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Chemogenetic generation of hydrogen peroxide in the heart induces severe cardiac dysfunction.

ABSTRACT: Oxidative stress plays an important role in the pathogenesis of many disease states. In the heart, reactive oxygen species are linked with cardiac ischemia/reperfusion injury, hypertrophy, and heart failure. While this correlation between ROS and cardiac pathology has been observed in multiple models of heart failure, the independent role of hydrogen peroxide (H₂O₂) in vitro and in vivo is unclear, owing to a lack of tools for precise manipulation of intracellular redox state. Here we apply a chemogenetic system based on a yeast D-amino acid oxidase to show that chronic generation of H₂O₂ in the heart induces a dilated cardiomyopathy with significant systolic dysfunction. We anticipate that chemogenetic approaches will enable future studies of in vivo H₂O₂ signaling not only in the heart, but also in the many other organ systems where the relationship between redox events and physiology remains unclear.

SUBMITTER: Steinhorn B

PROVIDER: S-EPMC6168530 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Chemogenetic generation of hydrogen peroxide in the heart induces severe cardiac dysfunction.

Steinhorn Benjamin B Sorrentino Andrea A Badole Sachin S Bogdanova Yulia Y Belousov Vsevolod V Michel Thomas T

Nature communications 20181002 1

Oxidative stress plays an important role in the pathogenesis of many disease states. In the heart, reactive oxygen species are linked with cardiac ischemia/reperfusion injury, hypertrophy, and heart failure. While this correlation between ROS and cardiac pathology has been observed in multiple models of heart failure, the independent role of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) in vitro and in vivo is unclear, owing to a lack of tools for precise manipulation of intracellular redox sta ...[more]

PMID: 30279532

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