Abstract
Neonates with coarctation of the aorta (CoA) combined with a bicuspid aortic valve (BAV) show significant structural differences compared to neonatal CoA patients with a normal tricuspid aortic valve (TAV). These effects are likely to change over time in response to growth. This study investigated proteomic differences between coarcted aortic tissue of BAV and TAV patients in children older than one month. Aortic tissue just proximal to the coarctation site was collected from 10 children (BAV; n=6, 1.9±1.7 years, TAV; n=4, 1.7±1.5 years, (mean ± SEM, P=0.92.) Tissue were snap frozen, proteins extracted, and the extracts used for proteomic and phosphoproteomic analysis using Tandem Mass Tag (TMT) analysis. A total of 1811 protein and 76 phosphoprotein accession numbers were detected, of which 40 proteins and 6 phosphoproteins were significantly differentially expressed between BAV and TAV patients. Several canonical pathways involved in inflammation demonstrated enriched protein expression, including acute phase response signalling, EIF2 signalling and macrophage production of IL12 and reactive oxygen species. Acute phase response signalling also demonstrated enriched phosphoprotein expression, as did Th17 activation. Other pathways with significantly enriched protein expression include degradation of superoxide radicals and several pathways involved in apoptosis. This work suggests that BAV CoA patients older than one month have an altered proteome consistent with changes in inflammation, apoptosis and oxidative stress compared to TAV CoA patients of the same age. There is no evidence of structural differences, suggesting the pathology associated with BAV evolves with age in paediatric CoA patients.
Highlights
One of the most common congenital cardiac abnormalities is coarctation of the aorta (CoA) [1]
This study focused on neonatal patients and demonstrated that the presence of bicuspid aortic valve (BAV) in neonatal CoA patients is associated with altered expression of proteins involved in elastin fibre formation and oxidative stress
A total of 76 phos‐ phorylated proteins were identified, some with multiple phosphorylation sites, resulting in 92 phosphorylation site matches. 6 phosphoproteins demonstrated significantly altered expression in BAV patients compared to tricuspid valve (TAV) patients; all 6 demonstrated increased phosphorylation in BAV patients (Fig. 1B, Table II)
Summary
One of the most common congenital cardiac abnormalities is coarctation of the aorta (CoA) [1]. Several studies have demonstrated that the risks are greater in CoA patients with BAV compared to CoA patients with the normal tricuspid valve (TAV) [6,7,8]. The co‐existence of BAV and CoA is known to alter aortic blood flow haemody‐ namics, and this may underlie the increased susceptibility of CoA patients with BAV to cardiovascular complications [9,10]. This study focused on neonatal patients (less than 3 weeks old) and demonstrated that the presence of BAV in neonatal CoA patients is associated with altered expression of proteins involved in elastin fibre formation and oxidative stress. In older CoA patients, there will have been more time for aortic remodelling to occur in response to the altered blood flow haemodynamics, and this will likely effect protein expression. The current study compares the proteome of CoA patients with and without BAV in paediatric patients older than one month, providing a unique insight into how the proteomic changes associated with BAV evolve in an older group of CoA patients
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