Heart specific knockout of Ndufs4 ameliorates ischemia reperfusion injury.

ABSTRACT:

Rationale

Ischemic heart disease (IHD) is a leading cause of mortality. The most effective intervention for IHD is reperfusion, which ironically causes ischemia reperfusion (I/R) injury mainly due to oxidative stress-induced cardiomyocyte death. The exact mechanism and site of reactive oxygen species (ROS) generation during I/R injury remain elusive.

Objective

We aim to test the hypothesis that Complex I-mediated forward and reverse electron flows are the major source of ROS in I/R injury of the heart.

Methods and results

We used a genetic model of mitochondrial Complex I deficiency, in which a Complex I assembling subunit, Ndufs4 was knocked out in the heart (Ndufs4H-/-). The Langendorff perfused Ndufs4H-/- hearts exhibited significantly reduced infarct size (45.3 ± 

SUBMITTER: Zhang H 

PROVIDER: S-EPMC6192835 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature