In vivo differences between endothelial transcriptional profiles of coronary and iliac arteries revealed by microarray analysis
- 1 October 2008
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Heart and Circulatory Physiology
- Vol. 295 (4), H1556-H1561
- https://doi.org/10.1152/ajpheart.00540.2008
Abstract
Endothelial cells (ECs) from different vascular beds display a remarkable heterogeneity in both structure and function. Phenotypic heterogeneity among arterial ECs is particularly relevant to atherosclerosis since the disease occurs predominantly in major arteries, which vary in their atherosusceptibility. To explore EC heterogeneity between typical atheroprone and atheroresistant arteries, we used DNA microarrays to compare gene expression profiles of freshly harvested porcine coronary (CECs) and iliac artery (IECs) ECs. Statistical analysis revealed 51 genes that were differentially expressed in CECs relative to IECs at a false discovery rate of 5%. Seventeen of these genes are known to be involved in atherogenesis. Consistent with coronary arteries being more atherosusceptible, almost all putative atherogenic genes were overexpressed in CECs, whereas all atheroprotective genes were downregulated, relative to IECs. A subset of the identified genes was validated by quantitative polymerase chain reaction (PCR). PCR results suggest that the differences in expression levels between CECs and IECs for the HOXA10 and HOXA9 genes were >100-fold. Gene ontology (GO) and biological pathway analysis revealed a global expression difference between CECs and IECs. Genes in twelve GO categories, including complement immune activation, immunoglobulin-mediated response, and system development, were significantly upregulated in CECs. CECs also overexpressed genes involved in several inflammatory pathways, including the classical pathway of complement activation and the IGF-1-mediated pathway. The in vivo transcriptional differences between CECs and IECs found in this study may provide new insights into the factors responsible for coronary artery atherosusceptibility.Keywords
This publication has 46 references indexed in Scilit:
- Distinct profiles of endothelial gene expression in hyperpermeable regions of the porcine aortic arch and thoracic aortaAtherosclerosis, 2007
- Artery-Related Differences in Atherosclerosis ExpressionStroke, 2007
- Common cues regulate neural and vascular patterningCurrent Opinion in Genetics & Development, 2007
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005
- A SAGE-based comparison between glomerular and aortic endothelial cellsAmerican Journal of Physiology-Renal Physiology, 2005
- Nitric oxide donors protect murine myocardium against infarction via modulation of mitochondrial permeability transitionAmerican Journal of Physiology-Heart and Circulatory Physiology, 2005
- 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
- Human Vascular Endothelium HeterogeneityStroke, 1997
- Animal models of atherosclerosisAtherosclerosis, 1990