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

Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375040 Publication Model: Print Cited Medium: Internet ISSN: 1945-7170 (Electronic) Linking ISSN: 00137227 NLM ISO Abbreviation: Endocrinology Subsets: MEDLINE

Publication: 2017- : New York : Oxford University Press
Original Publication: Los Angeles, Calif. : Association for the Study of Internal Secretions,

Aldosterone/*adverse effects ; Heart Diseases/*chemically induced ; Heart Diseases/*physiopathology ; Hyperaldosteronism/*complications ; MicroRNAs/*genetics ; MicroRNAs/*physiology; Animals ; Gene Expression Regulation ; Heart/drug effects ; Heart/physiopathology ; Heart Diseases/genetics ; Hyperaldosteronism/metabolism ; Hypertension/chemically induced ; Hypertension/physiopathology ; Male ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride/pharmacology ; Ventricular Dysfunction, Left/chemically induced ; Ventricular Dysfunction, Left/genetics ; Ventricular Dysfunction, Left/pathology ; Ventricular Dysfunction, Left/physiopathology

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 implicated in diverse cardiac abnormalities, 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 by using antagomirs in ALDO/SALT-treated rats. miR-21 downregulation exacerbated ALDO/SALT-mediated cardiac hypertrophy, expression of fibrosis marker genes, 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.
(Copyright © 2017 Endocrine Society.)

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P20 GM103476 United States GM NIGMS NIH HHS; K08 DK099415 United States DK NIDDK NIH HHS; P01 HL051971 United States HL NHLBI NIH HHS; P20 GM104357 United States GM NIGMS NIH HHS; R01 HL066072 United States HL NHLBI NIH HHS; P30 GM103328 United States GM NIGMS NIH HHS; P20 GM121334 United States GM NIGMS NIH HHS

0 (MicroRNAs)
451W47IQ8X (Sodium Chloride)
4964P6T9RB (Aldosterone)

Date Created: 20170404 Date Completed: 20170907 Latest Revision: 20181113

20231215

PMC5460923

10.1210/en.2016-1707

28368454