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Valve Endothelial Cell Exposure to High Levels of Flow Oscillations Exacerbates Valve Interstitial Cell Calcification

The aortic valve facilitates unidirectional blood flow to the systemic circulation between the left cardiac ventricle and the aorta. The valve’s biomechanical function relies on thin leaflets to adequately open and close over the cardiac cycle. A monolayer of valve endothelial cells (VECs) resides o...

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Autores principales: Hsu, Chia-Pei Denise, Tchir, Alexandra, Mirza, Asad, Chaparro, Daniel, Herrera, Raul E., Hutcheson, Joshua D., Ramaswamy, Sharan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9405348/
https://www.ncbi.nlm.nih.gov/pubmed/36004918
http://dx.doi.org/10.3390/bioengineering9080393
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author Hsu, Chia-Pei Denise
Tchir, Alexandra
Mirza, Asad
Chaparro, Daniel
Herrera, Raul E.
Hutcheson, Joshua D.
Ramaswamy, Sharan
author_facet Hsu, Chia-Pei Denise
Tchir, Alexandra
Mirza, Asad
Chaparro, Daniel
Herrera, Raul E.
Hutcheson, Joshua D.
Ramaswamy, Sharan
author_sort Hsu, Chia-Pei Denise
collection PubMed
description The aortic valve facilitates unidirectional blood flow to the systemic circulation between the left cardiac ventricle and the aorta. The valve’s biomechanical function relies on thin leaflets to adequately open and close over the cardiac cycle. A monolayer of valve endothelial cells (VECs) resides on the outer surface of the aortic valve leaflet. Deeper within the leaflet are sublayers of valve interstitial cells (VICs). Valve tissue remodeling involves paracrine signaling between VECs and VICs. Aortic valve calcification can result from abnormal paracrine communication between these two cell types. VECs are known to respond to hemodynamic stimuli, and, specifically, flow abnormalities can induce VEC dysfunction. This dysfunction can subsequently change the phenotype of VICs, leading to aortic valve calcification. However, the relation between VEC-exposed flow oscillations under pulsatile flow to the progression of aortic valve calcification by VICs remains unknown. In this study, we quantified the level of flow oscillations that VECs were exposed to under dynamic culture and then immersed VICs in VEC-conditioned media. We found that VIC-induced calcification was augmented under maximum flow oscillations, wherein the flow was fully forward for half the cardiac cycle period and fully reversed for the other half. We were able to computationally correlate this finding to specific regions of the aortic valve that experience relatively high flow oscillations and that have been shown to be associated with severe calcified deposits. These findings establish a basis for future investigations on engineering calcified human valve tissues and its potential for therapeutic discovery of aortic valve calcification.
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spelling pubmed-94053482022-08-26 Valve Endothelial Cell Exposure to High Levels of Flow Oscillations Exacerbates Valve Interstitial Cell Calcification Hsu, Chia-Pei Denise Tchir, Alexandra Mirza, Asad Chaparro, Daniel Herrera, Raul E. Hutcheson, Joshua D. Ramaswamy, Sharan Bioengineering (Basel) Article The aortic valve facilitates unidirectional blood flow to the systemic circulation between the left cardiac ventricle and the aorta. The valve’s biomechanical function relies on thin leaflets to adequately open and close over the cardiac cycle. A monolayer of valve endothelial cells (VECs) resides on the outer surface of the aortic valve leaflet. Deeper within the leaflet are sublayers of valve interstitial cells (VICs). Valve tissue remodeling involves paracrine signaling between VECs and VICs. Aortic valve calcification can result from abnormal paracrine communication between these two cell types. VECs are known to respond to hemodynamic stimuli, and, specifically, flow abnormalities can induce VEC dysfunction. This dysfunction can subsequently change the phenotype of VICs, leading to aortic valve calcification. However, the relation between VEC-exposed flow oscillations under pulsatile flow to the progression of aortic valve calcification by VICs remains unknown. In this study, we quantified the level of flow oscillations that VECs were exposed to under dynamic culture and then immersed VICs in VEC-conditioned media. We found that VIC-induced calcification was augmented under maximum flow oscillations, wherein the flow was fully forward for half the cardiac cycle period and fully reversed for the other half. We were able to computationally correlate this finding to specific regions of the aortic valve that experience relatively high flow oscillations and that have been shown to be associated with severe calcified deposits. These findings establish a basis for future investigations on engineering calcified human valve tissues and its potential for therapeutic discovery of aortic valve calcification. MDPI 2022-08-16 /pmc/articles/PMC9405348/ /pubmed/36004918 http://dx.doi.org/10.3390/bioengineering9080393 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hsu, Chia-Pei Denise
Tchir, Alexandra
Mirza, Asad
Chaparro, Daniel
Herrera, Raul E.
Hutcheson, Joshua D.
Ramaswamy, Sharan
Valve Endothelial Cell Exposure to High Levels of Flow Oscillations Exacerbates Valve Interstitial Cell Calcification
title Valve Endothelial Cell Exposure to High Levels of Flow Oscillations Exacerbates Valve Interstitial Cell Calcification
title_full Valve Endothelial Cell Exposure to High Levels of Flow Oscillations Exacerbates Valve Interstitial Cell Calcification
title_fullStr Valve Endothelial Cell Exposure to High Levels of Flow Oscillations Exacerbates Valve Interstitial Cell Calcification
title_full_unstemmed Valve Endothelial Cell Exposure to High Levels of Flow Oscillations Exacerbates Valve Interstitial Cell Calcification
title_short Valve Endothelial Cell Exposure to High Levels of Flow Oscillations Exacerbates Valve Interstitial Cell Calcification
title_sort valve endothelial cell exposure to high levels of flow oscillations exacerbates valve interstitial cell calcification
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9405348/
https://www.ncbi.nlm.nih.gov/pubmed/36004918
http://dx.doi.org/10.3390/bioengineering9080393
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