Reversal of heart failure in a chemogenetic model of persistent cardiac redox stress.

Reversal of heart failure in a chemogenetic model of persistent cardiac redox stress. Am J Physiol Heart Circ Physiol. 2019 Jul 12;: Authors: Sorrentino A, Steinhorn B, Troncone L, Saravi SS, Badole SL, Eroglu E, Kijewski MF, Divakaran S, Di Carli M, Michel T Abstract We previously described a novel "chemogenetic" animal model of heart failure that recapitulates a characteristic feature commonly found in human heart failure: chronic oxidative stress. This heart failure model uses a chemogenetic approach to activate a recombinant yeast D-amino acid oxidase in rat hearts in vivo in order to generate oxidative stress, which then rapidly leads to the development of a dilated cardiomyopathy. Here we apply this new model to drug testing by studying its response to treatment with the angiotensin-II (Ang-II) receptor blocker valsartan, administered either alone or with the neprilysin inhibitor sacubitril. Echocardiographic and F18-deoxyglucose positron emission tomographic imaging revealed that valsartan in the presence or absence of sacubitril reverses the anatomical and metabolic remodeling induced by chronic oxidative stress. Markers of oxidative stress, mitochondrial function, and apoptosis- as well as classical heart failure biomarkers- also normalize following drug treatments despite the persistence of cardiac fibrosis. These findings provide evidence that chemogenetic heart failure is rapidly reversible by drug treatment, setting the ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research