Abstract

Dramatic changes of pressure in the local circulation flow field would lead to alterations in biorheological characteristics of Endothelial cells(ECs), and futher resulted in the apoptosis induced by loss of anchorage, a form of cell death known as anoikis. In this study, we set levels of pressure(negative and positive pres- sure) loaded ECs groups and non-activated cultured ECs ,single shear stress loaded ECs as control group to demonstrate the effects of pressure shift on cell morphogenesis and adhesion. Furthermore, we in- vestigate the effects of pressure shift on ECs proli- feration and apoptosis to elucidate the influences of pressure shift on vitality of ECs. We present these data here to suggest that the negative pressure might be another important factor beyond velocity and shear stress in biomechanical impairment on ECs, then to trigger the apoptosis with the extracellular matrix (ECM) detachment (anoikis). As the negative pressure is thought to play a role in the anoikis process, these results have implications for both the path- ogenesis and therapeutics investigations of stenostic vessel dis- eases and the future vascular tissue engineering.

Highlights

  • The role of the Extracellular matrix (ECM) goes beyond providing the physical scaffold on which the Endothelial cells (ECs) adhere, it provides ECs with information for proliferation, migration, differentiation and survival through the structural and functional links

  • Dramatic changes of pressure in the local circulation flow field would lead to alterations in biorheological characteristics of Endothelial cells(ECs), and futher resulted in the apoptosis induced by loss of anchorage, a form of cell death known as anoikis

  • We present these data here to suggest that the negative pressure might be another important factor beyond velocity and shear stress in biomechanical impairment on ECs, to trigger the apoptosis with the extracellular matrix (ECM) detachment

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Summary

Introduction

The role of the Extracellular matrix (ECM) goes beyond providing the physical scaffold on which the Endothelial cells (ECs) adhere, it provides ECs with information for proliferation, migration, differentiation and survival through the structural and functional links. Loss of these links with ECM could induce apoptosis which has been termed as anoikis, a Greek ancient word meaning “homelessness”. Previous Hydrodynamics investigations on the mechanisms of the cardiovascular wall damage, in vitro assays and in vivo models, focused on the relationship between the velocity, shear stress and the ECs, while investigations on the pressure shift (especially the negative pressure) mediated anchorage-related apoptosis (anoikis) of ECs in vitro were rarely described. Combined with our analysis of Ecs proliferation, apoptosis and the expression of apoptosis-associated protein (Caspase-3, P53, Bcl-2 and Fas), we presented correlative evidence that the negative pressure played a certain role in the genesis and progress of anoikis in the flow field in vitro

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