Bibliographic Details
| Title: |
Divergent cardiac and renal effects of miR-181c-5p inhibition in a rodent heart failure model |
| Authors: |
Jente R. A. Boen, Andreas B. Gevaert, Amélie Dendooven, Dustin Krüger, Michiel Tubeeckx, Jens Van Fraeyenhove, Tine Bruyns, Vincent F. M. Segers, Emeline M. Van Craenenbroeck |
| Source: |
Frontiers in Cardiovascular Medicine, Vol 11 (2024) |
| Publisher Information: |
Frontiers Media S.A., 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Diseases of the circulatory (Cardiovascular) system |
| Subject Terms: |
heart failure, miR-181c-5p, renal dysfunction, thrombotic microangiopathy, fibrosis, diastolic dysfunction, Diseases of the circulatory (Cardiovascular) system, RC666-701 |
| More Details: |
AimsMiR-181c-5p overexpression associates with heart failure (HF) and cardiac damage, but the underlying pathophysiology remains unclear. This study investigated the effect of miR-181c-5p inhibition on cardiac function and fibrosis in a rodent model of diastolic dysfunction, and evaluated additional effects on kidney as relevant comorbid organ.Methods and resultsDiastolic dysfunction was induced in male C57/BL6J mice (n = 20) by combining high-fat diet, L-NG-nitroarginine methyl ester, and angiotensin II administration, and was compared to sham controls (n = 18). Mice were randomized to subcutaneous miR-181c-5p antagomiR (INH) or scrambled antagomiR injections (40 mg/kg/week). HF mice demonstrated diastolic dysfunction and increased fibrosis, which was attenuated by INH treatment. Remarkably, HF + INH animals had a threefold higher mortality rate (60%) compared to HF controls (20%). Histological examination revealed increased glomerular damage in all INH treated mice, and signs of thrombotic microangiopathy (TMA) in mice who died prematurely. Quantitative polymerase chain reaction demonstrated a miR-181c-5p-related downregulation of cardiac but not renal Tgfbr1 in HF + INH mice, while INH treatment reduced renal but not cardiac Vegfa expression in all mice.ConclusionThis study demonstrates cardiac anti-fibrotic effects of miR-181c-5p inhibition in a rodent HF model through targeting of Tgfbr1 in the heart. Despite improved diastolic function, HF + INH mice had higher mortality due to increased predisposition for TMA, increased renal fibrosis and glomerular damage, associated with Vegfa downregulation in kidneys. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2297-055X |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fcvm.2024.1383046/full; https://doaj.org/toc/2297-055X |
| DOI: |
10.3389/fcvm.2024.1383046 |
| Access URL: |
https://doaj.org/article/cae434e6b83d432aa3c619f3a34d5a6b |
| Accession Number: |
edsdoj.434e6b83d432aa3c619f3a34d5a6b |
| Database: |
Directory of Open Access Journals |
