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J. Clin. Med. 2019, 8(4), 517; https://doi.org/10.3390/jcm8040517

Bicuspid Aortic Valve Alters Aortic Protein Expression Profile in Neonatal Coarctation Patients

1
Bristol Heart Institute, Research Floor Level 7, Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK
2
Department of Congenital Heart Disease, King David Building, Upper Maudlin Street, Bristol BS2 8JB, UK
3
Proteomics Facility, University of Bristol, Bristol BS8 1TD, UK
*
Author to whom correspondence should be addressed.
Received: 12 March 2019 / Revised: 2 April 2019 / Accepted: 12 April 2019 / Published: 16 April 2019
(This article belongs to the Section Cardiology)
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Abstract

Coarctation of the aorta is a form of left ventricular outflow tract obstruction in paediatric patients that can be presented with either bicuspid (BAV) or normal tricuspid (TAV) aortic valve. The congenital BAV is associated with hemodynamic changes and can therefore trigger different molecular remodelling in the coarctation area. This study investigated the proteomic and phosphoproteomic changes associated with BAV for the first time in neonatal coarctation patients. Aortic tissue was collected just proximal to the coarctation site from 23 neonates (BAV; n = 10, TAV; n = 13) that were matched for age (age range 4–22 days). Tissue from half of the patients was frozen and used for proteomic and phosphoproteomic analysis whilst the remaining tissue was formalin fixed and used for analysis of elastin content using Elastic Van-Gieson (EVG) staining. A total of 1796 protein and 75 phosphoprotein accession numbers were detected, of which 34 proteins and one phosphoprotein (SSH3) were differentially expressed in BAV patients compared to TAV patients. Ingenuity Pathway Analysis identified the formation of elastin fibres as a significantly enriched function (p = 1.12 × 10−4) due to the upregulation of EMILIN-1 and the downregulation of TNXB. Analysis of paraffin sections stained with EVG demonstrated increased elastin content in BAV patients. The proteomic/phosphoproteomic analysis also suggested changes in inositol signalling pathways and reduced expression of the antioxidant SOD3. This work demonstrates for the first time that coarcted aortic tissue in neonatal BAV patients has an altered proteome/phosphoproteome consistent with observed structural vascular changes when compared to TAV patients. View Full-Text
Keywords: aortic coarctation; bicuspid aortic valve; congenital heart disease aortic coarctation; bicuspid aortic valve; congenital heart disease
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Skeffington, K.L.; Bond, A.R.; Abdul-Ghani, S.; Iacobazzi, D.; Kang, S.-L.; Heesom, K.J.; Wilson, M.C.; Ghorbel, M.; Stoica, S.; Martin, R.; Suleiman, M.S.; Caputo, M. Bicuspid Aortic Valve Alters Aortic Protein Expression Profile in Neonatal Coarctation Patients. J. Clin. Med. 2019, 8, 517.

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