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Left Ventricle Cardiac Fibroblast Transcriptome Regulation by Aldosterone In Vivo
Author(s) -
Ball Jana,
Syed Maryam,
Romero Damian
Publication year - 2015
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.29.1_supplement.665.12
Subject(s) - transcriptome , biology , in vivo , cardiac fibrosis , fibrosis , gene expression , microbiology and biotechnology , medicine , gene , genetics
Excess aldosterone (ALDO) causes cardiac hypertrophy, inflammation and fibrosis that lead to cardiac dysfunction. We previously reported that ALDO/SALT time‐dependently modulates left ventricle (LV) transcriptome in vivo . However, the cardiac fibroblast (CF)‐specific transcriptome regulation by ALDO in vivo is unknown. Even the role of CFs in ALDO‐mediated cardiac injury has been questioned. Uninephrectomized male Sprague Dawley rats were treated with ALDO (0.15 µg/h) and SALT (1.0% NaCl + 0.3% KCl) or vehicle for 2 weeks (N=6/group). LV CFs were isolated and CD90+ cells sorted by flow cytometry. Whole genome transcriptome was probed with Rat Gene 2.0‐ST Affymetrix arrays. Gene expression was analyzed with SAM software and DAVID and Ingenuity software used for bioinformatics analysis. Isolated cells were positive for CF markers (Thy1, vimentin, Fsp1, Ddr2) while negative for cardiomyocyte (Tnnt2) and endothelial cell (CD31) markers. ALDO/SALT regulated (FC蠅1.5‐fold, FDR=10) 950 genes (740 UP and 210 DOWN). Upregulated genes were significantly enriched in the following gene ontology categories: immune response (68 genes), cell cycle (52), chemotaxis (22) and migration (32). Surprisingly, downregulated genes were significantly enriched in the gene ontology category “detection of chemical stimulus involved in sensory perception of smell” with 49 distinct GPCR olfactory receptors downregulated. Our results show that the LV CFs are an ALDO target in vivo despite recent controversy in the field. Furthermore, we identified not only novel genes but completely new gene families that are targeted by ALDO in CFs in vivo , suggesting novel therapeutic approaches for patients with excess ALDO‐mediated cardiac injury.