Side-specific mechanical properties of valve endothelial cells

Author:

Miragoli Michele12,Yacoub Magdi H.34,El-Hamamsy Ismail3,Sanchez-Alonso Jose L.1,Moshkov Alexey1,Mongkoldhumrongkul Napachanok3,Padala Muralindar5,Paramagurunathan Saravanan3,Sarathchandra Padmini3,Korchev Yuri E.6,Gorelik Julia1,Chester Adrian H.34

Affiliation:

1. Imperial College, National Heart and Lung Institute, Department of Cardiac Medicine, Imperial Centre for Translational and Experimental Medicine, Hammersmith Campus, London, United Kingdom;

2. Humanitas Clinical and Research Center, Rozzano (Milan), Italy;

3. Imperial College, National Heart and Lung Institute, Heart Science Centre, Harefield, Middlesex, United Kingdom;

4. Qatar Cardiovascular Research Centre, Qatar Foundation, Doha, Qatar;

5. Department of Surgery, Emory University School of Medicine, Atlanta, Georgia; and

6. Division of Medicine, Imperial College, Hammersmith Campus, London, United Kingdom

Abstract

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.

Publisher

American Physiological Society

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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