Bis (Aspirinato) Zinc (II) Complex Successfully Inhibits Carotid Arterial Neointima Formation after Balloon-injury in Rats

Péter Hegedűs, Sevil Korkmaz, T. Radovits, Harald Schmidt, Shiliang Li, Yutaka Yoshikawa, Hiroyuki Yasui, B. Merkely, Matthias Karck, G. Szabó

Research output: Contribution to journalArticle

4 Citations (Scopus)

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) 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.

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.

Original languageEnglish
Pages (from-to)533-539
Number of pages7
JournalCardiovascular Drugs and Therapy
Volume28
Issue number6
DOIs
Publication statusPublished - Dec 9 2014

Fingerprint

Neointima
Wounds and Injuries
Messenger RNA
Smooth Muscle
Common Carotid Artery
Matrix Metalloproteinase 9
Proliferating Cell Nuclear Antigen
Transforming Growth Factors
Angioplasty
Carotid Arteries
Aspirin
Smooth Muscle Myocytes
Zinc
Actins
Histology
Pathologic Constriction
Collagen
Therapeutics
Arteries
Immunohistochemistry

Keywords

  • Balloon-injury
  • Bis (aspirinato) zinc
  • Neointima
  • Restenosis

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Cardiology and Cardiovascular Medicine
  • Pharmacology
  • Medicine(all)

Cite this

Bis (Aspirinato) Zinc (II) Complex Successfully Inhibits Carotid Arterial Neointima Formation after Balloon-injury in Rats. / Hegedűs, Péter; Korkmaz, Sevil; Radovits, T.; Schmidt, Harald; Li, Shiliang; Yoshikawa, Yutaka; Yasui, Hiroyuki; Merkely, B.; Karck, Matthias; Szabó, G.

In: Cardiovascular Drugs and Therapy, Vol. 28, No. 6, 09.12.2014, p. 533-539.

Research output: Contribution to journalArticle

Hegedűs, Péter ; Korkmaz, Sevil ; Radovits, T. ; Schmidt, Harald ; Li, Shiliang ; Yoshikawa, Yutaka ; Yasui, Hiroyuki ; Merkely, B. ; Karck, Matthias ; Szabó, G. / Bis (Aspirinato) Zinc (II) Complex Successfully Inhibits Carotid Arterial Neointima Formation after Balloon-injury in Rats. In: Cardiovascular Drugs and Therapy. 2014 ; Vol. 28, No. 6. pp. 533-539.
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AU - Hegedűs, Péter

AU - Korkmaz, Sevil

AU - Radovits, T.

AU - Schmidt, Harald

AU - Li, Shiliang

AU - Yoshikawa, Yutaka

AU - Yasui, Hiroyuki

AU - Merkely, B.

AU - Karck, Matthias

AU - Szabó, G.

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N2 - 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) 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.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.

AB - 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) 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.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.

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KW - Neointima

KW - Restenosis

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