NOX4-driven mitochondrial oxidative stress in aging promotes myocardial remodeling and increases susceptibility to ventricular tachyarrhythmia.

Roberto Ramos Mondragon, Shuyun Wang, Mark D Stevenson, Andrey Lozhkin, Aleksandr E Vendrov, Lori L Isom, Marschall S Runge, Nageswara R Madamanchi

Department of Pharmacology, University of Michigan, 1150 West Medical Center Dr., 2301 Medical Science Research Building III, Ann Arbor, MI, 48109, USA.Department of Pharmacology, University of Michigan, 1150 West Medical Center Dr., 2301 Medical Science Research Building III, Ann Arbor, MI, 48109, USA. · pubmed

Paper

Abstract

Aging-associated mitochondrial oxidative stress has been implicated in ventricular tachyarrhythmias (VT), but the specific proarrhythmic mechanisms of mitochondrial pro-oxidative systems remain unclear. NADPH oxidase 4 (NOX4) expression in the heart increases with age, leading to mitochondrial oxidative stress, dysfunction, and adverse myocardial remodeling. This study investigated the susceptibility to aging-associated ventricular arrhythmia and the associated triggers and substrates using transgenic mice with mitochondria-targeted Nox4 overexpression (Nox4TG mice). Nox4TG mice showed a significantly higher incidence of pacing-induced VT, associated with shorter action potential duration (APD) due to increased transient outward potassium currents. Fractional sarcoplasmic reticulum (SR) Ca

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Research summary

The paper claims that NOX4-driven mitochondrial oxidative stress in aging increases susceptibility to ventricular tachyarrhythmia. This research is relevant as it investigates the underlying mechanisms of aging-related cardiac dysfunction, which could contribute to understanding and potentially mitigating age-related diseases.

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