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Role of 17[beta]‐estradiol and estrogen receptor [beta] in the genomic response to hypertrophy
Author(s) -
Kararigas Georgios,
Fliegner Daniela,
RegitzZagrosek Vera
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.791.2
Subject(s) - estrogen receptor , estrogen receptor alpha , muscle hypertrophy , medicine , estrogen receptor beta , endocrinology , microarray analysis techniques , knockout mouse , receptor , microarray , estrogen , pressure overload , signal transduction , biology , gene , gene expression , chemistry , microbiology and biotechnology , genetics , cardiac hypertrophy , cancer , breast cancer
We and others have clearly indicated an important role for 17β‐estradiol (E2) and estrogen receptor β (ERβ) in attenuating pressure overload (PO)‐induced left ventricular hypertrophy (LVH). However, the underlying molecular mechanisms are poorly understood. Here, we investigated the role of E2/ERβ signaling in PO‐induced LVH at a genome‐wide level. Female wild‐type (WT) and ERβ knockout (ERβ −/− ) cycling C57Bl6 mice were subjected to transverse aortic constriction (TAC) or sham surgery. At nine weeks post operation, left ventricles were harvested and RNA was hybridized to the Mouse Genome 430 2.0 Array. The microarray data were analyzed with R and Bioconductor. Assessment of single gene differential expression with a false discovery rate‐adjusted P < 0.05 identified 197 probe sets regulated in WT, 941 in ERβ −/− and 366 in both WT and ERβ −/− mice. Gene set enrichment analysis based on 1000 permutations revealed 26 pathways modulated in WT, while almost the double were modulated in ERβ −/− mice. Of these, 16 were modulated in both WT and ERβ −/− mice. Among others, the cytochrome P450 pathway was repressed in WT/TAC mice, the apoptosis pathway was induced in ERβ −/− /TAC mice, while the ECM‐receptor interaction pathway was induced in both WT and ERβ −/− /TAC mice. In conclusion, we provide evidence that the E2/ERβ axis plays an important role in the genomic response to LVH modifying the expression of several genes/pathways.