Enlightening the Association between Bicuspid Aortic Valve and Aortopathy

Abstract

Bicuspid aortic valve (BAV) patients have an increased incidence of developing aortic dilation. Despite its importance, the pathogenesis of aortopathy in BAV is still largely undetermined. Nowadays, intense focus falls both on BAV morphology and progression of valvular dysfunction and on the development of aortic dilation. However, less is known about the relationship between aortic valve morphology and aortic dilation. A better understanding of the molecular pathways involved in the homeostasis of the aortic wall, including the extracellular matrix, the plasticity of the vascular smooth cells, TGFβ signaling, and epigenetic dysregulation, is key to enlighten the mechanisms underpinning BAV-aortopathy development and progression. To date, there are two main theories on this subject, i.e., the genetic and the hemodynamic theory, with an ongoing debate over the pathogenesis of BAV-aortopathy. Furthermore, the lack of early detection biomarkers leads to challenges in the management of patients affected by BAV-aortopathy. Here, we critically review the current knowledge on the driving mechanisms of BAV-aortopathy together with the current clinical management and lack of available biomarkers allowing for early detection and better treatment optimization.

Utilizing wall shear stress as a clinical biomarker for bicuspid valve-associated aortopathy

“…Matrix metalloproteases (MMP) are also differentially expressed across different aortic sites in BAV, with higher levels of MMP-2 and tissue inhibitor of metalloprotease (TIMP)-3 observed in the concavity of the ascending aorta (29). When comparing convex and concave portions of dilated aortas of BAV patients, similar trends are noted in microRNA expression of these proteins (21,30). These findings strongly support the hypothesis that bicuspid aortopathy is influenced by active cellular processes.…”

“…However, the fiber architecture is similar to that of the normal aorta (24). It has been shown that bicuspid aortopathy shares similarities with Marfan aortopathy: BAV aortic tissues have lower fibrillin content and greater TGF-β1 levels which is due to the disease (21,25,26).…”

“…These are all interspersed with SMCs and form lamellar plates within the vessels (20). Although the number of lamellae seems to remain constant after birth, there are more of them in larger vessels that are exposed to greater wall tension (20,21).…”

“…Histologic diversity is also seen throughout different segments of the ascending aorta within the same patient for those with aortic aneurysm. The adventitia and intima are both thickened (21,23). The greater curvature of the aorta is more commonly dilated in patients with BAV, a change often attributed to greater shear stress from asymmetric flow across the valve.…”

Plasma Metabolomic Profiling Associates Bicuspid Aortic Valve Disease and Ascending Aortic Dilation with a Decrease in Antioxidant Capacity

“…Focusing on hemodynamic causes, the bicuspid morphology of the aortic valve causes an abnormal biochemical environment, a consequence mainly of the non-physiological hemodynamic impact on the ascending aorta. This morphology-associated helical flow alteration that propagates flow eccentricity leads to increased wall shear stress on the endothelium and progressive dilation of the ascending aorta [18,19]. Although BAV disease is asymptomatic initially, the lack of an early diagnosis can lead to identifying the case in advanced stages or after an event.…”