Abstract 3731: Overlapping Patterns of Gene Expression in Experimental and Clinical Models of Myocardial Recovery
Background: Similar patterns of myocardial gene expression occur following beneficial pharmacological and/or device therapies for heart failure, suggesting that there may be specific ensembles of genes that promote myocardial recovery (MyoRec).
Purpose/Methods: We previously developed and characterized a tetracycline responsive transgenic model (ttA-MHCminTetO-TRAF2 mice) that allows for conditional cardiac restricted over expression of tumor necrosis factor receptor associated factor 2 (TRAF2), which we have shown is responsible for progressive left ventricular (LV) remodeling in cardiac inflammation. The ttA-MHCminTetO-TRAF2 mice develop LV remodeling by 8 weeks of age. Oral administration of dox for 4 weeks allows for complete LV reverse remodeling (MyoRec) in the ttA-TRAF2 mice (age 12 weeks), whereas “no dox” mice undergo progressive LV dilation (age 12 weeks). We performed a gene array in the hearts of wild-type and ttA-MHCminTetO-TRAF2 mice that were given dox or no dox. Changes in the patterns of gene expression were then compared to published (Circ. Res. 2005; 96: 592–599) changes in the human gene expression before and after support with a left ventricular assist device (LVAD).
Results: There were 748 genes that were differentially expressed (403 upregulated, 345 downregulated) in the ttA-MHCminTetO-TRAF2/no dox (LV remodeling) compared to ttA-MHCminTetO-TRAF2/dox mice (MyocRec). Gene Ontology (GO) classification of the genes that were involved in MyoRec showed remarkable overlap with the patterns observed in human LVAD samples (table⇓).
Conclusions: These data suggest that there are specific ensembles of genes may be responsible for myocardial recovery, which opens the possibility for developing therapeutic approaches that are specifically designed to promote myocardial recovery.