Abstract
Excess aldosterone (ALDO) causes hypertension and cardiac hypertrophy, inflammation and fibrosis that lead to cardiac dysfunction. We previously reported that ALDO/SALT increases left ventricle (LV) miR‐21 expression, but whether this upregulation is protective, deleterious or a bystander is unknown. We used mice with genetic ablation of miR‐21 to study its role in ALDO/SALT‐mediated cardiac hypertrophy, fibrosis and dysfunction.Uninephrectomized male miR‐21 knockout (miR21KO) or wild‐type (WT) mice were treated with ALDO (0.15 µg/h) and SALT (1.0 % NaCl + 0.3 % KCl) or vehicle for 2 or 8 weeks (N=24/group). Analysis of cardiac tissue by weight and WGA staining revealed ALDO/SALT exacerbated LV hypertrophy (4.6 vs. 4.1 mg/g BW, p<0.05) and LV cardiomyocyte cross‐sectional area (208 vs. 195 µm2, p<0.01) in miR21KO vs. WT mice, respectively. Upregulation of fibrosis markers (Ctgf, collagen I, collagen III, fibronectin, lysyl oxidase), quantified by qRT‐PCR, was exacerbated by ALDO/SALT in miR21KO LV (2‐ to 7‐fold, p<0.05) vs. WT mice. Interstitial (0.46 vs. 0.35 %, p<0.05) and perivascular (0.32 vs. 0.27 %, p<0.05) fibrosis, determined by picrosirius red staining, was exacerbated by ALDO/SALT in miR21KO vs. WT mice. Blood pressure (BP), measured by indwelling carotid artery catheters in conscious mice, was raised to similar levels by ALDO/SALT in miR21KO vs. WT mice.Our results show that miR‐21 ablation exacerbates ALDO/SALT‐mediated cardiac hypertrophy, fibrosis and dysfunction independently of BP, suggesting that therapies that increase cardiac levels of miR‐21 may benefit patients with excess ALDO.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.