Key result
Novel chemogenetic heart failure model dynamically manipulates myocyte redox stress to yield valsartan-responsive dilated cardiomyopathy.
Why the study?
Many current animal models of heart failure are hampered by intrinsic methodological complexities or yield only subtle cardiac phenotypes even after prolonged in vivo treatments.
A novel chemogenetic animal model allows for dynamic, specific in vivo generation of ROS in cardiac myocytes to study oxidative stress and heart failure.
Hypothesis-generating for redox-targeted HF therapies; extends preclinical models without supporting practice change.
Many current animal models of heart failure are hampered by intrinsic methodological complexities, while other models yield only a subtle cardiac phenotype even after prolonged in vivo treatments. A new ‘chemogenetic’ animal model of heart failure reproduces a critical characteristic shared by many disease states that lead to heart failure in humans: an increase in redox stress in the heart. This ‘chemogenetic’ approach exploits a recombinant yeast enzyme that can be dynamically and specifically activated in vivo to generate the ROS hydrogen peroxide (H 2 O 2 ) in cardiac myocytes. Redox stress can be rapidly, selectively and reversibly manipulated by chemogenetic generation of ROS in cardiac myocytes, yielding a new model of dilated cardiomyopathy. Treatment of animals with the angiotensin receptor antagonist valsartan promotes recovery of ventricular function and resolution of adverse cardiac remodelling. This mini‐review discusses in vivo chemogenetic approaches to manipulate and analyse oxidative stress in the heart.
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Sorrentino et al. (2020) conducted a review in Heart failure. Chemogenetic generation of ROS was evaluated. A novel chemogenetic animal model of heart failure allows dynamic manipulation of redox stress in cardiac myocytes, yielding a dilated cardiomyopathy phenotype that is responsive to valsartan.
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