Abstract

Responses of valve endothelial cells (VECs) to shear stresses are important for the regulation of valve durability. However, the effect of flow patterns subjected to VECs on the opposite surfaces of the valves on the production of extracellular matrix (ECM) has not yet been investigated. This study aims to investigate the response of side-specific flow patterns, in terms of ECM synthesis and/or degradation in porcine aortic valves. Aortic and ventricular sides of aortic valve leaflets were exposed to oscillatory and laminar flow generated by a Cone-and-Plate machine for 48 h. The amount of collagen, GAGs and elastin was quantified and compared to samples collected from the same leaflets without exposing to flow. The results demonstrated that flow is important to maintain the amount of GAGs and elastin in the valve, as compared to the effect of static conditions. Particularly, the laminar waveform plays a crucial role on the modulation of elastin in side-independent manner. Furthermore, the ability of oscillatory flow on the aortic surface to increase the amount of collagen and GAGs cannot be replicated by exposure of an identical flow pattern on the ventricular side of the valve. Side-specific responses to the particular patterns of flow are important to the regulation of ECM components. Such understanding is imperative to the creation of tissue-engineered heart valves that must be created from the “appropriate” cells that can replicate the functions of the native VECs to regulate the different constituents of ECM.

Highlights

  • Heart valve endothelial cells (VECs) play an important role in maintaining valve integrity, in a similar way as vascular endothelial cells (ECs) do in VECs share some function with vascular ECs, studies at the genetic and molecular level reveal different transcription profiles and signalling pathways between VECs and the adjacent ECs from the aorta.[4,6] there are an increasing number of studies demonstrating the phenotypic heterogeneities of VECs on the aortic surface (AS) and ventricular surface (VS) of the aortic valve

  • It is certain that VECs and valve interstitial cells (VICs) respond to their hemodynamic environment, which can influence/determine their ability to interact with each other and to affect the remodeling of valve extracellular matrix (ECM), which is mainly composed of collagen in the fibrosa, glycosaminoglycans (GAGs) in the middle and elastin in the ventricularis

  • The collagen content of leaflets that were maintained at static control (SC) for 48 h was not significantly different to that measured in fresh tissue (FT)

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Summary

Introduction

Heart valve endothelial cells (VECs) play an important role in maintaining valve integrity, in a similar way as vascular endothelial cells (ECs) do in VECs share some function with vascular ECs, studies at the genetic and molecular level reveal different transcription profiles and signalling pathways between VECs and the adjacent ECs from the aorta.[4,6] there are an increasing number of studies demonstrating the phenotypic heterogeneities of VECs on the aortic surface (AS) and ventricular surface (VS) of the aortic valve These include a differential gene transcription profile,[22] differential production of NOS III and Cx43 proteins and the differential expression of miRNA-70 in a flow-pattern independent manner.[7,8,21]. The leaflet kept in a static mechanical environment had an

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