Defective NOTCH signaling drives increased vascular smooth muscle cell apoptosis and contractile differentiation in bicuspid aortic valve aortopathy: a review of the evidence and future directions

Bicuspid aortic valve (BAV) disease remains the most common congenital cardiac disease and is associated with an increased risk of potentially fatal aortopathy including aortic aneurysm and dissection. Mutations in the NOTCH1 gene are one of only a few genetic anomalies identified in BAV disease; however evidence for defective NOTCH signaling, and its involvement in the characteristic histological changes of VSMC apoptosis and differentiation in ascending aortae of BAV patients is lacking. This review scrutinizes the evidence for the interactions of NOTCH signaling, cellular differentiation and apoptosis in the context of aortic VSMCs and provides focus for future research efforts in the diagnosis of BAV aortopathy and prevention of catastrophic complications through NOTCH signaling manipulation