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Deregulation of Notch1 pathway and circulating endothelial progenitor cell (EPC) number in patients with bicuspid aortic valve with and without ascending aorta aneurysm.

ABSTRACT: Bicuspid aortic valve (BAV) is frequently associated with the development of ascending aortic aneurysm, even if the underlying mechanisms remain to be clarified. Here, we investigated if a deregulation of Notch1 signaling pathway and endothelial progenitor cells (EPCs) number is associated with BAV disease and an early ascending aortic aneurysm (AAA) onset. For this purpose, 70 subjects with BAV (M/F 50/20; mean age: 58.8?±?14.8 years) and 70 subjects with tricuspid aortic valve (TAV) (M/F 35/35; mean age: 69.1?±?12.8 years) and AAA complicated or not, were included. Interestingly, patients with AAA showed a significant increase in circulating Notch1 levels and EPC number than subjects without AAA. However, circulating Notch1 levels and EPC number were significantly lower in BAV subjects than TAV patients either in the presence or absence of AAA. Finally, Notch pathway was activated to a greater extent in aortic aneurysmatic portions with respect to healthy aortic fragments in both BAV and TAV patients. However, the expression of genes encoding components and ligands of Notch pathway in aortic tissues was significantly lower in BAV than TAV subjects. Our study demonstrates that BAV subjects are characterized by a significant decrease in both tissue and circulating levels of Notch pathway, and in blood EPC number than TAV patients, either in presence or absence of AAA disease.

SUBMITTER: Balistreri CR

PROVIDER: S-EPMC6138685 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Deregulation of Notch1 pathway and circulating endothelial progenitor cell (EPC) number in patients with bicuspid aortic valve with and without ascending aorta aneurysm.

Balistreri Carmela R CR Crapanzano Floriana F Schirone Leonardo L Allegra Alberto A Pisano Calogera C Ruvolo Giovanni G Forte Maurizio M Greco Ernesto E Cavarretta Elena E Marullo Antonino G M AGM Sciarretta Sebastiano S Frati Giacomo G

Scientific reports 20180914 1

Bicuspid aortic valve (BAV) is frequently associated with the development of ascending aortic aneurysm, even if the underlying mechanisms remain to be clarified. Here, we investigated if a deregulation of Notch1 signaling pathway and endothelial progenitor cells (EPCs) number is associated with BAV disease and an early ascending aortic aneurysm (AAA) onset. For this purpose, 70 subjects with BAV (M/F 50/20; mean age: 58.8 ± 14.8 years) and 70 subjects with tricuspid aortic valve (TAV) (M/F 35/35 ...[more]

PMID: 30218064

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Project description:BACKGROUND:Bicuspid aortic valve (BAV) disease is the most common congenital cardiac abnormality affecting 1-2% of the population and is associated with a significantly increased risk of ascending aortic aneurysm. However, predicting which patients will develop aneurysms remains a challenge. This pilot study aimed to identify candidate plasma biomarkers for monitoring ascending aortic diameter and predicting risk of future aneurysm in BAV patients. METHODS:Plasma samples were collected pre-operatively from BAV patients undergoing aortic valve surgery. Maximum ascending aortic diameter was measured on pre-operative transoesophageal echocardiography. Maximum diameter???45 mm was classified as aneurysmal. Sequential Window Acquisition of all THeoretical Mass Spectra (SWATH-MS), an advanced mass spectrometry technique, was used to identify and quantify all proteins within the samples. Protein abundance and aortic diameter were correlated using logistic regression. Levene's test was used to identify proteins demonstrating low abundance variability in the aneurysmal patients (consistent expression in disease), and high variability in the non-aneurysmal patients (differential expression between 'at risk' and not 'at risk' patients). RESULTS:Fifteen plasma samples were collected (seven non-aneurysmal and 8 aneurysmal BAV patients). The mean age of the patients was 55.5 years and the majority were female (10/15, 67%). Four proteins (haemoglobin subunits alpha, beta and delta and mannan-binding lectin serine protease) correlated significantly with maximal ascending aortic diameter (p?<?0.05, r?=?0.5-0.6). Five plasma proteins demonstrated significantly lower variability in the aneurysmal group and may indicate increased risk of aneurysm in non-aneurysmal patients (DNA-dependent protein kinase catalytic subunit, lumican, tetranectin, gelsolin and cartilage acidic protein 1). A further 7 proteins were identified only in the aneurysmal group (matrin-3, glucose-6-phosphate isomerase, coactosin-like protein, peptidyl-prolyl cis-trans isomerase A, golgin subfamily B member 1, myeloperoxidase and 2'-deoxynucleoside 5'-phosphate N-hydrolase 1). CONCLUSIONS:This study is the first to identify candidate plasma biomarkers for predicting aortic diameter and risk of future aneurysm in BAV patients. It provides valuable pilot data and proof of principle that could be used to design a large-scale prospective investigation. Ultimately, a more affordable 'off-the-shelf' follow-on blood assay could then be developed in place of SWATH-MS, for use in the healthcare setting.

Project description:BackgroundAlthough a bicuspid aortic valve (BAV) is known to be associated with progressive ascending aortic dilatation, the fate of the residual aorta after aortic valve and ascending aorta surgery is unknown. We reviewed surgical outcomes and explored serial changes in the size of the sinus of Valsalva (SOV) and distal ascending aorta (DAAo) in 89 patients with a BAV undergoing aortic valve replacement (AVR) and graft replacement (GR) of the ascending aorta.MethodsWe retrospectively examined patients who underwent AVR and GR of the ascending aorta for BAV-and related disease and thoracic aortic dilatation at our institution between January 2009 and December 2018. Patients who underwent AVR alone or required intervention for the aortic root and aortic arch and patients with connective tissue diseases were excluded. Aortic diameters were examined using computed tomography (CT). Late CT more than 1 year after surgery was performed in 69 patients (78%) with a mean follow-up of 4.9±2.8 years.ResultsThe surgical indication for aortic valve etiology was stenosis in 61 patients (69%), regurgitation in 10 (11%), and mixed in 18 (20%). Preoperative maximum short diameters of the ascending aorta, SOV, and DAAo were 47.3±4.7, 36.0±5.2, and 37.2±3.6 mm, respectively. The diameter of the SOV increased non-significantly by 0.08±0.45 mm per year [95% confidence interval (CI): -0.12 to 0.11, P=0.150], while that of the DAAo increased significantly by 0.11±0.40 mm per year (95% CI: 0.02-0.21, P=0.005). One patient required reoperation 6 years postoperatively due to a pseudo-aneurysm at the proximal anastomotic site. No patient required reoperation due to progressive dilatation of the residual aorta. According to the Kaplan-Meier analysis, the long-term survival rates were 98.9%, 98.9%, and 92.7% at 1, 5, and 10 years postoperatively, respectively.ConclusionsRapid dilatation of the residual aorta rarely occurred in patients with a BAV who underwent AVR and GR of the ascending aorta in the mid-term follow-up. For selected patients with a surgical indication for ascending aortic dilatation, simple AVR and GR of the ascending aorta may be sufficient surgical options.

Dataset Information

Deregulation of Notch1 pathway and circulating endothelial progenitor cell (EPC) number in patients with bicuspid aortic valve with and without ascending aorta aneurysm.

Publications

Deregulation of Notch1 pathway and circulating endothelial progenitor cell (EPC) number in patients with bicuspid aortic valve with and without ascending aorta aneurysm.

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