Oxidative Stress in Cardiac Valve Development

  • Danielle Huk
  • Joy LincolnEmail author
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)


Formation of the mature valve structures begins during embryogenesis and is initiated with the generation of endocardial cushions following endothelial-to-mesenchymal transformation. As development progresses, endocardial cushions elongate and undergo extensive remodeling of the extracellular matrix by mesenchyme-like valve interstitial cells that reside within the maturing valve primordia. This process is in part, regulated by valve endothelial cells that overlay the valve leaflets and continues until postnatal stages when formation of the stratified valve structure is complete. Many signaling pathways have been shown to regulate valvulogenesis including Transforming Growth Factor β, Vascular endothelial growth factor, Wnt, Notch, and endothelial Nitric Oxide Synthase. In other systems, components of the reactive oxygen species (ROS) serve as secondary messengers to influence activity of these signaling pathways. As this has not been explored in developing valves, this chapter will discuss the potential role of ROS in the embryo and discuss how aberrations in this process could underlie valve pathology after birth.


Heart valve Valve endothelial cell Valve interstitial cell Extracellular matrix Endocardial cushion Remodeling Transforming growth factor β Vascular endothelial growth factor Reactive oxygen species Endothelial nitric oxide synthase 



Activated valve interstitial cell


Bone morphogenetic protein


Extracellular matrix


Endothelial-to-mesenchymal transformation


Endothelial nitric oxide signaling


Endothelial nitric oxide synthase


Extracellular-signal-regulated kinase


Mitogen-activated protein kinase


Matrix metalloproteinases


Nuclear factor of activated T-cells (c1)


Reactive oxygen species


α-Smooth muscle actin


Transforming Growth Factor β


Valve endothelial cell


Vascular endothelial growth factor


Valve interstitial cell


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Molecular and Cellular Pharmacology Graduate ProgramLeonard M. Miller School of MedicineMiamiUSA
  2. 2.Center for Cardiovascular Research at Nationwide Children’s Research Institute and The Heart Center at Nationwide Children’s HospitalColumbusUSA
  3. 3.Department of PediatricsThe Ohio State UniversityColumbusUSA

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