Journal ArticleDOI
Early cell changes and TGFβ pathway alterations in the aortopathy associated with bicuspid aortic valve stenosis
Amalia Forte,Alessandro Della Corte,Mario Grossi,Ciro Bancone,Raffaela Provenzano,Mauro Finicelli,Marisa De Feo,Luca Salvatore De Santo,Gianantonio Nappi,Maurizio Cotrufo,Umberto Galderisi,Marilena Cipollaro +11 more
TLDR
The results suggest that changes in SMC phenotype and, likely, MF differentiation, occur early in the aortopathy associated with valve stenosis, while other changes reported could be influenced by haemodynamics.Abstract:
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.read more
Citations
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Journal ArticleDOI
Valve-Related Hemodynamics Mediate Human Bicuspid Aortopathy: Insights From Wall Shear Stress Mapping.
David G. Guzzardi,Alex J. Barker,Pim van Ooij,Pim van Ooij,S. Chris Malaisrie,Jyothy Puthumana,Darrell D. Belke,Holly E.M. Mewhort,Daniyil A. Svystonyuk,Sean Kang,Subodh Verma,Jeremy D. Collins,James C. Carr,Robert O. Bonow,Michael Markl,James D. Thomas,Patrick M. McCarthy,Paul W.M. Fedak,Paul W.M. Fedak +18 more
TL;DR: Regions of increased WSS correspond with ECM dysregulation and elastic fiber degeneration in the ascending aorta of BAV patients, implicating valve-related hemodynamics as a contributing factor in the development of aortopathy.
Journal ArticleDOI
Bicuspid Aortic Valve: Identifying Knowledge Gaps and Rising to the Challenge From the International Bicuspid Aortic Valve Consortium (BAVCon)
Hector I. Michelena,Siddharth K. Prakash,Alessandro Della Corte,Malenka M. Bissell,Nandan S. Anavekar,Patrick Mathieu,Yohan Bossé,Giuseppe Limongelli,Eduardo Bossone,D. Woodrow Benson,Patrizio Lancellotti,Eric M. Isselbacher,Eric M. Isselbacher,Maurice Enriquez-Sarano,Thoralf M. Sundt,Philippe Pibarot,Artur Evangelista,Dianna M. Milewicz,Simon C. Body,Simon C. Body,Simon C. Body +20 more
TL;DR: This review describes the current knowledge of BAV, and proposes a roadmap to discovery based on current imaging, molecular biology, and genetic tools, recognizing their advantages and limitations.
Journal ArticleDOI
The American Association for Thoracic Surgery consensus guidelines on bicuspid aortic valve-related aortopathy: Full online-only version
Michael A. Borger,Paul W.M. Fedak,Elizabeth H. Stephens,Thomas G. Gleason,Evaldas Girdauskas,John S. Ikonomidis,Ali Khoynezhad,Samuel C. Siu,Subodh Verma,Michael D. Hope,Duke E. Cameron,Donald F. Hammer,Joseph S. Coselli,Marc R. Moon,Thoralf M. Sundt,Alex J. Barker,Michael Markl,Alessandro Della Corte,Hector I. Michelena,John A. Elefteriades +19 more
TL;DR: Current guidelines cover all major aspects of bicuspid aortic valve aortopathy, including natural history, phenotypic expression, histology and molecular pathomechanisms, imaging, indications for surgery, surveillance, and follow-up, and recommendations for future research.
Journal ArticleDOI
Aortic Dilatation in Patients With Bicuspid Aortic Valve.
TL;DR: A brief comprehensive review of the current knowledge on Bicuspid aortic valve (BAV) aortopathy regarding clinical definitions, epidemiology, natural course, and pathophysiology, as well as hemodynamic and clinically significant aspects on the basis of the limited data available is provided in this article.
Journal ArticleDOI
Phenotypic modulation of intima and media smooth muscle cells in fatal cases of coronary artery lesion
Hiroyuki Hao,Giulio Gabbiani,Edoardo Camenzind,Marc Bacchetta,Renu Virmani,Marie-Luce Bochaton-Piallat +5 more
TL;DR: Intimal SMCs of all situations exhibit a phenotypic profile, suggesting that they have modulated into myofibroblasts (MFs), and the high accumulation of alpha-SMA-positive MFs in erosions compared with stable plaques correlates with the higher appearance of thrombotic complications in this situation.
References
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