Affiliation:
1. Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
2. The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Heilongjiang Province, Harbin 150086, China
Abstract
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-β (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.
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