Structural and Functional Characterization of Aortic Valve Endothelial Cells in Response to Mechanical Stretch and Shear Stress: Implications for Heart Valve Tissue Engineering

Project Details

Description

Background - Valvular heart disease is a major source of cardiovascular morbidity and mortality in Canada. Current surgical options are hampered by the limited lifetime of bioprosthesis and the significant risk of bleeding and thromboembolism with mechanical prosthesis. Heart valve tissue engineering aims at producing valves from autologous tissues capable of reproducing the sophisticated functions of normal valves. This entails identifying the ideal cell population for seeding biodegradable scaffolds. Thus, it is imperative to thoroughly study the complex structure and functions of normal heart valves. Objectives - Human heart valves are composed of endothelial cells (ECs) and interstitial cells. The purpose of this project is to determine the characteristics and the function of valvular ECs on their environment in response to various stimuli. Project - Aortic valves endothelial cells (AVECs) lie on the exposed surface of cardiac valves. ECs are known to exert a regulatory role on their environment. The unique hemodynamics of aortic valves exposes these cells to a various stretching and turbulent flow patterns. We will seek to evaluate how AVECs respond to these stresses by analyzing their function and physiology. Furthermore, we will analyze the effects of AVECs on the underlying interstitial cells which are responsible for extracellular matrix production and valvular remodeling. Implications - The best way to engineer a human heart valve is by thoroughly understanding its function. We believe these results will move us significantly closer to that goal. These results will establish a blueprint for AVECs, helping identify suitable cell populations to use in the future (mesenchymal stem cells, human umbilical vein ECs). In addition, it will help in the understanding of certain disease processes, like calcified aortic stenosis, by clarifying the response of ECs to hemodynamic stresses, which is the basis for this inflammatory process.
StatusFinished
Effective start/end date1/05/0730/04/10

Funding

  • Canadian Institutes of Health Research: $166,397.00

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