Bicuspid aortic valve (BAV) is the most common type of congenital
cardiac malformation. Patients with a BAV have a predisposition for the
development of thoracic aortic aneurysm (TAA). This pathological aortic
dilation may result in aortic rupture, which is fatal in most cases. The
abnormal aortic morphology of TAAs results from a complex series of events that
alter the cellular structure and extracellular matrix (ECM) composition of the
aortic wall. Because the major degeneration is located in the media of the
aorta, most studies aim to unravel impaired smooth muscle cell (SMC) function
in BAV TAA. However, recent studies suggest that endothelial cells play a key
role in both the initiation and progression of TAAs by influencing the medial
layer. Aortic endothelial cells are activated in BAV mediated TAAs and have a
substantial influence on ECM composition and SMC phenotype, by secreting
several key growth factors and matrix modulating enzymes. In recent years there
have been significant advances in the genetic and molecular understanding of
endothelial cells in BAV associated TAAs. In this review, the involvement of
the endothelial cells in BAV TAA pathogenesis is discussed. Endothelial cell functioning
in vessel homeostasis, flow response and signalling will be highlighted to give
an overview of the importance and the under investigated potential of
endothelial cells in BAV-associated TAA.
Stem cells & developmental biolog