Enlightening the Association between Bicuspid Aortic Valve and Aortopathy

Figures

• 

  Figure 1. Mechanisms involved in cystic medial necrosis, eventually leading to aortopathy in BAV patients. The role of TGF-β as a mediator of ECM degradation is depicted (top left). Deficiency in fibrillin-1 leads to an excess of free and active TGF-β due to a decrease in microfibrils and a failure in matrix sequestration of the large latent complex (top left). Also, reduced microfibrils lead to decreased formation of elastic fibers. Then, TGF-β binds to its SMC membrane receptor, initiating the SMAD/TGF-β canonical pathway. Deficiency in either TGFBR1/2 or SMAD4 can also lead to aneurysm formation, along with dysregulation in the MMP/ TIMP ratio. Elastic fiber fragmentation due to MMPs takes place, as well as decrease in SMC differentiation ability and connection to elastin (bottom left). Collagen accumulation and eventually SMC loss and collagen degradation by MMPs can then occur (bottom left). All these mechanisms, in the absence of inflammation (top right), lead to aortopathy in BAV patients. (LAP = latency-associated peptide; P = phosphorylation).

• 

  Figure 2. Representation of the wall shear stress (WSS) distribution (A, posterior view of the aorta) and flow velocity (B, front view of the ascending aorta) in a healthy volunteer and a BAV patient with right coronary cusp-left coronary cusp raphe, obtained from 4D flow cardiac magnetic resonance (CMR) imaging. This is a visual indication of increased WSS at the aneurysm location and abnormal flow jet in the presence of BAV. Furthermore, the flow in the BAV patient seems to go along the anterior right curvature of the AAo and then fold inferiorly along the inner curvature, rather than accessing the transverse aortic arch, as also reported in the literature [85]. Data collected at the Clinical Research and Imaging Centre (CRiC), University of Bristol; not previously published.

• 

  Figure 3. Schematic summary of the multiscale nature of the problem of BAV aortopathy and the interplay of different dimensions. The blue arrows indicate the known or possible interplay between genetics, hemodynamic alterations, and other factors underlying BAV aortopathy. These represent stimulating areas of current and future research.