Author + information
- Received September 3, 2008
- Revision received November 5, 2008
- Accepted November 6, 2008
- Published online April 21, 2009.
- 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*
- ↵*Reprint requests and correspondence:
Sir Magdi H. Yacoub, Harefield Heart Science Centre, Hill End Road, Harefield, Middlesex UB9 6JH, United Kingdom
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.
Dr. El-Hamamsy is supported by a Research Fellowship Award from the Canadian Institutes of Health Research (CIHR MFE-83809) and by the Magdi Yacoub Institute. Dr. Balachandran is supported by the National Science Foundation through the ERC program at Georgia Institute of Technology under award number EEC-9731643. Drs. El-Hamamsy and Balachandran contributed equally to this work.
- Received September 3, 2008.
- Revision received November 5, 2008.
- Accepted November 6, 2008.
- American College of Cardiology Foundation