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Clinical Science (2008) Immediate Publication, doi:10.1042/CS20080080
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Injury to rat carotids causes time-dependent changes in gene expression in contralateral uninjured arteries
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Amalia Forte, Mauro Finicelli, Pasquale De Luca, Ina Nordstrom, Francesco Onorati, Cesare Quarto, Pasquale Santè, Attilio Renzulli, Umberto Galderisi, Liberato Berrino, Marisa De Feo, Per Hellstrand, Francesco Rossi, Maurizio Cotrufo, Antonino Cascino and Marilena Cipollaro
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Dept. of Experimental Medicine, Second University of Naples, Naples 80138, Italy. amalia.forte@unina2.it
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Vascular surgery aimed at stenosis removal induces local reactions often leading to restenosis. While extensive analysis has been focused on pathways activated in injured arteries, little attention has been devoted to associated systemic vascular reactions. Aim of this study was to analyse changes occurring in contralateral uninjured rat carotids in the acute phase following unilateral injury. WKY rats were submitted to unilateral carotid arteriotomy. Contralateral uniunjured carotids were harvested from 4 hrs to 7 days after injury. Carotids were also harvested from sham-operated rats and from 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 and verified at protein level by Western Blot. 1011 genes were differentially regulated in contralateral uninjured carotids from 4 hrs to 7 days after arteriotomy (p<0.0001, fold-change ≥2) and were classified in 19 gene ontology functional categories. To a lesser extent, mRNA variations occurred also in carotids of sham-operated rats. Among the changes, up-regulation of members of the Renin-Angiotensin System was detected, with possible implications for vasocompensative mechanisms induced by arteriotomy. In particular, a selective increase of the N-domain Angiotensin Converting Enzyme 69-kDa isoform, and not the classical somatic 195 kDa isoform, was highlighted in contralateral uninjured carotids, suggesting that this 69-kDa isoenzyme could influence the local Angiotensin II production. In conclusion, systemic reactions to injury occur in the vasculature, with potential clinical relevance and suggesting caution in the choice of control during experimental design in vivo.
doi:10.1042/CS20080080
Received 10 March 2008/8 May 2008; Accepted 3 June 2008
Published as Immediate Publication 3 June 2008
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