Key result
Serotonin reduces aortic valve cusp areal stiffness by ~25% through an endothelium-dependent mechanism.
Why the study?
Little is known about the regulation of mechanical properties of aortic valve cusps by the valve endothelium.
The valve endothelium actively regulates the mechanical properties of aortic valve cusps through mediators such as serotonin and endothelin-1.
No immediate clinical implications; leaves open whether endothelial regulation of valve stiffness translates to human disease.
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.
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El-Hamamsy et al. (2009) studied Aortic valve biomechanics. Serotonin (5-HT) and endothelin (ET)-1 vs. Control (with or without L-NAME, endothelial denudation, or cytochalasin-B) was evaluated on Areal stiffness of the cusp (p=<0.01). Serotonin induced a 25.0% decrease in areal stiffness of porcine aortic valve cusps (P<0.01), which was reversed by endothelial denudation, demonstrating the endothelium regulates valve biomechanics.
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