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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