Dynamic changes of serum microRNA-122-5p through therapeutic courses indicates amelioration of acute liver injury accompanied by acute cardiac decompensation

Abstract

Aims: Recent studies have shown that serum microRNA (miR) abundance is informative for the diagnosis or prognosis of heart failure. However, the dynamics and kinetics of miRs in acute heart failure are largely unknown. Serial measurement and analysis of serum miRs changes in individuals along their therapeutic course could reduce inter-individual variation and should detect potentially important serum miRs related to disease mechanisms. Based on this concept, we profiled serum miR signatures of blood samples that were obtained sequentially on the day of admission and on hospital Day 7. Methods and results: This prospective, observational study included 42 consecutive acute heart failure patients (74 ± 1 years old, 24 male). From admission to Day 7, most of the patients showed clinical improvement. In such a cohort, we detected several fluctuations of serum miRs by two distinct screening methods (quantitative PCR and high-throughput sequencing). One of these fluctuating serum miRs, miR-122-5p, decreased significantly from Day 1 to Day 7 [median arbitrary unit (1st:3rd quantile value); 4.62 [2.39:12.3] to 3.07 [1.67:5.39], P = 0.007]. This fluctuation was significantly correlated with changes in serum liver function markers (estimated coefficient and 95% confidence interval; vs change in aspartate aminotransferase 1.69, 0.890–2.484, P < 0.001 and r = 0.560, vs change in alanine aminotransferase 1.09, 0.406–1.771, P = 0.007 and r = 0.428). Conclusions: The serum miR signature of patients with acute heart failure might indicate the severity of the disease or patients' response to therapeutic intervention. Notably, serum miR-122-5p levels reflect liver damage in this condition.