Related Experiment Video
Updated: Apr 12, 2026
Vascular Balloon Injury and Intraluminal Administration in Rat Carotid Artery
Published on: December 23, 2014
The effect of insulin to decrease neointimal growth after arterial injury is endothelial nitric oxide
June Guo1, Danna M Breen1, Troy J Pereira2
1Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Abstract:
In vitro, insulin has mitogenic effects on vascular smooth muscle cells (VSMC) but also has protective effects on endothelial cells by stimulating nitric oxide (NO) production and endothelial nitric oxide synthase (eNOS) expression. Furthermore, NOS inhibition attenuates the effect of insulin to inhibit VSMC migration in vitro. Using an in vivo model, we have previously shown that insulin decreases neointimal growth and cell migration and increases re-endothelialization after arterial injury in normal rats. Since insulin can stimulate NOS, and NO can decrease neointimal growth, we hypothesized that NOS, and more specifically eNOS was required for the effects of insulin in vivo. Rats were given subcutaneous insulin implants (3 U/day) alone or with the NOS inhibitor l-NAME (2 mg kg(-1) day(-1)) 3 days before arterial (carotid or aortic) balloon catheter injury. Insulin decreased both neointimal area (P < 0.01) and cell migration (P < 0.01), and increased re-endothelialization (P < 0.05). All of these effects were prevented by the co-administration of l-NAME. Insulin was found to decrease inducible NOS expression (P < 0.05) but increase eNOS phosphorylation (P < 0.05). These changes were also translated at the functional level where insulin improved endothelial-dependent vasorelaxation. To further study the NOS isoform involved in insulin action, s.c. insulin (0.1 U/day) was given to wild-type and eNOS knockout mice. We found that insulin was effective at decreasing neointimal formation in wild-type mice after wire injury of the femoral artery, whereas this effect of insulin was absent in eNOS knockout mice. These results show that the vasculoprotective effect of insulin after arterial injury is mediated by an eNOS-dependent mechanism.
Insights
Insulin
Area of Science:
- Vascular biology
- Endocrinology
- Cardiovascular research
Background:
- Insulin exhibits dual effects on vascular cells in vitro: mitogenic on smooth muscle cells and protective on endothelial cells.
- Insulin stimulates nitric oxide (NO) production and endothelial nitric oxide synthase (eNOS) expression, crucial for vascular health.
- Previous in vivo studies demonstrated insulin's ability to reduce neointimal growth and enhance re-endothelialization after arterial injury.
Purpose of the Study:
- To investigate the role of nitric oxide synthase (NOS), specifically eNOS, in mediating insulin's vasculoprotective effects in vivo.
- To determine if the beneficial effects of insulin on neointimal formation and re-endothelialization are dependent on NOS activity.
Main Methods:
- Rats received insulin implants with or without the NOS inhibitor l-NAME before arterial balloon injury.
- Insulin's effects on neointimal area, cell migration, and re-endothelialization were assessed.
- Wild-type and eNOS knockout mice were treated with insulin to evaluate neointimal formation after femoral artery injury.
Main Results:
- Insulin significantly reduced neointimal area and cell migration while increasing re-endothelialization in rats.
- Co-administration of l-NAME abolished all beneficial effects of insulin, indicating a critical role for NOS.
- Insulin increased eNOS phosphorylation and improved endothelial-dependent vasorelaxation.
- Insulin's protective effect against neointimal formation was observed in wild-type mice but absent in eNOS knockout mice.
Conclusions:
- The vasculoprotective effects of insulin following arterial injury are critically dependent on the endothelial nitric oxide synthase (eNOS) pathway.
- Insulin promotes vascular healing through an eNOS-dependent mechanism, highlighting its therapeutic potential in cardiovascular diseases.
