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 AngII (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.
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Research Article|
December 15 2008
Injury to rat carotid arteries causes time-dependent changes in gene expression in contralateral uninjured arteries
Amalia Forte;
*Excellence Research Centre for Cardiovascular Diseases, Department of Experimental Medicine, Second University of Naples, 80138 Naples, Italy
Correspondence: Dr Amalia Forte (email [email protected]).
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Mauro Finicelli;
Mauro Finicelli
*Excellence Research Centre for Cardiovascular Diseases, Department of Experimental Medicine, Second University of Naples, 80138 Naples, Italy
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Pasquale de Luca;
Pasquale de Luca
†BIOGEM s.c.a.r.l., 83031 Ariano Irpino, Italy
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Ina Nordström;
Ina Nordström
‡Department of Experimental Medical Science, Lund University, SE-221 84 Lund, Sweden
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Francesco Onorati;
Francesco Onorati
§Unit of Cardiac Surgery, University Magna Graecia, 88100 Catanzaro, Italy
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Cesare Quarto;
Cesare Quarto
∥Department of Cardiothoracic Sciences, Second University of Naples, 80138 Naples, Italy
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Pasquale Santè;
Pasquale Santè
∥Department of Cardiothoracic Sciences, Second University of Naples, 80138 Naples, Italy
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Attilio Renzulli;
Attilio Renzulli
§Unit of Cardiac Surgery, University Magna Graecia, 88100 Catanzaro, Italy
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Umberto Galderisi;
Umberto Galderisi
*Excellence Research Centre for Cardiovascular Diseases, Department of Experimental Medicine, Second University of Naples, 80138 Naples, Italy
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Liberato Berrino;
Liberato Berrino
*Excellence Research Centre for Cardiovascular Diseases, Department of Experimental Medicine, Second University of Naples, 80138 Naples, Italy
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Marisa de Feo;
Marisa de Feo
∥Department of Cardiothoracic Sciences, Second University of Naples, 80138 Naples, Italy
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Per Hellstrand;
Per Hellstrand
‡Department of Experimental Medical Science, Lund University, SE-221 84 Lund, Sweden
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Francesco Rossi;
Francesco Rossi
*Excellence Research Centre for Cardiovascular Diseases, Department of Experimental Medicine, Second University of Naples, 80138 Naples, Italy
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Maurizio Cotrufo;
Maurizio Cotrufo
∥Department of Cardiothoracic Sciences, Second University of Naples, 80138 Naples, Italy
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Antonino Cascino;
Antonino Cascino
*Excellence Research Centre for Cardiovascular Diseases, Department of Experimental Medicine, Second University of Naples, 80138 Naples, Italy
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Marilena Cipollaro
Marilena Cipollaro
*Excellence Research Centre for Cardiovascular Diseases, Department of Experimental Medicine, Second University of Naples, 80138 Naples, Italy
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Publisher: Portland Press Ltd
Received:
March 10 2008
Revision Received:
May 08 2008
Accepted:
June 03 2008
Accepted Manuscript online:
June 03 2008
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2009 Biochemical Society
2009
Clin Sci (Lond) (2009) 116 (2): 125–136.
Article history
Received:
March 10 2008
Revision Received:
May 08 2008
Accepted:
June 03 2008
Accepted Manuscript online:
June 03 2008
Citation
Amalia Forte, Mauro Finicelli, Pasquale de Luca, Ina Nordström, Francesco Onorati, Cesare Quarto, Pasquale Santè, Attilio Renzulli, Umberto Galderisi, Liberato Berrino, Marisa de Feo, Per Hellstrand, Francesco Rossi, Maurizio Cotrufo, Antonino Cascino, Marilena Cipollaro; Injury to rat carotid arteries causes time-dependent changes in gene expression in contralateral uninjured arteries. Clin Sci (Lond) 1 January 2009; 116 (2): 125–136. doi: https://doi.org/10.1042/CS20080080
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