title: Developmental Mechanisms of Aortic Valve Malformation and Disease.
abstract: 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.
authors.affiliation: Departments of Genetics, Pediatrics, and Medicine (Cardiology), Wilf Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York 10461; email: bin.zhou@einstein.yu.edu.
authors.forename: Bingruo
authors.initials: B
authors.lastname: Wu
authors.affiliation: Departments of Genetics, Pediatrics, and Medicine (Cardiology), Wilf Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York 10461; email: bin.zhou@einstein.yu.edu.
authors.forename: Yidong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Departments of Genetics, Pediatrics, and Medicine (Cardiology), Wilf Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York 10461; email: bin.zhou@einstein.yu.edu.|Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York 14853; email: jtb47@cornell.edu.
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Butcher
authors.affiliation: Division of Molecular Cardiovascular Biology, Cincinnati Children's Medical Center, Cincinnati, Ohio 45229; email: katherine.yutzey@cchmc.org.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Yutzey
authors.affiliation: Departments of Genetics, Pediatrics, and Medicine (Cardiology), Wilf Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York 10461; email: bin.zhou@einstein.yu.edu.|Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001021:Aortic Valve / Q000473:pathology*; D042783:Endothelial Cells / Q000473:pathology; D006349:Heart Valve Diseases / Q000235:genetics / Q000473:pathology*; D006801:Humans; D015398:Signal Transduction / Q000235:genetics
keywords: animal model; bicuspid aortic valve; cell signaling; heart valve development; valve endocardial cell; valve interstitial cell