TY - JOUR
T1 - Side-specific mechanical properties of valve endothelial cells
AU - Miragoli, Michele
AU - Yacoub, Magdi H.
AU - El-Hamamsy, Ismail
AU - Sanchez-Alonso, Jose L.
AU - Moshkov, Alexey
AU - Mongkoldhumrongkul, Napachanok
AU - Padala, Muralindar
AU - Paramagurunathan, Saravanan
AU - Sarathchandra, Padmini
AU - Korchev, Yuri E.
AU - Gorelik, Julia
AU - Chester, Adrian H.
PY - 2014/7/1
Y1 - 2014/7/1
N2 - Aortic valve endothelial cells (ECs) function in vastly different levels of shear stress. The biomechanical characteristics of cells on each side of valve have not been investigated. We assessed the morphology and mechanical properties of cultured or native valve ECs on intact porcine aortic valve cusps using a scanning ion conductance microscope (SICM). The autocrine influence of several endothelial-derived mediators on cell compliance and the expression of actin were also examined. Cells on the aortic side of the valve are characterized by a more elongated shape and were aligned along a single axis. Measurement of EC membrane compliance using the SICM showed that the cells on the aortic side of intact valves were significantly softer than those on the ventricular side. A similar pattern was seen in cultured cells. Addition of 10-6 M of the nitric oxide donor sodium nitroprusside caused a significant reduction in the compliance of ventricular ECs but had no effect on cells on the aortic side of the valve. Conversely, endothelin-1 (10-10-10-8 M) caused an increase in the compliance of aortic cells but had no effect on cells on the ventricular side of the valve. Aortic side EC compliance was also increased by 10-4 M of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester. Immunofluorescent staining of actin filaments revealed a great density of staining in ECs on the ventricular surface. The expression of actin and the relative membrane compliance of ECs on both side of the valve were not affected by ventricular and aortic patterns of flow. This study has shown side-specific differences in the biomechanics of aortic valve ECs. These differences can have important implications for valve function.
AB - Aortic valve endothelial cells (ECs) function in vastly different levels of shear stress. The biomechanical characteristics of cells on each side of valve have not been investigated. We assessed the morphology and mechanical properties of cultured or native valve ECs on intact porcine aortic valve cusps using a scanning ion conductance microscope (SICM). The autocrine influence of several endothelial-derived mediators on cell compliance and the expression of actin were also examined. Cells on the aortic side of the valve are characterized by a more elongated shape and were aligned along a single axis. Measurement of EC membrane compliance using the SICM showed that the cells on the aortic side of intact valves were significantly softer than those on the ventricular side. A similar pattern was seen in cultured cells. Addition of 10-6 M of the nitric oxide donor sodium nitroprusside caused a significant reduction in the compliance of ventricular ECs but had no effect on cells on the aortic side of the valve. Conversely, endothelin-1 (10-10-10-8 M) caused an increase in the compliance of aortic cells but had no effect on cells on the ventricular side of the valve. Aortic side EC compliance was also increased by 10-4 M of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester. Immunofluorescent staining of actin filaments revealed a great density of staining in ECs on the ventricular surface. The expression of actin and the relative membrane compliance of ECs on both side of the valve were not affected by ventricular and aortic patterns of flow. This study has shown side-specific differences in the biomechanics of aortic valve ECs. These differences can have important implications for valve function.
KW - Aortic valve
KW - Biomechanics
KW - Endothelin
KW - Living cell imaging
KW - Nitric oxide
UR - http://www.scopus.com/inward/record.url?scp=84903618053&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84903618053&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00228.2013
DO - 10.1152/ajpheart.00228.2013
M3 - Article
C2 - 24791787
AN - SCOPUS:84903618053
VL - 307
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6119
IS - 1
ER -