title: Role and Regulation of MicroRNAs in Aldosterone-Mediated Cardiac Injury and Dysfunction in Male Rats.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Mississippi Medical Center, Jackson, Mississippi 39216.
authors.forename: Jana P
authors.initials: JP
authors.lastname: Ball
authors.affiliation: Department of Biochemistry, University of Mississippi Medical Center, Jackson, Mississippi 39216.
authors.forename: Maryam
authors.initials: M
authors.lastname: Syed
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216.|Cardio-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi 39216.|Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi 39216.
authors.forename: Rodrigo O
authors.initials: RO
authors.lastname: Marañon
authors.affiliation: Cardio-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi 39216.|Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi 39216.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Hall
authors.affiliation: Department of Biochemistry, University of Mississippi Medical Center, Jackson, Mississippi 39216.
authors.forename: Roshan
authors.initials: R
authors.lastname: Kc
authors.affiliation: Department of Biochemistry, University of Mississippi Medical Center, Jackson, Mississippi 39216.|Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216.|Cardio-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi 39216.|Women's Health Research Center, University of Mississippi Medical Center, Jackson, Mississippi 39216.
authors.forename: Jane F
authors.initials: JF
authors.lastname: Reckelhoff
authors.affiliation: Cardio-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi 39216.|Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi 39216.|Women's Health Research Center, University of Mississippi Medical Center, Jackson, Mississippi 39216.
authors.forename: Licy L
authors.initials: LL
authors.lastname: Yanes Cardozo
authors.affiliation: Department of Biochemistry, University of Mississippi Medical Center, Jackson, Mississippi 39216.|Cardio-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi 39216.|Women's Health Research Center, University of Mississippi Medical Center, Jackson, Mississippi 39216.
authors.forename: Damian G
authors.initials: DG
authors.lastname: Romero
mesh_terms: D000450:Aldosterone / Q000009:adverse effects*; D000818:Animals; D005786:Gene Expression Regulation; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006331:Heart Diseases / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology*; D006929:Hyperaldosteronism / Q000150:complications* / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
chemical_list: D035683:MicroRNAs; D012965:Sodium Chloride; D000450:Aldosterone