Endothelium-Dependent Regulation of the Mechanical Properties of Aortic Valve Cusps

Objectives: The aim of this study was to evaluate the role of valve endothelium in regulating the mechanical properties of aortic valve cusps. Background: Mechanical properties of valve cusps are key to their function and durability; however, little is known about the regulation of valve biomechanics. Methods: Mechanical properties of porcine aortic valve leaflets were evaluated in response to serotonin (5-hydroxytryptamine [5-HT]), with and without N-nitro-l-arginine-methyl-ester (L-NAME) or endothelial denudation, and endothelin (ET)-1, with and without cytochalasin-B. Results: Under physiological loading conditions, 5-HT induced a decrease in the areal stiffness of the cusp (-25.0 ± 4.0%; p < 0.01 vs. control), which was reversed by L-NAME or endothelial denudation (+17.5 ± 5.3%, p = 0.07, and +14.7 ± 1.8%, p < 0.05 vs. control, respectively). ET-1 caused an increase in stiffness (+34.4 ± 13.8%; p < 0.05 vs. control), but not in the presence of cytochalasin-B (p = 0.29 vs. control). Changes in cusp stiffness were accompanied by aortic cusp relaxations to 5-HT (-0.29% ± 0.1% change in load per 10-fold increase in 5-HT concentration; p = 0.03), which were reversed by endothelial denudation (+0.29 ± 0.06% change in load per 10-fold increase in 5-HT concentration; p = 0.02) and by L-NAME (p < 0.05). Valve cusps contracted in response to ET-1 (+0.29 ± 0.08% change in load per 10-fold increase in ET-1 concentration; p = 0.02), which was inhibited by cytochalasin-B. Conclusions: These data highlight the role of the endothelium in regulating the mechanical properties of aortic valve cusps and underline the importance of valve cellular integrity for optimal valve function.