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- Title
Bis (Aspirinato) Zinc (II) Complex Successfully Inhibits Carotid Arterial Neointima Formation after Balloon-injury in Rats.
- Authors
Hegedűs, Péter; Korkmaz, Sevil; Radovits, Tamás; Schmidt, Harald; Li, Shiliang; Yoshikawa, Yutaka; Yasui, Hiroyuki; Merkely, Béla; Karck, Matthias; Szabó, Gábor
- Abstract
Purpose: 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) -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) -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) 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). 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) treatment compared to the untreated and ASA-groups. Conclusion: 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.
- Subjects
CAROTID artery diseases; ANGIOPLASTY; PLASTIC surgery complications; CORONARY restenosis; LABORATORY rats
- Publication
Cardiovascular Drugs & Therapy, 2014, Vol 28, Issue 6, p533
- ISSN
0920-3206
- Publication type
Article
- DOI
10.1007/s10557-014-6549-2