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  • Forte, A (author)

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

  • Article/chapterEnglish2005

Publisher, publication year, extent ...

  • 2005-06-03
  • S. Karger AG,2005

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:1a8a1b82-7531-47a7-962f-485545def431
  • https://lup.lub.lu.se/record/238691URI
  • https://doi.org/10.1159/000085379DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Galderisi, U (author)
  • De Feo, M (author)
  • Gomez, MariaLund University,Lunds universitet,Kärlfysiologi,Forskargrupper vid Lunds universitet,Vascular Physiology,Lund University Research Groups(Swepub:lu)mphy-mgo (author)
  • Esposito, S (author)
  • Sante, P (author)
  • Renzulli, A (author)
  • Agozzino, L (author)
  • Hellstrand, PerLund University,Lunds universitet,Kärlfysiologi,Forskargrupper vid Lunds universitet,Vascular Physiology,Lund University Research Groups(Swepub:lu)mphy-phe (author)
  • Berrino, L (author)
  • Cipollaro, M (author)
  • Cotrufo, M (author)
  • Rossi, F (author)
  • Cascino, A (author)
  • KärlfysiologiForskargrupper vid Lunds universitet (creator_code:org_t)

Related titles

  • In:Journal of Vascular Research: S. Karger AG42:3, s. 214-2251423-01351018-1172

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