Mitochondrial 4-HNE derived from MAO-A promotes mitoCa²⁺ overload in chronic postischemic cardiac remodeling.

ABSTRACT: Chronic remodeling postmyocardial infarction consists in various maladaptive changes including interstitial fibrosis, cardiomyocyte death and mitochondrial dysfunction that lead to heart failure (HF). Reactive aldehydes such as 4-hydroxynonenal (4-HNE) are critical mediators of mitochondrial dysfunction but the sources of mitochondrial 4-HNE in cardiac diseases together with its mechanisms of action remain poorly understood. Here, we evaluated whether the mitochondrial enzyme monoamine oxidase-A (MAO-A), which generates H₂O₂ as a by-product of catecholamine metabolism, is a source of deleterious 4-HNE in HF. We found that MAO-A activation increased mitochondrial ROS and promoted local 4-HNE production inside the mitochondria through cardiolipin peroxidation in primary

SUBMITTER: Santin Y 

PROVIDER: S-EPMC7244724 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature