TRIF/miR-34a mediates aldosterone-induced cardiac inflammation and remodeling.

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-beta (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 mu g/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.