Abstract 16470: Identification of Microrna in an Ovine Model of Heart Failure
Introduction: The well-established ovine rapid-pacing model of heart failure (HF) reproduces the pathophysiology of acute human HF in terms of its hemodynamic, neurohormonal and renal profile. This model offers opportunities to investigate the molecular pathology of HF. MicroRNAs appear to influence many aspects of the molecular response to HF. Little is known of the regulation of microRNAs in sheep.
Hypothesis: Experimental ovine HF exhibits changes in microRNAs expression which reflects the concurrent derangement of hemodynamic and neurohormonal status.
Methods and results: Serial hemodynamic and neurohormonal measurements were performed in sheep during the development of severe HF (14 days of rapid left ventricular pacing at 225 bpm) and over 25 days recovery following cessation of pacing (HF-R). Left ventricular tissue from non-pacing Control (n=5), HF (n=4) and HF-R (n=3) were collected. In HF, cardiac output was reduced by 60% compared to Control (p<0.001), with return to non-paced baseline during recovery. Plasma atrial and brain natriuretic peptides increased 25-fold (p<0.01) and 10-fold (p<0.05) respectively with pacing (HF vs. Control), and decreased back to baseline levels over recovery. Plasma renin activity was enhanced 3.7-fold (p<0.05) during HF and reduced significantly over recovery. MicroRNAs profiling using hsa/mmu/rno microRNA microarray probes were performed and 846 microRNAs were detected across all samples. Stem-loop qPCR verification confirmed high consistence of overlapping microRNAs between array and qPCR (88%). 125 and 95 microRNAs were differentially expressed in HF and HF-R vs. Control respectively; and 69 in HF vs. HF-R (p<0.05, fold change±1.2). Among them 18 microRNAs were selected for verification. Of these, 13 microRNA dysregulations were verified in HF and HF-R vs. Control. In particular, miR-210 (associated with hypoxia-related pathway) was up-regulated 1.76-fold (p<0.001) in HF vs. Control and down-regulated 1.64-fold (p<0.05) in HF-R vs. HF, on return to baseline level.
Conclusion: We have demonstrated the feasibility of assessing sheep microRNAs with existing microRNA array and qPCR. Taking this approach, we offer the first report of dysregulation of microRNAs in the rapid-pacing ovine model of HF.
Author Disclosures: L. Wong: None. K. Lew: None. Q. Chen: None. M. Rademaker: None. L. Ellmers: None. C. Charles: None. A.M. Richards: None. P. Wang: None.
- © 2014 by American Heart Association, Inc.