Notch 1 pathway and EPCs in bicuspid aortic valve: is their interplay involved in the ascending aortic aneurysm onset?

Backgroud_AIM: Bicuspid aortic valve (BAV) is frequently associated with 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. Methods: To this aim,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), AAA complicated or not, were enrolled. Multiparametric flow cytometry analyses, plasma amount assessments, gene expressions, and tissue protein semiquantitative evaluations were also performed.Results: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. CONCLUSION: 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.