Abstract 12427: Plasma microRNA in Patients with Hypertensive Heart Disease: Differential Expression in Left Ventricular Hypertrophy versus Diastolic Heart Failure

Background: MicroRNAs (miRs) are small noncoding RNAs that associate with target mRNAs and act as regulators of gene expression by promoting mRNA degradation or inhibiting translation. Animal models suggest that miRs play a translational or post-translational regulatory role in myocardial growth, fibrosis, and remodeling. However, whether specific miRs are differentially expressed in patients with LV hypertrophy (LVH) or diastolic heart failure (DHF) is unknown. The current study tested the hypothesis that plasma miRs could be reliably measured in patients and that there is selective regulation of specific miRs with LVH vs. DHF. Methods and Results: Plasma miR, echocardiography, 6 minute hall walk (6MHW) were measured in controls (CTL n=15) and patients with LVH but no DHF (n=13, LVH), and patients with LVH and DHF (n=13, DHF). DHF patients had shorter 6MHW, increased pulmonary wedge pressures, and increased nt-proBNP compared with CTL or LVH patients. Selected miRs (miR-1, -21, -29a, 133a, 760) were measured using quantitative rt-PCR and normalized for endogenous snRNA U6 which served as a control (Table). Coefficient of variation for all miRs was less than 10%. In LVH, there were increases in miR-21 (augment hypertrophic growth), and increased miR-1, 29a, 133a, and 760 (limit fibrosis). In DHF, this compensatory response in miRs was lost; all miRs were similar to CTL possibly facilitating the increased fibrosis and less growth induction characteristic of DHF. Conclusions: A unique profile of miRs was upregulated in patients with LVH; however, this compensatory response at the level of translational regulation was lost in patients who had developed DHF. Changes in miRs could serve as a novel biomarker identifying a molecular signature which reflects a change in translational regulation in patients making the transition from hypertrophy to heart failure.