Physiol. Genomics 34: 185-192, 2008.
First published May 27, 2008; doi:10.1152/physiolgenomics.90201.2008
1094-8341/08 $8.00
Received 22 March 2008;
accepted in final form 20 May 2008.
Physiological Genomics 34:185-192 (2008)
1094-8341/08 $8.00 © 2008 American Physiological Society
Serial analysis of the vascular endothelial transcriptome under static and shear stress conditions
Tian Jiao Chu and
David G. Peters
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, and Centre for Fetal Medicine, Magee-Womens Research Institute, Pittsburgh, Pennsylvania
We have utilized serial analysis of gene expression (SAGE) to analyze the response of human coronary artery endothelial cells (HCAECs) to laminar shear stress (LSS). Primary cultures of HCAECs were exposed to 15 dyn/cm2 LSS for 24 h in a parallel plate flow chamber and compared with identical same passage cells cultured under static conditions. The expression levels of a number of functional categories of genes were reduced by shear stress including those encoding proteins involved in cell proliferation (CDC10, CDC20, CDC23, CCND1, CCNB1), angiogenesis (ANGPTL4, CTGF, CYR61, ENG, EPAS1, EGFR, LGALS3, PGK1, and SPARC), extracellular matrix and cell-matrix adhesion (EFEMP1, LOXL2, P4HB, FBN1, FN1, ITGA5, ITGAE, ITGAV, ILK, LAMR1) and ATP synthesis (ATP5G3, ATP5J2, ATP5L, ATP5D). We also observed an increase in the LSS-responsive expression of genes encoding stress response proteins, including HMOX1, which is significant since HMOX1 may have anti-inflammatory and vasodilatory vascular effects. The autosomal dominant polycystic kidney disease (ADPKD) genes PKD1 and PKD2 were also elevated by LSS. ADPKD is associated with vascular malfunction, including the impairment of vasoreactive processes. To our knowledge, this is the first SAGE-based analysis of the shear stress-responsive endothelial cell transcriptome. These immortal data provide a resource for further analyses of the molecular mechanisms underlying the biological response to LSS and contribute to the expanding collection of publicly available SAGE data.
gene expression; atherosclerosis; endothelial cell; serial analysis of gene expression
Copyright © 2008 by the American Physiological Society.