Load-Dependent Changes in Left Ventricular Gene Expression in a Pathophysiologically Relevant Murine Model of Reversible Heart Failure (2 weeks heart failure, 4 weeks reversal)

Wild type, female, C57BL/6 mice were subjected to sham (n=6) surgery, or TAC + MI to cause progressive LV remodeling (n=12). At 2wks post-TAC, one group of mice underwent de-banding (HF-DB, n=6), whereas in a second group of mice the band remained intact (HF; n = 6). LV remodeling was evaluated by 2D echocardiography at 14 days post-TAC+MI , and 4 wks post-debanding. At 6 wks the hearts were excised and analyzed for changes in gene expression using transcriptional profiling. e-banding in the HF-DB mice resulted in normalization of LV volumes and LV mass, and normalization of cardiac myocyte hypertrophy at 6wks, without significant changes in myofibrillar collagen in the HF and HF-DB mice. Both LV ejection fraction (LVEF) and LV radial strain improved numerically following de-banding; however, both measurements remained significantly depressed in the HF-DB mice compared to sham, and were not significantly different from HF mice at 6wks. Reverse LV remodeling in the HF-DB mouse hearts was accompanied by a partial (80%) normalization of the genes that became dysregulated during LV remodeling, whereas 20% of genes remained persistently dysregulated following reverse LV remodeling. Gene expression in mouse cardiac left ventricular samples was measured after 6 wk of sustained transverse aortic constriction + small apical myocardial infarction (TAC+MI) (HF group), after 2 wk of TAC+MI with 4 wk of de-banding (HF_DB), and in time-matched animals subjected to sham surgeries both for TAC+MI initiation and for de-banding. 6 individual mice were used per group.