title: Anti-inflammatory and anti-proliferative effects of CBS3830 in arterialized vein grafts in rats.
abstract: OBJECTIVE
  To investigated whether CBS3830, a highly selectively inhibitor of p38MAPK, could ameliorate inflammation and intimal hyperplasia in arterialized vein grafts (AVGs).
  
  
  METHODS
  Sixty male Sprague-Dawley rats underwent a reversed right jugular vein to common carotid artery interposition graft and were randomly treatment with vehicle (control) or single-dose (3 mg/kg, preoperative) or double-dose (3 mg/kg, preoperative and 4 d postoperative) CBS3830. Twenty rats underwent sham operation. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were determined by ELISA. Vein grafts were analyzed by intimal/medial morphometry, proliferating cell nuclear antigen (PCNA) expression, and p38MAPK phosphorylation.
  
  
  RESULTS
  TNF-α, IL-1β, and IL-6 gradually increased then slowly decreased in AVG rats. However, at 4 d and 7 d, TNF-α levels decreased by 37.5% and 29.5% (p = 0.003, 0.05, respectively) in the single-dose CBS3830 group, and by 37.6% and 32.5%, respectively (both p = 0.003) in the double-dose group compared with those of control. IL-1β levels significantly reduced at 4 d and 14 d in both dosage groups. IL-6 levels significantly reduced at 7 d in both groups. Intima and medial thickening were significantly reduced in both dosage treated groups at 7, 14, and 28 d (all p = 0.000) compared to the controls. Further study showed CBS3830 inhibited p38MAPK phosphorylation and decreased PCNA expression.
  
  
  CONCLUSIONS
  CBS3830 significantly decreases inflammation and intimal hyperplasia in AVGs.
authors.affiliation: The Cardiovascular Research Institute Laboratory, Department of Cardiovascular Surgery, 1st Hospital of Anhui Medical University , Hefei, Anhui , China .
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Zhao
authors.forename: Dietmar-Karl
authors.initials: DK
authors.lastname: Abendroth
authors.forename: Zheng-Chun
authors.initials: ZC
authors.lastname: Zhou
authors.forename: Yong-Zhi
authors.initials: YZ
authors.lastname: Liu
authors.forename: Fa-Ming
authors.initials: FM
authors.lastname: Pan
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Ge
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006083:Graft Occlusion, Vascular / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D006965:Hyperplasia; D007113:Immunity, Innate / Q000187:drug effects; D007601:Jugular Veins / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D003986:Dibenzocycloheptenes; D018809:Proliferating Cell Nuclear Antigen; C572387:skepinone-L; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Arterial-venous bypass; inflammation; intimal hyperplasia; p38 MAPK-inhibitor; vein graft