Project description:The overall objective of the study was to screen for microRNAs regulated by aldosterone and salt in rat left ventricles . Primary aldosteronism is characterized by excess aldosterone (ALDO) secretion independent of the renin-angiotensin system and accounts for ~10% of hypertensive patients. Excess ALDO, inappropriate for the salt intake status, causes cardiac hypertrophy, inflammation, fibrosis and hypertension. The molecular mechanisms that trigger the onset and progression of ALDO-mediated cardiac injury are poorly understood. MicroRNAs (miRNAs) are endogenous, small, non-coding RNAs that have been implicated in diverse cardiac pathologies, yet very little is known about their regulation and role in ALDO-mediated cardiac injury. To elucidate the regulation of miRNAs in ALDO-mediated cardiac injury, we performed a time-series analysis of left ventricle (LV) miRNA expression. Uninephrectomized male Sprague Dawley rats were treated with ALDO (0.75 µg/h) infusion and SALT (1.0% NaCl/0.3% KCl) in the drinking water for up to 8 weeks. ALDO/SALT time-dependently modulated the expression of multiple miRNAs in the LV. miR-21 was the most upregulated miRNA after 2 weeks of treatment and remained elevated until the end of the study. To elucidate the role of miR-21 in ALDO/SALT-mediated cardiac injury, miR-21 was downregulated using antagomirs in ALDO/SALT-treated rats. miR-21 downregulation exacerbated ALDO/SALT-mediated cardiac hypertrophy, fibrosis and inflammation markers gene expression, interstitial and perivascular fibrosis, OH-proline content and cardiac dysfunction. These results suggest that ALDO/SALT-mediated cardiac miR-21 upregulation may be a compensatory mechanism that mitigates ALDO/SALT-mediated cardiac deleterious effects. We speculate that miR-21 supplementation would have beneficial effects in reverting or mitigating cardiac injury and dysfunction in patients with primary aldosteronism.
Project description:We wanted to understand how a salt restriction diet could improve cardiac damage (ie cardiac hypertrophy, fibrosis, hypertension) in a rat model of metabolic syndrome. We thus performed an Agilent microarray experiment in order to identify expression variations in left ventricles of rats having a normal sodium diet (0,64%) or a low sodium diet (less than 0,01%)
Project description:In order to establish a rat embryonic stem cell transcriptome, mRNA from rESC cell line DAc8, the first male germline competent rat ESC line to be described and the first to be used to generate a knockout rat model was characterized using RNA sequencing (RNA-seq) analysis.