# The Knockout of PEX11a Results in Mild Peroxisomal Dysfunction and Lowered Cardiac Recovery Following Langendorff-Mediated Ischemia–Reperfusion in Mice

## TL;DR

Removing PEX11a in mice leads to small peroxisomal issues and worse heart recovery after simulated heart attacks.

## Contribution

This study reveals that mild peroxisomal dysfunction can impair cardiac recovery after ischemia-reperfusion.

## Key findings

- Pex11a−/− cardiomyocytes show altered morphology and lipid composition.
- Pex11a−/− hearts exhibit reduced recovery after ischemia-reperfusion.
- Altered gene expression and lipid shifts were observed in Pex11a−/− cardiomyocytes.

## Abstract

What are the main findings?
Cardiomyocytes from Pex11a−/− mice display altered morphology and lipid composition.After in vitro ischemia/reperfusion, the recovery of Pex11a−/− hearts was lowered.

Cardiomyocytes from Pex11a−/− mice display altered morphology and lipid composition.

After in vitro ischemia/reperfusion, the recovery of Pex11a−/− hearts was lowered.

What are the implications of the main findings?
The precise function of peroxisomes in cardiomyocytes requires further elucidation.Peroxisomes might preserve cardiomyocyte functionality during and after ischemia/reperfusion injury.

The precise function of peroxisomes in cardiomyocytes requires further elucidation.

Peroxisomes might preserve cardiomyocyte functionality during and after ischemia/reperfusion injury.

Peroxisomal biogenesis defects frequently trigger processes of remodeling, increased oxidative stress and metabolic dysregulations that cause cellular dysfunction. Despite extensive research into cardiomyocyte ultrastructure and metabolism, knowledge on peroxisomal function in these cells is scarce. The objective of this study was therefore to investigate the impact of the purportedly asymptomatic (mild) deficiency of the peroxisomal biogenesis protein PEX11a on cardiomyocyte structure and cardiac function in mice. Langendorff-reperfusion experiments revealed diminished post-ischemic recovery following Pex11a knockout suggesting compromised cardiac response to ischemic stress. The suboptimal recovery might be attributable to increased ischemia-induced tissue deterioration consequent to morphological and metabolic abnormalities of the cardiomyocytes. Indeed, several alterations were observed in these cells in Pex11a knockout mice: (i) augmented size and number of peroxisomes and lipid droplets; (ii) increased sarcomere length; (iii) altered gene expression of peroxisome proliferator-activated receptors, organellar fission machinery proteins and cardiac markers; and (iv) a lipid composition shift. We hypothesized that peroxisomes contribute to the preservation of cardiomyocyte structure and functionality under conditions of ischemia–reperfusion. We further proposed that even “mild”, undiagnosed peroxisomal defects can significantly impact cardiac performance following ischemia. This poses novel challenges for the risk assessment of cardiac pathologies.