Side-specific mechanical properties of valve endothelial cells

被引:17
|
作者
Miragoli, Michele [1 ,2 ]
Yacoub, Magdi H. [2 ,3 ]
El-Hamamsy, Ismail [3 ]
Sanchez-Alonso, Jose L. [1 ]
Moshkov, Alexey [1 ]
Mongkoldhumrongkul, Napachanok [3 ]
Padala, Muralindar [5 ]
Paramagurunathan, Saravanan [3 ]
Sarathchandra, Padmini [3 ]
Korchev, Yuri E. [6 ]
Gorelik, Julia [1 ]
Chester, Adrian H. [3 ,4 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Dept Cardiac Med, Imperial Ctr Translat & Expt Med, London W12 0NN, Middx, England
[2] Humanitas Clin & Res Ctr, Milan, Italy
[3] Imperial Coll, Natl Heart & Lung Inst, Heart Sci Ctr, Harefield, Middx, England
[4] Qatar Fdn, Qatar Cardiovasc Res Ctr, Doha, Qatar
[5] Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA
[6] Univ London Imperial Coll Sci Technol & Med, Div Med, London W12 0NN, Middx, England
基金
加拿大健康研究院; 英国生物技术与生命科学研究理事会; 英国工程与自然科学研究理事会;
关键词
living cell imaging; aortic valve; biomechanics; nitric oxide; endothelin; ION CONDUCTANCE MICROSCOPY; NITRIC-OXIDE RELEASE; AORTIC-VALVE; VASCULAR ENDOTHELIUM; LIVING CELLS; CYTOSKELETON; ATHEROSCLEROSIS; MECHANOBIOLOGY; CALCIFICATION; HETEROGENEITY;
D O I
10.1152/ajpheart.00228.2013
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 N-G-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.
引用
收藏
页码:H15 / H24
页数:10
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