Advantages and disadvantages of the chemogenetic model of heart failure
The chemogenetic approach used to generateH2O2 in the heart has resulted in a robust and easily manipulated model for cardiac dysfunction that may lead to development of new therapeutic targets to treat or prevent heart failure. The chemogenetic model of heart failure recapitulates many commonly observed features of human heart failure and allows us to distinguish cardiac myocyte-specific pathology from the pleiotropic changes characteristic of other ”interventional” animal models of heart failure. While these observations help to prove causality , this does not establish that oxidative stress is the only cause and isnecessary for development of heart failure. Indeed, the broad spectrum of heart failure syndromes suggests that oxidative stress may play a central role in some forms of heart failure but be less important in others. We acknowledge that intracellular generation of cytosolic H2O2 by a recombinant yeast enzyme in cardiac myocytes does not necessarily recapitulate all the complex alterations in cardiac and systemic redox metabolism that are associated with cardiomyopathies in human patients. Despite these limitations, chemogenetic approaches have been used to devise an informative and tractable new animal model of heart failure caused by oxidative stress. Further study of his robust and reversible animal model may lead to the identification of novel therapeutic targets for the prevention and treatment of heart failure.
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