Mitochondrial oxidative stress contributes to diastolic dysfunction through impaired mitochondrial dynamics.

ABSTRACT: Diastolic dysfunction (DD) underlies heart failure with preserved ejection fraction (HFpEF), a clinical syndrome associated with aging that is becoming more prevalent. Despite extensive clinical studies, no effective treatment exists for HFpEF. Recent findings suggest that oxidative stress contributes to the pathophysiology of DD, but molecular mechanisms underpinning redox-sensitive cardiac remodeling in DD remain obscure. Using transgenic mice with mitochondria-targeted NOX4 overexpression (Nox4TG618) as a model, we demonstrate that NOX4-dependent mitochondrial oxidative stress induces DD in mice as measured by increased E/E', isovolumic relaxation time, Tau Glantz and reduced dP/dt_min while EF is preserved. In Nox4TG618 mice, fragmentation of cardiomyocyte mitochondria, incre

SUBMITTER: Lozhkin A 

PROVIDER: S-EPMC9530618 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature