title: Cilostazol protects vessels against hyperglycemic injury and accelerates healing after implantation of drug-eluting stent in a type 1 diabetes mellitus rat aorta stent model.
abstract: OBJECTIVE
  Cilostazol, a selective phosphodiesterase-3 (PDE-3) inhibitor, can effectively suppress platelet activation and attenuate the increase in carotid intima-media thickness in diabetes mellitus (DM) patients. Therefore, we investigated whether cilostazol had effects on the healing process after implantation of a drug-eluting stent (DES) in a rat model of type 1 DM.
  
  
  RESULTS
  Streptozotocin-induced DM rats were divided into 2 groups in which cilostazol (30 mg/kg/day; DM-Cilostazol) or vehicle (DM-Vehicle) was orally administered. Age-matched rats treated with the vehicle were used as a control group (NDM-Vehicle). After 4 weeks, cilostazol changed the expression of vascular cell adhesion molecule and intercellular adhesion molecule and the apoptotic cell ratio of the media (DM-Vehicle: 53.5 ± 9.8%, DM-Cilostazol: 26.4 ± 8.3%, p < 0.05) in the aortic wall. Also, in a modified aortic ring test, cilostazol preserved the angiogenic potential of the aorta ([height of the sprouting tubes] DM-Vehicle: 0 ± 0 μm, DM-Cilostazol: 344.6 ± 236.8 μm, p < 0.05). After implantation of paclitaxel-eluting stents (PES) in rats treated with cilostazol or vehicle, thrombus formation, deposition of fibrin, and infiltration of inflammatory cells were attenuated by cilostazol. In particular, the re-endothelialization by von Willebrand factor expression in the DM-PES-Cilostazol group was enhanced compared with that in the DM-PES-Vehicle group.
  
  
  CONCLUSIONS
  Cilostazol has potential for protecting vessels against hyperglycemic injury and for accelerating the healing process after implantation of DES.
authors.affiliation: Heart Research Center, Chonnam National University Hospital, Gwangju, Republic of Korea.
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Kwon
authors.forename: Yong Sook
authors.initials: YS
authors.lastname: Kim
authors.forename: Hyang Hee
authors.initials: HH
authors.lastname: Cho
authors.forename: Hae Jin
authors.initials: HJ
authors.lastname: Kee
authors.forename: Moon Hwa
authors.initials: MH
authors.lastname: Hong
authors.forename: Wan Seok
authors.initials: WS
authors.lastname: Kang
authors.forename: Hye-Yun
authors.initials: HY
authors.lastname: Jeong
authors.forename: Myung Ho
authors.initials: MH
authors.lastname: Jeong
authors.forename: Youngkeun
authors.initials: Y
authors.lastname: Ahn
mesh_terms: D000284:Administration, Oral; D000800:Angioplasty, Balloon / Q000009:adverse effects / Q000295:instrumentation*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism*; D000077407:Cilostazol; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D054855:Drug-Eluting Stents; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D009389:Neovascularization, Pathologic; D017239:Paclitaxel / Q000008:administration & dosage; D058987:Phosphodiesterase 3 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011474:Prosthesis Design; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D058987:Phosphodiesterase 3 Inhibitors; D013777:Tetrazoles; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D000077407:Cilostazol; D017239:Paclitaxel