Microrna-21 ablation exacerbates aldosterone-mediated cardiac injury, remodeling, and dysfunction

Maryam Syed, Jana P. Ball, Keisa Mathis, Michael E. Hall, Michael J. Ryan, Marc E. Rothenberg, Licy L. Yanes Cardozo, Damian G. Romero

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)E1154-E1167
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume315
Issue number6
DOIs
StatePublished - 1 Dec 2018

Fingerprint

Aldosterone
MicroRNAs
Wounds and Injuries
Salts
Hyperaldosteronism
Cardiomegaly
Fibrosis
Pathology
Hypertension
Inflammation
Small Untranslated RNA
Renin-Angiotensin System
Adrenal Glands
Cardiac Myocytes
Knockout Mice
Drinking Water
Genes
Heart Ventricles
Theoretical Models
Blood Pressure

Keywords

  • Aldosterone
  • Cardiac injury
  • Gene expression
  • MicroRNAs
  • Mineralocorticoids

Cite this

Syed, Maryam ; Ball, Jana P. ; Mathis, Keisa ; Hall, Michael E. ; Ryan, Michael J. ; Rothenberg, Marc E. ; Yanes Cardozo, Licy L. ; Romero, Damian G. / Microrna-21 ablation exacerbates aldosterone-mediated cardiac injury, remodeling, and dysfunction. In: American Journal of Physiology - Endocrinology and Metabolism. 2018 ; Vol. 315, No. 6. pp. E1154-E1167.
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abstract = "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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Microrna-21 ablation exacerbates aldosterone-mediated cardiac injury, remodeling, and dysfunction. / Syed, Maryam; Ball, Jana P.; Mathis, Keisa; Hall, Michael E.; Ryan, Michael J.; Rothenberg, Marc E.; Yanes Cardozo, Licy L.; Romero, Damian G.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 315, No. 6, 01.12.2018, p. E1154-E1167.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Microrna-21 ablation exacerbates aldosterone-mediated cardiac injury, remodeling, and dysfunction

AU - Syed, Maryam

AU - Ball, Jana P.

AU - Mathis, Keisa

AU - Hall, Michael E.

AU - Ryan, Michael J.

AU - Rothenberg, Marc E.

AU - Yanes Cardozo, Licy L.

AU - Romero, Damian G.

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AB - 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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