Transcriptomics

Dataset Information

7

Transcription profiling of mouse vascular tissue from estrogen receptor alpha knockout (ERaKO) and estrogen receptor beta knockout (ERbKO) mice and vs. wild type control, all ovarioectomized treated with 17beta-estradiol pellets vs. placebo


ABSTRACT: Estrogen plays an important role in the regulation of vascular tone and in the pathophysiology of cardiovascular disease. Physiological effects of estrogen are mediated through estrogen receptors alpha (ERalpha) and beta (ERbeta), which are both expressed in vascular smooth muscle and endothelial cells. However, the molecular pathways mediating estrogen effects in blood vessels are not well defined. We have performed gene expression profiling in the mouse aorta to identify comprehensive gene sets the expression of which is regulated by long-term (1 wk) estrogen treatment. The ER subtype dependence of the alterations in gene expression was characterized by parallel gene expression profiling experiments in ERalpha-deficient [ERalpha knockout (ERalphaKO)] and ERbeta-deficient (ERbetaKO) mice. Importantly, these data revealed that ERalpha- and ERbeta-dependent pathways regulate distinct and largely nonoverlapping sets of genes. Whereas ERalpha is essential for most of the estrogen-mediated increase in gene expression in wild-type aortas, ERbeta mediates the large majority of estrogen-mediated decreases in gene expression. Biological functions of the estrogen-regulated genes include extracellular matrix synthesis, in addition to electron transport in the mitochondrion and reactive oxygen species pathways. Of note, the estrogen/ERbeta pathway mediates down-regulation of mRNAs for nuclear-encoded subunits in each of the major complexes of the mitochondrial respiratory chain. Several estrogen-regulated genes also encode transcription factors. Overall, these findings provide a foundation for understanding the molecular basis for estrogen effects on vasculature gene expression. Experiment Overall Design: Six estrogen receptor alpha knockout (ERaKO) and six estrogen receptor beta knockout (ERbKO) mice and ten of their wild-type littermates (all female, 2.5-4.5 months of age) were ovarioectomized. Half the mice from each genotype were implanted with 17beta-estradiol pellets, the other half with placebo pellets. After 7-8 days of estrogen/placebo treatment, aortas were harvested, total RNAs were purified for Affymetrix GeneChip microarray analysis, without pooling. This experiment consists of 6 groups with 3 (ERaKO and ERbKO) or 5 (WT) biological replicates per group, for a total of 22 samples.

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Mus musculus  

SUBMITTER: Ulla Hansen  

PROVIDER: E-GEOD-9371 | ArrayExpress | 2008-06-17

SECONDARY ACCESSION(S): GSE9371PRJNA103077

REPOSITORIES: GEO, ArrayExpress

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Publications

Estrogen receptors alpha and beta mediate distinct pathways of vascular gene expression, including genes involved in mitochondrial electron transport and generation of reactive oxygen species.

O'Lone Raegan R   Knorr Katrin K   Jaffe Iris Z IZ   Schaffer Michael E ME   Martini Paolo G V PG   Karas Richard H RH   Bienkowska Jadwiga J   Mendelsohn Michael E ME   Hansen Ulla U  

Molecular endocrinology (Baltimore, Md.) 20070320 6


Estrogen plays an important role in the regulation of vascular tone and in the pathophysiology of cardiovascular disease. Physiological effects of estrogen are mediated through estrogen receptors alpha (ERalpha) and beta (ERbeta), which are both expressed in vascular smooth muscle and endothelial cells. However, the molecular pathways mediating estrogen effects in blood vessels are not well defined. We have performed gene expression profiling in the mouse aorta to identify comprehensive gene set  ...[more]

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