The Individual and Combined Effects of Shear, Tension, and Flexure on Aortic Heart Valve Endothelial Cells in Culture

Purpose: The necessity of living engineered heart valves to treat patients with severe heart disease poses a challenge to tissue engineers. To reach such goal it is crucial to fully understand the role and the activities of valvular endothelial cells (VECs) when they face different types of mechanical stimuli. This study focuses on decomposing the roles of different mechanical stimuli on heart valve endothelial surfaces and the response of VECs in terms of morphology and phenotype change. Methods: This study utilizes soft hydrogel-based scaffolds to use as a substrate for cell culture to mimic heart valve tissue leaflet. VECs were cultured as a monolayer on the gel surface and different types of mechanical stimuli were applied. Finally, the response of cells was investigated in terms of morphology and protein expression changes. Results: Single stimuli introduces actin fibers reorganization in VECs, change in cell morphology, and higher mesenchymal protein expression. On the other hand, combined stimuli application has lower impact on actin fibers reorganization and cell morphology change, with lower mesenchymal protein expression. Conclusions: When VECs face a single mechanical stimuli, they undergo transdifferentiation and transform into mesenchymal cells. However, when these cells face a combination of mechanical stimuli, the rate of transformation decreases compared to single stimuli applications. This indicates that a single stimulus induces endothelial to mesenchymal transition in VECs while the process is slower under the combination of multiple mechanical stimuli.