Side-specific mechanical properties of valve endothelial cells

Michele Miragoli, Magdi H. Yacoub, Ismail El-Hamamsy, Jose L. Sanchez-Alonso, Alexey Moshkov, Napachanok Mongkoldhumrongkul, Muralindar Padala, Saravanan Paramagurunathan, Padmini Sarathchandra, Yuri E. Korchev, Julia Gorelik, Adrian H. Chester

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume307
Issue number1
DOIs
Publication statusPublished - Jul 1 2014

Keywords

  • Aortic valve
  • Biomechanics
  • Endothelin
  • Living cell imaging
  • Nitric oxide

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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