title: Bis (aspirinato) zinc (II) complex successfully inhibits carotid arterial neointima formation after balloon-injury in rats.
abstract: OBJECTIVE
  Neointima formation following angioplasty is a serious consequence of endothelial damage in arteries. Inflammatory mediators and lack of endothelial regulatory mechanisms lead to migration and proliferation of smooth-muscle cells and thus to restenosis. This study examines the effect of the novel bis (aspirinato) zinc (II) complex on neointima formation in a rat model of carotid balloon-injury.
  
  
  METHODS
  Rats underwent balloon-injury of the right common carotid artery, then received PEG400 vehicle (untreated-group), acetylsalicylic-acid (ASA-group), zinc-chloride (Zn-group) and bis (aspirinato) zinc (II) complex (Zn(ASA) 2-group) orally for 18 consecutive days. From harvested carotid arteries, histology, immunohistochemistry and mRNA expression analysis were performed.
  
  
  RESULTS
  Compared to the untreated-group, Zn (ASA) 2-treatment significantly lowered stenosis ratio (54.0 ± 5.8% to 25.5 ± 3.9%) and reduced neointima/media ratio (1.5 ± 0.2 to 0.5 ± 0.1). Significantly higher alpha smooth muscle actin mRNA and protein expression were measured after Zn (ASA)2 and Zn-treatment in comparison with the untreated and ASA-groups while the expression of matrix-metalloproteinase-9 was significantly higher in these groups compared to Zn (ASA)2. The presence of collagen in media was significantly decreased in all treated groups. mRNA expressions of nuclear factor kappa-b, transforming growth-factor-β and proliferating cell nuclear antigen were significantly down-regulated, whereas a20 was up-regulated by Zn (ASA)2 treatment compared to the untreated and ASA-groups.
  
  
  CONCLUSIONS
  This study proves the effectivity of the novel bis (aspirinato) zinc complex in reducing neointima formation and restenosis after balloon-injury and supports the hypothesis that inhibition of smooth-muscle transformation/proliferation plays a key role in the prevention of restenosis.
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, INF 326, Heidelberg, 69120, Germany, phegedues@gmail.com.
authors.forename: Péter
authors.initials: P
authors.lastname: Hegedűs
authors.forename: Sevil
authors.initials: S
authors.lastname: Korkmaz
authors.forename: Tamás
authors.initials: T
authors.lastname: Radovits
authors.forename: Harald
authors.initials: H
authors.lastname: Schmidt
authors.forename: Shiliang
authors.initials: S
authors.lastname: Li
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yasui
authors.forename: Béla
authors.initials: B
authors.lastname: Merkely
authors.forename: Matthias
authors.initials: M
authors.lastname: Karck
authors.forename: Gábor
authors.initials: G
authors.lastname: Szabó
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D058426:Neointima / Q000188:drug therapy* / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003094:Collagen; D020780:Matrix Metalloproteinase 9; D015032:Zinc