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PRE-CLINICAL RESEARCH

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

Ismail El-Hamamsy, MD^_*, Kartik Balachandran, MS, Magdi H. Yacoub, FRS^_*,_*, Louis M. Stevens, MD, SM, Padmini Sarathchandra, PhD^_*, Patricia M. Taylor, PhD^_*, Ajit P. Yoganathan, PhD and Adrian H. Chester, PhD^_*

^_* Tissue Engineering Department, Harefield Heart Science Centre, National Heart and Lung Institute, Imperial College London, Harefield, United Kingdom
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia
School of Public Health, Harvard University, Boston, Massachusetts

Manuscript received September 3, 2008; revised manuscript received November 5, 2008, accepted November 6, 2008.

^_* Reprint requests and correspondence: Sir Magdi H. Yacoub, Harefield Heart Science Centre, Hill End Road, Harefield, Middlesex UB9 6JH, United Kingdom (Email: m.yacoub{at}imperial.ac.uk).

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.

Key Words: aortic valve • mechanical properties • endothelium • nitric oxide

Abbreviations and Acronyms   CyB = cytochalasin B   ET = endothelin   5-HT = 5-hydroxytryptamine   L-NAME = N-nitro-L-arginine-methyl-ester   NO = nitric oxide   SMA = smooth muscle alpha-actin

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