Differential responses to pulsatile and steady shear stress by endothelial cells

Abstract

Pulsations in arterial blood flow expose the endothelium to diverse mechanical forces. We hypothesize that the temporal variations in pulsatile, arterial shear stress differentially regulate endothelial gene expression compared to steady, arterial shear stress. An in vitro model was designed to replicate the shear stress level and waveform of the common carotid artery. Total RNA from human umbilical vein endothelial cells (HUVEC) subjected to 24 hrs of pulsatile, arterial shear stress (average = 13 dyne/cm2, range = 6.8 to 25.0 dyne/cm2; 1 Hz); steady, arterial shear stress (13 dyne/cm2); or static condition was collected for microarray analysis. Normalized intensities were filtered for 1.5 fold (shear vs. static) and subjected to ANOVA with Benjamini and Hochberg multiple testing correction at a false discovery rate of 5%. Over 200 genes were differentially regulated by pulsatile shear stress compared to steady shear stress, but hierarchal cluster analysis indicated HUVEC respond similarly to both types of shear stress (Pearson correlation coefficient = 0.85). Data mining of the differentially expressed genes with Ingenuity Pathways Analysis and Expression Analysis Systematic Explorer (EASE) identified several prominent biological themes including lipid metabolism, pantothenate and CoA biosynthesis, nitric oxide signaling, and metal ion processes. Taken together, these results suggest that subtle differences in endothelial responses to time variations in shear stress may involve nitric oxide. [HL18672]