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