Abstract 12719: Expression of DHRS7c, A Novel Cardiomyocyte-expressed Gene Affected by Adrenergic Stimulation, is Strongly Associated With Ventricular Reverse-remodeling in Dilated Cardiomyopathy
Background: The molecular mechanisms by which β-blockers produce ventricular reverse-remodeling in nonischemic dilated cardiomyopathy (NDCM) are incompletely understood. DHRS7C is a short chain dehydrogenase/reductase of uncertain functional significance expressed preferentially in the myocardium and down-regulated in heart failure or with α- and β-adrenergic stimulation. The objective of this study was to determine the association of DHRS7C with DCM and reverse-remodeling in heart failure patients taking β-blockers.
Methods and Results: Forty-seven NDCM patients were randomized to metoprolol succinate, metoprolol + doxazosin, or carvedilol for 18 months. Ejection fractions (EFs) were measured by radionuclide ventriculography, and myocardial biopsy was performed at baseline, 3, and 12 months. Transcriptome-wide myocardial mRNA expression was measured using the Affymetrix HGU133 plus 2.0 GeneChip. DHRS7C expression was significantly reduced in DCM patients compared with 4 non-failing controls (7.3±0.2 vs. 9.0±0.7, p=0.03). Thirty-one (66%) patients had a reverse-remodeling response defined as improvement of 8 LVEF units at 12 months or if not available, 5 LVEF units at 3 months. DHRS7C was significantly more up-regulated in responders vs. non-responders (4.1±0.6 vs. 2.2±0.7 fold change, p=0.03). Change in gene expression was significantly correlated with change in LVEF (r=0.52, p<0.001), RVEF (r=0.40, p<0.001), and heart rate (r=-0.38, p<0.01). These correlations were comparable to other genes associated with reverse-remodeling.
Conclusions: Myocardial expression of DHRS7C is significantly down-regulated in human NDCM. As expected, expression increases in response to β-AR blockade and is strongly correlated with both EF and heart rate response to beta-blockers comparable to MYH6 and ADRB1/2. Although its function is unclear, DHRS7C may be an important biomarker or mechanistically important for ventricular reverse-remodeling.
Author Disclosures: D.P. Kao: Consultant/Advisory Board; Modest; Gliimpse, Inc.. B.D. Lowes: None. E.M. Gilbert: None. W. Minobe: None. L.K. Meyer: None. R.A. Quaife: None. M.R. Bristow: Employment; Significant; ARCA biopharma. Ownership Interest; Significant; ARCA biopharma.
- © 2015 by American Heart Association, Inc.