Journal
FRONTIERS IN CARDIOVASCULAR MEDICINE
Volume 5, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcvm.2018.00162
Keywords
aortic valve calcification; extracellular matrix; valve interstitial cell; valve endothelial cell; hemodynamics; epigenetics; signaling; development
Categories
Funding
- Research Institute at Nationwide Children's Hospital IDEA award
- [R01HL142685]
- [R01HL132801]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL142685, R01HL132801] Funding Source: NIH RePORTER
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Heart valves are dynamic, highly organized structures required for unidirectional blood flow through the heart. Over an average lifetime, the valve leaflets or cusps open and close over a billion times, however in over 5 million Americans, leaflet function fails due to biomechanical insufficiency in response to wear-and-tear or pathological stimulus. Calcific aortic valve disease (CAVD) is the most common valve pathology and leads to stiffening of the cusp and narrowing of the aortic orifice leading to stenosis and insufficiency. At the cellular level, CAVD is characterized by valve endothelial cell dysfunction and osteoblast-like differentiation of valve interstitial cells. These processes are associated with dysregulation of several molecular pathways important for valve development including Notch, Sox9, Tgf beta, Bmp, Wnt, as well as additional epigenetic regulators. In this review, we discuss the multifactorial mechanisms that contribute to CAVD pathogenesis and the potential of targeting these for the development of novel, alternative therapeutics beyond surgical intervention.
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