Dataset Information

MicroRNAs regulated by aldosterone/salt in rat left ventricles in vivo

ABSTRACT: 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. Overall design: Eight-week old male Sprague Dawley rats (Harlan Laboratories) were uninephrectomized and the next day randomly assigned to Control or Aldosterone/Salt (ALDO/SALT) experimental groups. ALDO (0.75 µg/h, Steraloids) was administered in PEG 300 (vehicle, Fluka) by subcutaneously implanted osmotic minipumps (Alzet 2004, Durect). SALT (1.0 % NaCl) was administered in the drinking fluid instead of tap water. ALDO-treated animals were supplemented with 0.3 % KCl in the drinking fluid to avoid hypokalemia. Animals were treated for 2, 7, 14, 28 or 56 days. Three animals per group (treatment, time) were processed individually as biological replicates. At the indicated time points, the left ventricle was excised, total RNA extracted and processed for microRNAs microarrays.

INSTRUMENT(S): miRCURY LNA microRNA Array, v.11.0 - hsa, mmu & rno [miRBase 13.0]

SUBMITTER: Damian G. Romero

PROVIDER: GSE87122 | GEO | 2017-06-15

SECONDARY ACCESSION(S): PRJNA343626

REPOSITORIES: GEO

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Publications

Role and Regulation of MicroRNAs in Aldosterone-Mediated Cardiac Injury and Dysfunction in Male Rats.

Ball Jana P JP Syed Maryam M Marañon Rodrigo O RO Hall Michael E ME Kc Roshan R Reckelhoff Jane F JF Yanes Cardozo Licy L LL Romero Damian G DG

Endocrinology 20170601 6

Primary aldosteronism is characterized by excess aldosterone (ALDO) secretion independent of the renin-angiotensin system and accounts for approximately 10% of hypertension cases. Excess ALDO that is inappropriate for 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, noncoding RNAs that have been im ...[more]

PMID: 28368454

Similar Datasets

Project description:Primary aldosteronism is characterized by excess aldosterone secretion by the adrenal gland independent of the renin-angiotensin system and accounts for ~10% of hypertensive patients. Excess aldosterone causes cardiac hypertrophy, fibrosis, inflammation, and hypertension. The molecular mechanisms that trigger the onset and progression of aldosterone-mediated cardiac injury remain incompletely understood. MicroRNAs (miRNAs) are endogenous, small, noncoding RNAs that have been implicated in multiple cardiac pathologies; however, their regulation and role in aldosterone-mediated cardiac injury and dysfunction remains mostly unknown. We previously reported that microRNA-21 (miR-21) is the most upregulated miRNA by excess aldosterone in the left ventricle in a rat experimental model of primary aldosteronism. To elucidate the role of miR-21 in aldosterone-mediated cardiac injury and dysfunction, miR-21 knockout mice and their wild-type littermates were treated with aldosterone infusion and salt in the drinking water for 2 or 8 wk. miR-21 genetic ablation exacerbated aldosterone/salt-mediated cardiac hypertrophy and cardiomyocyte cross-sectional area. Furthermore, miR-21 genetic ablation increased the cardiac expression of fibrosis and inflammation markers and fetal gene program. miR-21 genetic ablation increased aldosterone/salt-mediated cardiac dysfunction but did not affect aldosterone/salt-mediated hypertension. miR-21 target gene Sprouty 2 may be implicated in the cardiac effects of miR-21 genetic ablation. Our study shows that miR-21 genetic ablation exacerbates aldosterone/salt-mediated cardiac hypertrophy, injury, and dysfunction blood pressure independently. These results suggest that miR-21 plays a protective role in the cardiac pathology triggered by excess aldosterone. Furthermore, miR-21 supplementation may be a novel therapeutic approach to abolish or mitigate excess aldosterone-mediated cardiovascular deleterious effects in primary aldosteronism.