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Injury to rat carotid arteries causes time-dependent changes in gene expression in contralateral uninjured arteries

Forte, Amalia; Finicelli, Mauro; De Luca, Pasquale; Nordström, Ina LU ; Onorati, Francesco; Quarto, Cesare; Sante, Pasquale; Renzulli, Attilio; Galderisi, Umberto and Berrino, Liberato, et al. (2009) In Clinical Science 116(1-2). p.125-136
Abstract
Vascular surgery aimed at stenosis removal induces local reactions often leading to restenosis. Although extensive analysis has been focused on pathways activated in injured arteries, little attention has been devoted to associated systemic vascular reactions. The aim of the present study was to analyse changes occurring in contralateral uninjured rat carotid arteries in the acute phase following unilateral injury. WKY (Wistar-Kyoto) rats were subjected to unilateral carotid arteriotomy. Contralateral uninjured carotid arteries were harvested from 4 h to 7 days after injury. Carotid arteries were also harvested from sham-operated rats and uninjured rats. Carotid morphology and morphometry were examined. Affymetrix microarrays were used for... (More)
Vascular surgery aimed at stenosis removal induces local reactions often leading to restenosis. Although extensive analysis has been focused on pathways activated in injured arteries, little attention has been devoted to associated systemic vascular reactions. The aim of the present study was to analyse changes occurring in contralateral uninjured rat carotid arteries in the acute phase following unilateral injury. WKY (Wistar-Kyoto) rats were subjected to unilateral carotid arteriotomy. Contralateral uninjured carotid arteries were harvested from 4 h to 7 days after injury. Carotid arteries were also harvested from sham-operated rats and uninjured rats. Carotid morphology and morphometry were examined. Affymetrix microarrays were used for differential analysis of gene expression. A subset of data was validated by real-time RT-PCR (reverse transcription-PCR) and verified at the protein level by Western blotting. A total of 1011 genes were differentially regulated in contralateral uninjured carotid arteries from 4 h to 7 days after arteriotomy (P < 0.0001; fold change, >= 2) and were classified into 19 gene ontology functional categories. To a lesser extent, mRNA variations also occurred in carotid arteries of sham-operated rats. Among the changes, up-regulation of members of the RAS (renin-angiotensin system) was detected, with possible implications for vasocompensative mechanisms induced by arteriotomy. In particular, a selective increase in the 69 kDa isoform of the N-domain of ACE (angiotensin-converting enzyme), and not the classical somatic 195 kDa isoform, was observed in contralateral uninjured carotid arteries, suggesting that this 69 kDa isoenzyme could influence local Angll (angiotensin II) production. In conclusion, systemic reactions to injury occur in the vasculature, with potential clinical relevance, and suggest that caution is needed in the choice of controls during experimental design in vivo. (Less)
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Contribution to journal
publication status
published
subject
keywords
renin-angiotensin, remodelling, microarray, blood flow, inflammation, system, vascular injury
in
Clinical Science
volume
116
issue
1-2
pages
125 - 136
publisher
Portland Press
external identifiers
  • wos:000262212900014
  • scopus:60549085776
ISSN
1470-8736
DOI
10.1042/CS20080080
language
English
LU publication?
yes
id
bcdbcde7-7cfa-4838-b9b8-7a814da3a245 (old id 1312841)
date added to LUP
2009-03-18 09:03:30
date last changed
2017-01-01 05:08:44
@article{bcdbcde7-7cfa-4838-b9b8-7a814da3a245,
  abstract     = {Vascular surgery aimed at stenosis removal induces local reactions often leading to restenosis. Although extensive analysis has been focused on pathways activated in injured arteries, little attention has been devoted to associated systemic vascular reactions. The aim of the present study was to analyse changes occurring in contralateral uninjured rat carotid arteries in the acute phase following unilateral injury. WKY (Wistar-Kyoto) rats were subjected to unilateral carotid arteriotomy. Contralateral uninjured carotid arteries were harvested from 4 h to 7 days after injury. Carotid arteries were also harvested from sham-operated rats and uninjured rats. Carotid morphology and morphometry were examined. Affymetrix microarrays were used for differential analysis of gene expression. A subset of data was validated by real-time RT-PCR (reverse transcription-PCR) and verified at the protein level by Western blotting. A total of 1011 genes were differentially regulated in contralateral uninjured carotid arteries from 4 h to 7 days after arteriotomy (P &lt; 0.0001; fold change, &gt;= 2) and were classified into 19 gene ontology functional categories. To a lesser extent, mRNA variations also occurred in carotid arteries of sham-operated rats. Among the changes, up-regulation of members of the RAS (renin-angiotensin system) was detected, with possible implications for vasocompensative mechanisms induced by arteriotomy. In particular, a selective increase in the 69 kDa isoform of the N-domain of ACE (angiotensin-converting enzyme), and not the classical somatic 195 kDa isoform, was observed in contralateral uninjured carotid arteries, suggesting that this 69 kDa isoenzyme could influence local Angll (angiotensin II) production. In conclusion, systemic reactions to injury occur in the vasculature, with potential clinical relevance, and suggest that caution is needed in the choice of controls during experimental design in vivo.},
  author       = {Forte, Amalia and Finicelli, Mauro and De Luca, Pasquale and Nordström, Ina and Onorati, Francesco and Quarto, Cesare and Sante, Pasquale and Renzulli, Attilio and Galderisi, Umberto and Berrino, Liberato and De Feo, Marisa and Hellstrand, Per and Rossi, Francesco and Cotrufo, Maurizio and Cascino, Antonino and Cipollaro, Marilena},
  issn         = {1470-8736},
  keyword      = {renin-angiotensin,remodelling,microarray,blood flow,inflammation,system,vascular injury},
  language     = {eng},
  number       = {1-2},
  pages        = {125--136},
  publisher    = {Portland Press},
  series       = {Clinical Science},
  title        = {Injury to rat carotid arteries causes time-dependent changes in gene expression in contralateral uninjured arteries},
  url          = {http://dx.doi.org/10.1042/CS20080080},
  volume       = {116},
  year         = {2009},
}