کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5944460 1172344 2015 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The effect of insulin to decrease neointimal growth after arterial injury is endothelial nitric oxide synthase-dependent
ترجمه فارسی عنوان
اثر انسولین برای کاهش رشد نوینتیمال پس از آسیب شریان، وابسته به سنتاز وابسته به نیتریک اتیل آندوتلیال است
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
چکیده انگلیسی


- Insulin decreased neointimal area after arterial injury in both rats and mice.
- This effect of insulin was inhibited by a nitric oxide synthase (NOS) inhibitor.
- This effect of insulin was absent in endothelial NOS-knockout mice.

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Atherosclerosis - Volume 241, Issue 1, July 2015, Pages 111-120
نویسندگان
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