Abstract

We analyzed the effect of change in frequency of uniform or disturbed pulsatile flow on human umbilical vein endothelial cells (HUVECs) in the presence or absence of thrombin (Th). We found that tissue factor (TF) RNA expression in HUVECs exposed to 60 cycles per minute (cpm) of disturbed and uniform flow was significantly higher than that induced by 30 cpm. HUVECs exposed to disturbed flow have significantly higher TF RNA expression than HUVECs exposed to uniform flow at either frequency. We conclude that frequency of pulsatile flow is a critical independent factor in TF RNA expression in HUVECs.

Highlights

  • Numerous studies demonstrate that atherosclerotic lesion development occurs at the site of the blood vessel that is subjected to disturbed flow [1,2,3], such as the lesser curve of the aortic arch or at bifurcations

  • Our laboratory has investigated the role of mechanical forces on endothelial cells (ECs) [7,8,9,10], and we have previously reported a significant increase in tissue factor (TF) expression of ECs exposed to disturbed flow [7,11,12]

  • The shear stresses were 1) 60 cycle per minute of PFF, i.e. a forward square wave impulse for 0.5 sec alternating with no flow for 0.5 sec, 2) 30 cpm of PFF, i.e. a forward square wave impulse for 0.25 sec alternating with no flow for 0.25 sec, 3) 60 cpm of TFF, i.e. a forward square wave impulse for 0.5 sec alternating with a backward square wave impulse for 0.5 sec and 4) 30 cpm of TFF, i.e. a forward square wave impulse for 0.25 sec alternating with a backward square wave impulse for 0.25 sec

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Summary

Introduction

Numerous studies demonstrate that atherosclerotic lesion development occurs at the site of the blood vessel that is subjected to disturbed flow [1,2,3], such as the lesser curve of the aortic arch or at bifurcations. These observations have led researchers to hypothesize that different types of blood flow have different effects on the function of endothelial cells (ECs) that line the blood vessels and are directly exposed to hemodynamic forces. The major mechanical force is fluid shear stress, the frictional force on ECs generated by blood flow. TF has been demonstrated to contribute to the hyperthrombotic state of human atherosclerotic vessels [6], and an excessive expression of TF results in an acute thrombotic event, leading to complications of atherosclerosis

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