Vascular injury post stent implantation: different gene expression modulation in human umbilical vein endothelial cells (HUVECs) model

PLoS One. 2014 Feb 26;9(2):e90213. doi: 10.1371/journal.pone.0090213. eCollection 2014.

Abstract

To explore whether stent procedure may influence transcriptional response of endothelium, we applied different physical (flow changes) and/or mechanical (stent application) stimuli to human endothelial cells in a laminar flow bioreactor (LFB) system. Gene expression analysis was then evaluated in each experimental condition. Human umbilical vein endothelial cells (HUVECs) were submitted to low and physiological (1 and 10 dyne/cm(2)) shear stress in absence (AS) or presence (PS) of stent positioning in a LFB system for 24 h. Different expressed genes, coming from Affymetrix results, were identified based on one-way ANOVA analysis with p values <0.01 and a fold changed >3 in modulus. Low shear stress was compared with physiological one in AS and PS conditions. Two major groups include 32 probes commonly expressed in both 1AS versus 10AS and 1PS versus 10PS comparison, and 115 probes consisting of 83 in addition to the previous 32, expressed only in 1PS versus 10PS comparison. Genes related to cytoskeleton, extracellular matrix, and cholesterol transport/metabolism are differently regulated in 1PS versus 10PS condition. Inflammatory and apoptotic mediators seems to be, instead, closely modulated by changes in flow (1 versus 10), independently of stent application. Low shear stress together with stent procedure are the experimental conditions that mainly modulate the highest number of genes in our human endothelial model. Those genes belong to pathways specifically involved in the endothelial dysfunction.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Stents / adverse effects*
  • Stress, Mechanical
  • Transcription, Genetic
  • Transcriptome*
  • Vascular System Injuries / etiology*
  • Vascular System Injuries / genetics*
  • Vascular System Injuries / pathology

Grants and funding

This study was supported by grant from FP7-ICT-2007 ARTreat project (grant agreement 224297) and CNR National Project ME.01 Malattie Cardiopolmonari Dept. of Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.