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c-Myc antisense oli...
c-Myc antisense oligonucleotides preserve smooth muscle differentiation and reduce negative remodelling following rat carotid arteriotomy
- Article/chapterEnglish2005
Publisher, publication year, extent ...
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2005-06-03
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S. Karger AG,2005
Numbers
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LIBRIS-ID:oai:lup.lub.lu.se:1a8a1b82-7531-47a7-962f-485545def431
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https://lup.lub.lu.se/record/238691URI
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https://doi.org/10.1159/000085379DOI
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
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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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Galderisi, U
(author)
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De Feo, M
(author)
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Gomez, MariaLund University,Lunds universitet,Kärlfysiologi,Forskargrupper vid Lunds universitet,Vascular Physiology,Lund University Research Groups(Swepub:lu)mphy-mgo
(author)
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Esposito, S
(author)
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Sante, P
(author)
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Renzulli, A
(author)
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Agozzino, L
(author)
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Hellstrand, PerLund University,Lunds universitet,Kärlfysiologi,Forskargrupper vid Lunds universitet,Vascular Physiology,Lund University Research Groups(Swepub:lu)mphy-phe
(author)
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Berrino, L
(author)
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Cipollaro, M
(author)
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Cotrufo, M
(author)
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Rossi, F
(author)
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Cascino, A
(author)
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KärlfysiologiForskargrupper vid Lunds universitet
(creator_code:org_t)
Related titles
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In:Journal of Vascular Research: S. Karger AG42:3, s. 214-2251423-01351018-1172
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Forte, A
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Galderisi, U
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De Feo, M
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Gomez, Maria
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Esposito, S
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Sante, P
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Renzulli, A
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Agozzino, L
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Hellstrand, Per
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Berrino, L
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Cipollaro, M
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Cotrufo, M
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Rossi, F
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Cascino, A
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
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Journal of Vascu ...
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Lund University