Correction: Effect of a Dipeptidyl Peptidase-IV Inhibitor, Des-Fluoro-Sitagliptin, on Neointimal Formation after Balloon Injury in Rats

Background: Recently, it has been suggested that enhancement of incretin effect improves cardiac function.We investigated the effect of a DPP-IV inhibitor, des-fluoro-sitagliptin, in reducing occurrence of restenosis in carotid artery in response to balloon injury and the related mechanisms.Methods and Findings: Otsuka Long-Evans Tokushima Fatty rats were grouped into four: control (normal saline) and sitagliptin 100, 250 and 500 mg/kg per day (n = 10 per group).Sitagliptin or normal saline were given orally from 1 week before to 2 weeks after carotid injury.After 3 weeks of treatment, sitagliptin treatment caused a significant and dosedependent reduction in intima-media ratio (IMR) in obese diabetic rats.This effect was accompanied by improved glucose homeostasis, decreased circulating levels of high-sensitivity C-reactive protein (hsCRP) and increased adiponectin level.Moreover, decreased IMR was correlated significantly with reduced hsCRP, tumor necrosis factor-a and monocyte chemoattractant protein-1 levels and plasminogen activator inhibitor-1 activity.In vitro evidence with vascular smooth muscle cells (VSMCs) demonstrated that proliferation and migration were decreased significantly after sitagliptin treatment.In addition, sitagliptin increased caspase-3 activity and decreased monocyte adhesion and NFkB activation in VSMCs.Conclusions: Sitagliptin has protective properties against restenosis after carotid injury and therapeutic implications for treating macrovascular complications of diabetes.