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

ObjectivesThe aim of this study was to evaluate the role of valve endothelium in regulating the mechanical properties of aortic valve cusps.BackgroundMechanical properties of valve cusps are key to their function and durability; however, little is known about the regulation of valve biomechanics.MethodsMechanical 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.ResultsUnder 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.ConclusionsThese 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.