Molecular mechanisms of aortic valve pathology

Abstract

The aortic valve is a dynamic structure composed of valve interstitial cells (VICs) and valve endothelial cells (VECs), which contribute to maintain and repair the extracellular matrix (ECM). Disorders of the aortic valve, such as calcific aortic valve disease (CAVD), are characterized by the re-expression of embryonic genes involved in valvulogenesis and actively participate to the pathologic remodeling of the ECM. Studies performed in the last several years have underlined that inflammation and lipid signaling pathways are intertwined in promoting the fibrocalcific remodeling process of the aortic valve. Altered blood flow dynamics along with genetic factors are involved in disorders associated with bicuspid aortic valve (BAV), a valve with two leaflets instead of three. The control of osteogenesis in the aortic valve is complex and involves different signaling cascades such as NF-κB, NOTCH, and Wnt pathways. In this chapter, we are reviewing the basic concepts related to the biology of the aortic valve and the pathobiology behind the development of CAVD and BAV.