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MicroRNA-21 ablation exacerbates aldosterone-mediated cardiac injury, remodeling, and dysfunction.
Syed, Maryam; Ball, Jana P; Mathis, Keisa W; Hall, Michael E; Ryan, Michael J; Rothenberg, Marc E; Yanes Cardozo, Licy L; Romero, Damian G.
Afiliación
  • Syed M; Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, Mississippi.
  • Ball JP; Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, Mississippi.
  • Mathis KW; Department of Physiology and Biophysics, University of Mississippi Medical Center , Jackson, Mississippi.
  • Hall ME; Department of Physiology and Biophysics, University of Mississippi Medical Center , Jackson, Mississippi.
  • Ryan MJ; Department of Medicine, University of Mississippi Medical Center , Jackson, Mississippi.
  • Rothenberg ME; Department of Physiology and Biophysics, University of Mississippi Medical Center , Jackson, Mississippi.
  • Yanes Cardozo LL; Women's Health Research Center, University of Mississippi Medical Center , Jackson, Mississippi.
  • Romero DG; Cardio Renal Research Center, University of Mississippi Medical Center , Jackson, Mississippi.
Am J Physiol Endocrinol Metab ; 315(6): E1154-E1167, 2018 12 01.
Article en En | MEDLINE | ID: mdl-30153065
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.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Cardiomegalia / Miocitos Cardíacos / MicroARNs / Aldosterona / Hiperaldosteronismo Límite: Animals Idioma: En Revista: Am J Physiol Endocrinol Metab Asunto de la revista: ENDOCRINOLOGIA / FISIOLOGIA / METABOLISMO Año: 2018 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Cardiomegalia / Miocitos Cardíacos / MicroARNs / Aldosterona / Hiperaldosteronismo Límite: Animals Idioma: En Revista: Am J Physiol Endocrinol Metab Asunto de la revista: ENDOCRINOLOGIA / FISIOLOGIA / METABOLISMO Año: 2018 Tipo del documento: Article