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A Model to Study Endothelial-Mediated Valve Disease and Repair Potential of VECs
Emily Nordquist, Michael Mcdermott, Joy Lincoln.
Nationwide Children's Hospital, Columbus, OH, USA.

OBJECTIVE:
As the heart valves open and close 100,000 times each day, the overlying valve endothelial cells (VECs) are exposed to significant biomechanical stress and circulating risk factors. It is hypothesized that damage to this protective VEC layer can be an initiating factor for the development of valve disease. However, model systems to study this process are limited. Therefore, our objective is to utilize an in vivo murine wire injury model to gain insights into the mechanisms of endothelial-mediated valve disease and explore VEC plasticity and repair potential as possible therapeutic targets.
METHODS:
Building on a previously published protocol (Honda et al., 2014), we have adapted a murine model of VEC injury which involves moving a guidewire across the aortic valve under echocardiographic guidance in order to cause physical damage to the VEC layer. With a combination of functional and histological studies, we have observed the valve response to this endothelial injury.
RESULTS:
In preliminary studies, Evanís blue dye and histological analysis confirms that valve wire injury results in disruption of the VEC layer when compared to sham controls. Although procedure survival was over 90%, approximately 80% of wire injury mice develop aortic regurgitation within 4 weeks. This regurgitation is associated with thickened leaflets, disorganized matrix, and activation of VICs. Additionally, proliferation of the VEC layer was observed, indicating the potential of VECs to engage in valve repair processes.
CONCLUSIONS:
We have developed an in vivo model of VEC injury and have demonstrated the adverse effects of endothelial damage on structure-function relationships of the leaflet. In the future, we will utilize this model to define the mechanisms of VEC-mediated valve disease and explore the repair capacity of VECs.


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