title: Effect of a dipeptidyl peptidase-IV inhibitor, des-fluoro-sitagliptin, on neointimal formation after balloon injury in rats.
abstract: 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.
  
  
  RESULTS
  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 dose-dependent 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-α 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 NFκB activation in VSMCs.
  
  
  CONCLUSIONS
  Sitagliptin has protective properties against restenosis after carotid injury and therapeutic implications for treating macrovascular complications of diabetes.
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Soo
authors.initials: S
authors.lastname: Lim
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Choi
authors.forename: Hayley
authors.initials: H
authors.lastname: Shin
authors.forename: Bong Jun
authors.initials: BJ
authors.lastname: Cho
authors.forename: Ho Seon
authors.initials: HS
authors.lastname: Park
authors.forename: Byung Yong
authors.initials: BY
authors.lastname: Ahn
authors.forename: Seon Mee
authors.initials: SM
authors.lastname: Kang
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Yoon
authors.forename: Hak Chul
authors.initials: HC
authors.lastname: Jang
authors.forename: Young-Bum
authors.initials: YB
authors.lastname: Kim
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
mesh_terms: D052242:Adiponectin / Q000097:blood; D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D002339:Carotid Arteries / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000201:enzymology; D018932:Chemokine CCL2 / Q000097:blood; D023903:Coronary Restenosis / Q000517:prevention & control*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011719:Pyrazines / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D020334:Rats, Inbred OLETF; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D017539:Tunica Intima / Q000187:drug effects* / Q000293:injuries
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D054873:Dipeptidyl-Peptidase IV Inhibitors; D017395:Plasminogen Activator Inhibitor 1; D011719:Pyrazines; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000068900:Sitagliptin Phosphate