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Maria Gomez

Maria Gomez

Professor

Maria Gomez

c-Myc antisense oligonucleotides preserve smooth muscle differentiation and reduce negative remodelling following rat carotid arteriotomy

Author

  • A Forte
  • U Galderisi
  • M De Feo
  • Maria Gomez
  • S Esposito
  • P Sante
  • A Renzulli
  • L Agozzino
  • Per Hellstrand
  • L Berrino
  • M Cipollaro
  • M Cotrufo
  • F Rossi
  • A Cascino

Summary, in English

Objectives: The vascular biology of restenosis is complex and not fully understood, thus explaining the lack of effective therapy for its prevention in clinical settings. The role of c-Myc in arteriotomy-induced stenosis, smooth muscle cell (SMC) differentiation and apoptosis was investigated in rat carotids applying full phosphorothioate antisense ( AS) oligonucleotides (ODNs). Methods: Carotid arteries from WKY rats were submitted to arteriotomy and to local application of ODNs through pluronic gel. Apoptosis ( deoxynucleotidyl transferase-mediated dUTP nick end-labelling), SMC differentiation (SM22 immunofluorescence) and vessel morphology and morphometry ( image analysis) were determined 2, 5 and 30 days after injury, respectively. Results: AS ODNs induced a 60% decrease of target c-Myc mRNA 4 h after surgery in comparison to control sense ( S) and scrambled ODN-treated carotids (p < 0.05). A significant 37 and 50% decrease in SM22 protein in the media of S ODN-treated and untreated carotids was detected when compared to uninjured contralateral arteries (p < 0.05). This reduction in SM22 expression was prevented in AS ODN-treated carotids. Stenosis was mainly due to adventitial constrictive remodelling. Lumen area in AS ODN-treated carotids was 35% greater than in control arteries 30 days after surgery (p < 0.05). TUNEL assay revealed increased apoptosis in AS ODN-treated carotids (p < 0.05). Conclusions: c-Myc AS ODNs reduce arteriotomy-induced negative remodelling. This is accompanied by maintained SMC differentiation and greater apoptosis. The combination of reduced c-Myc-induced proliferation and increased apoptosis may thus underlie the less severe remodelling upon treatment with c-Myc mRNA AS ODN.

Department/s

  • Vascular Physiology

Publishing year

2005

Language

English

Pages

214-225

Publication/Series

Journal of Vascular Research

Volume

42

Issue

3

Document type

Journal article

Publisher

Karger

Topic

  • Cardiac and Cardiovascular Systems

Keywords

  • antisense oligonucleotides
  • SM22
  • arteriotomy
  • c-Myc
  • stenosis
  • apoptosis
  • adventitia

Status

Published

Research group

  • Vascular Physiology

ISBN/ISSN/Other

  • ISSN: 1423-0135