A Notch more: Molecular players in bicuspid aortic valve disease. (September 2019)

• Record Type: Journal Article
• Authors: Lee, Angela; Wei, Sunny; Schwertani, Adel
• Is Part Of: Journal of molecular and cellular cardiology. Volume 134(2019)
• Page Start: 62
• Page End: 68
• Publication Date: 2019-09
• Subjects: Bicuspid aortic valve -- Calcification -- Cellular mediator -- Lipoprotein A -- Notch -- Wnt; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2019.05.018
• Languages: English
• ISSNs: 0022-2828

Abstract

Abstract: The prevalence of calcification of human aortic valve in populations 65 years old and greater is estimated to be 2–3%. Bicuspid aortic valve disease (BAVD) is a common etiology of aortic stenosis in populations aged 60–75 years of age; 30–50% of operated cases of aortic stenosis were due to calcified BAVD. Dysregulation of the Notch and the canonical Wnt pathway has been well documented to be associated with calcification of the aortic valve. However, recent studies have increased this scope to include the non-canonical pathway where Wnt5a, Wnt5b and Wnt 11 levels were significantly greater in calcified human aortic valves than normal valves, and with Wnt5b specifically being implicated in BAVD pathogenesis. More recently, Lipoprotein(a) [Lp(a)] has been implicated as a key player in the pathogenesis of calcific aortic valve disease. It has been shown that the osteogenic effect of Lp(a) is mediated through the oxidized phospholipid pathway as well as oxidized phospholipid independent pathways involving mitogen-activated protein kinases (MAPK), glycogen synthase kinase (GSK) and Wnt. Moving forward, further work needs to be conducted in order to elucidate the crosstalk between the different signaling cascades, specifically with regard to BAVD. Highlights: Bicuspid aortic valve disease is associated with calcific aortic valve disease. Dysregulation of Notch promotes calcification of the aortic valve. Wnt5b is a possible mediator in bicuspid aortic valve pathogenesis. Lipoprotein(a) drives valve calcification; its role in bicuspid disease is unclear.