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Oxidative Stress in Cardiac Valve Development

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Studies on Atherosclerosis

Abstract

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.

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Abbreviations

aVIC:

Activated valve interstitial cell

BMP:

Bone morphogenetic protein

ECM:

Extracellular matrix

EMT:

Endothelial-to-mesenchymal transformation

eNOS:

Endothelial nitric oxide signaling

eNOS:

Endothelial nitric oxide synthase

ERK:

Extracellular-signal-regulated kinase

MAPK:

Mitogen-activated protein kinase

MMP:

Matrix metalloproteinases

NFATc1:

Nuclear factor of activated T-cells (c1)

ROS:

Reactive oxygen species

SMA:

α-Smooth muscle actin

Tgfβ:

Transforming Growth Factor β

VEC:

Valve endothelial cell

VEGF:

Vascular endothelial growth factor

VIC:

Valve interstitial cell

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Authors and Affiliations

  1. Molecular and Cellular Pharmacology Graduate Program, Leonard M. Miller School of Medicine, P.O. Box 016189 (R-189), Miami, FL, USA

    Danielle Huk

  2. Center for Cardiovascular Research at Nationwide Children’s Research Institute and The Heart Center at Nationwide Children’s Hospital, 575 Children’s Crossroads, Research Building III, WB4239, Columbus, OH, 43215, USA

    Danielle Huk & Joy Lincoln

  3. Department of Pediatrics, The Ohio State University, Columbus, OH, USA

    Joy Lincoln

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  2. Joy Lincoln
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Correspondence to Joy Lincoln .

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Editors and Affiliations

  1. Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA

    Martin Rodriguez-Porcel

  2. University of Mississippi, Jackson, Mississippi, USA

    Alejandro R. Chade

  3. Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA

    Jordan D. Miller

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Huk, D., Lincoln, J. (2017). Oxidative Stress in Cardiac Valve Development. In: Rodriguez-Porcel, M., Chade, A., Miller, J. (eds) Studies on Atherosclerosis. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Boston, MA. https://doi.org/10.1007/978-1-4899-7693-2_1

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