Abstract 17729: Expression Profiles of Circulating MicroRNA in Heart Failure With Reduced and Preserved Ejection Fraction in Asia Population
The important roles of microRNAs (miRNAs) in cardiovascular development and cardiac response to acute and chronic injury are increasingly being recognized. MiRNAs play important roles in cardiac diseases. Circulating miRNA signatures may offer diagnostic and pathogenic information. These circulating profiles in Heart Failure with Reduced (HFREF) or Preserved (HFPEF) ejection fraction remain to be defined.
We hypothesized that HFREF and HFPEF are associated with distinct circulating miRNA signatures that may offer insight into the underlying mechanisms distinguishing both phenotypes. MiRNA profiling was performed on plasma from 16 healthy controls, 18 HFREF and 13 HFPEF. MiRNAs levels were compared between healthy controls, HFREF, HFPEF and combined HF. The miRNAs that distinguished between HFREF and HFPEF were miR-103-2, -130b, -141, -143, -181c, -199a-5p, -200b, -223, -26b, -340 and -7-1 (p-values 0.001-0.049). Four such miRNAs were miR-130b, -143, -200b and -7-1 were highly differentially regulated in HFPEF as compared to control (p-values 0.001-0.03). The miRNAs that distinguished HFREF from control were let-7f, miR-103, -145, -193b and -339-5p (p-values 0.01-0.049). The miRNAs distinguished HF from control were let-7d, miR-126, -143, -181a, -30b, -30d, -345 and -376b (p-values 0.001-0.042). These miRNAs signatures with highly predicted target associated with neurohormone were selected for ongoing validation in a larger sample size study. MiR-143 with the predicted targets of natriuretic peptide B (BNP) and natriuretic peptide receptor C (NPR3) was found to be highly dysregulated in in-vitro model. Cardiomyocytes were subjected to hypoxic condition at 0.2 % of oxygen over 2 and 120 hours. MiR-143 expression was significantly regulated in correlation with NPR3 level. Ongoing functional assay will further decipher the biological function of miR-143.
This study shows specific plasma miRNA signatures that could be valuable biomarkers to distinguish between HFREF and HFPEF and from control. This is the first study in Asia to undertake a comparison of miRNA profiles in patients of these two phenotypes. Further study in in-vitro model on miR-143 deciphers the plausible underlying mechanism that can lead to HF.
- © 2013 by American Heart Association, Inc.