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TRIF/miR-34a mediates aldosterone-induced cardiac inflammation and remodeling.
- Source :
-
Clinical Science . Jun2020, Vol. 134 Issue 12, p1319-1331. 13p. - Publication Year :
- 2020
-
Abstract
- Aldosterone, as a major product of renin-angiotensin-aldosterone system (RAAS), determines multiple pathophysiological processes in cardiovascular diseases. The excess inflammatory response is one of the key profiles in aldosterone-mediated cardiac remodeling. However, the potential mechanisms of aldosterone/inflammatory signaling were still not fully disclosed. The present study aimed to investigate whether TIR-domain-containing adapter-inducing interferon-ß (Trif) participated in the aldosterone-induced cardiac remodeling, and to explore potential molecular mechanisms. Trif knockout mice and their littermates were osmotically administrated with aldosterone (50 µg/kg per day) for 21 and 42 days. The cardiac structural analysis, functional parameters, and mitochondrial function were measured. Aldosterone dose- or time-dependently increased the levels of TRIF in primary mouse cardiomyocytes or mouse heart tissues. Trif deficiency protected against aldosterone-induced cardiac hypertrophy, fibrosis and dysfunction. Moreover, Trif deficiency also suppressed aldosterone-induced cardiac inflammatory response and mitochondrial injuries. Mechanistically, overexpression of cardiac microRNAs (miR)-34a reversed the cardiac benefits of Trif deficiency in aldosterone-treated mice. Taken together, Trif/miR-34a axis could provide a novel molecular mechanism for explaining aldosterone-induced cardiac hypertrophy, fibrosis and functional disorders. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01435221
- Volume :
- 134
- Issue :
- 12
- Database :
- Academic Search Index
- Journal :
- Clinical Science
- Publication Type :
- Academic Journal
- Accession number :
- 144398822
- Full Text :
- https://doi.org/10.1042/CS20200249