transp lanted rats, a significant increase in neointimal hyperplasia was observed. Conclusions-In rats with streptozotocin-induced diabetes, balloon injury wa s not associated with an increase in neointimal formation. Exogenous insuli n administration in diabetic rats and islet transplantation in nondiabetic rats increased both blood insulin levels and neointimal hyperplasia after b alloon injury. Hyperinsulinemia through activation of the ras/MAPK pathway, rather than hyperglycemia per se, seems to be of crucial importance in det ermining the exaggerated neointimal hyperplasia after balloon angioplasty i n diabetic animals.