Environment and vascular bed origin influence differences in endothelial transcriptional profiles of coronary and iliac arteries
Open Access
- 1 September 2010
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Heart and Circulatory Physiology
- Vol. 299 (3), H837-H846
- https://doi.org/10.1152/ajpheart.00002.2010
Abstract
Atherosclerotic plaques tend to form in the major arteries at certain predictable locations. As these arteries vary in atherosusceptibility, interarterial differences in endothelial cell biology are of considerable interest. To explore the origin of differences observed between typical atheroprone and atheroresistant arteries, we used DNA microarrays to compare gene expression profiles of harvested porcine coronary (CECs) and iliac artery endothelial cells (IECs) grown in static culture out to passage 4. Fewer differences were observed between the transcriptional profiles of CECs and IECs in culture compared with in vivo, suggesting that most differences observed in vivo were due to distinct environmental cues in the two arteries. One-class significance of microarrays revealed that most in vivo interarterial differences disappeared in culture, as fold differences after passaging were not significant for 85% of genes identified as differentially expressed in vivo at 5% false discovery rate. However, the three homeobox genes, HOXA9, HOXA10, and HOXD3, remained underexpressed in coronary endothelium for all passages by at least nine-, eight-, and twofold, respectively. Continued differential expression, despite removal from the in vivo environment, suggests that primarily heritable or epigenetic mechanism(s) influences transcription of these three genes. Quantitative real-time polymerase chain reaction confirmed expression ratios for seven genes associated with atherogenesis and over- or underexpressed by threefold in CECs relative to IECs. The present study provides evidence that both local environment and vascular bed origin modulate gene expression in arterial endothelium. The transcriptional differences observed here may provide new insights into pathways responsible for coronary artery susceptibility.Keywords
This publication has 65 references indexed in Scilit:
- Oxidized Phospholipids Induce Type VIII Collagen Expression and Vascular Smooth Muscle Cell MigrationCirculation Research, 2009
- Epigenetics and atherosclerosisBiochimica et Biophysica Acta (BBA) - General Subjects, 2009
- NRP/B mutations impair Nrf2-dependent NQO1 induction in human primary brain tumorsOncogene, 2008
- In vivo differences between endothelial transcriptional profiles of coronary and iliac arteries revealed by microarray analysisAmerican Journal of Physiology-Heart and Circulatory Physiology, 2008
- Distinct profiles of endothelial gene expression in hyperpermeable regions of the porcine aortic arch and thoracic aortaAtherosclerosis, 2007
- HOXA9 Participates in the Transcriptional Activation of E-Selectin in Endothelial CellsMolecular and Cellular Biology, 2007
- DNA methylation patterns and epigenetic memoryGenes & Development, 2002
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- Significance analysis of microarrays applied to the ionizing radiation responseProceedings of the National Academy of Sciences of the United States of America, 2001
- Failure of blood-island formation and vasculogenesis in Flk-1-deficient miceNature, 1995