Developmental Mechanisms of Aortic Valve Malformation and Disease

• Published in: Annual review of physiology Vol. 79; no. 1; pp. 21 - 41
• Main Authors: Wu, Bingruo, Wang, Yidong, Xiao, Feng, Butcher, Jonathan T, Yutzey, Katherine E, Zhou, Bin
• Format: Journal Article
• Language: English
• Published: United States Annual Reviews 10.02.2017; Annual Reviews, Inc
• Subjects: animal model; Animals; Aortic Valve - pathology; bicuspid aortic valve; Cardiovascular disease; cell signaling; Endothelial Cells - pathology; heart valve development; Heart Valve Diseases - genetics; Heart Valve Diseases - pathology; Humans; Medical treatment; Mutation; Pathogenesis; Rodents; Signal Transduction - genetics; Stem cells; valve endocardial cell; valve interstitial cell; valve endocardial cell; animal model; bicuspid aortic valve; heart valve development; cell signaling; valve interstitial cell
• ISSN: 0066-4278; 1545-1585
• DOI: 10.1146/annurev-physiol-022516-034001

Normal aortic valves are composed of valve endothelial cells (VECs) and valve interstitial cells (VICs). VICs are the major cell population and have distinct embryonic origins in the endocardium and cardiac neural crest cells. Cell signaling between the VECs and VICs plays critical roles in aortic valve morphogenesis. Disruption of major cell signaling pathways results in aortic valve malformations, including bicuspid aortic valve (BAV). BAV is a common congenital heart valve disease that may lead to calcific aortic valve disease (CAVD), but there is currently no effective medical treatment for this beyond surgical replacement. Mouse and human studies have identified causative gene mutations for BAV and CAVD via disrupted VEC to VIC signaling. Future studies on the developmental signaling mechanisms underlying aortic valve malformations and the pathogenesis of CAVD using genetically modified mouse models and patient-induced pluripotent stem cells may identify new effective therapeutic targets for the disease.