Previous studies on BAV (bicuspid aortic valve)-related aortopathy, whose aetiology is still debated, have focused mainly on severe dilatations. In the present study, we aimed to detect earlier signs of aortopathy. Specimens were collected from the ‘concavity’ (lesser curvature) and the ‘convexity’ (greater curvature) of mildly dilated AAs (ascending aortas; diameter ≤4 cm) with stenotic TAV (tricuspid aortic valve) or BAV and from donor normal aortas. Specimens were submitted to morphometry, immunohistochemistry and differential gene-expression analysis, focusing on SMC (smooth muscle cell) phenotype, remodelling, MF (myofibroblast) differentiation and TGFβ (transforming growth factor β) pathway. Smoothelin and myocardin mRNAs decreased in all the samples from patients, with the exception of those from BAV convexity, where a change in orientation of smoothelin-positive SMCs and an increase of α-SMA (α-smooth muscle actin) mRNA occurred. Dilated aortas from BAV and TAV patients showed both shared and distinct alterations concerning the TGFβ pathway, including an increased TGFβ and TGFβR2 (TGFβ receptor 2) expression in both groups and a decreased TGFβR1 expression in BAV samples only. Despite a decrease of the mRNA coding for the ED-A (extra domain-A) isoform of FN (fibronectin) in the BAV convexity, the onset of the expression of the corresponding protein in the media was observed in dilated aortas, whereas the normal media from donors was negative for this isoform. This discrepancy could be related to modifications in the intima, normally expressing ED-A FN and showing an altered structure in mild aortic dilatations in comparison with donor aorta. Our results suggest that changes in SMC phenotype and, likely, MF differentiation, occur early in the aortopathy associated with valve stenosis. The defective expression of TGFβR1 in BAV might be a constitutive feature, while other changes we reported could be influenced by haemodynamics.
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Research Article|
September 26 2012
Early cell changes and TGFβ pathway alterations in the aortopathy associated with bicuspid aortic valve stenosis
Amalia Forte;
Amalia Forte
*Department of Experimental Medicine, Second University of Naples, Naples, Italy
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Alessandro Della Corte;
†Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Naples, Italy
Correspondence: Dr Alessandro Della Corte (email [email protected]).
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Mario Grossi;
Mario Grossi
*Department of Experimental Medicine, Second University of Naples, Naples, Italy
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Ciro Bancone;
Ciro Bancone
†Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Naples, Italy
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Raffaela Provenzano;
Raffaela Provenzano
†Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Naples, Italy
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Mauro Finicelli;
Mauro Finicelli
*Department of Experimental Medicine, Second University of Naples, Naples, Italy
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Marisa De Feo;
Marisa De Feo
†Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Naples, Italy
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Luca S. De Santo;
Luca S. De Santo
†Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Naples, Italy
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Gianantonio Nappi;
Gianantonio Nappi
†Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Naples, Italy
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Maurizio Cotrufo;
Maurizio Cotrufo
†Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Naples, Italy
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Umberto Galderisi;
Umberto Galderisi
*Department of Experimental Medicine, Second University of Naples, Naples, Italy
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Marilena Cipollaro
Marilena Cipollaro
*Department of Experimental Medicine, Second University of Naples, Naples, Italy
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Publisher: Portland Press Ltd
Received:
June 18 2012
Revision Received:
July 19 2012
Accepted:
August 02 2012
Accepted Manuscript online:
August 02 2012
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2013 Biochemical Society
2013
Clin Sci (Lond) (2013) 124 (2): 97–108.
Article history
Received:
June 18 2012
Revision Received:
July 19 2012
Accepted:
August 02 2012
Accepted Manuscript online:
August 02 2012
Citation
Amalia Forte, Alessandro Della Corte, Mario Grossi, Ciro Bancone, Raffaela Provenzano, Mauro Finicelli, Marisa De Feo, Luca S. De Santo, Gianantonio Nappi, Maurizio Cotrufo, Umberto Galderisi, Marilena Cipollaro; Early cell changes and TGFβ pathway alterations in the aortopathy associated with bicuspid aortic valve stenosis. Clin Sci (Lond) 1 January 2013; 124 (2): 97–108. doi: https://doi.org/10.1042/CS20120324
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