Journalartikel

Jahr der Veröffentlichung: 2019

Zeitschrift: Scientific Reports

Bandnummer: 9

ISSN: 2045-2322

Open Access Status: Gold

DOI Link: https://doi.org/10.1038/s41598-019-49231-9

Verlag: Nature Research

Abstract: 
Constitutive expression of the chemokine Mcp1 in mouse cardiomyocytes creates a model of inflammatory cardiomyopathy, with death from heart failure at age 7-8 months. A critical pathogenic role has previously been proposed for induced oxidative stress, involving NADPH oxidase activation. To test this idea, we exposed the mice to elevated oxygen levels. Against expectation, this prevented, rather than accelerated, the ultrastructural and functional signs of heart failure. This result suggests that the immune signaling initiated by Mcp1 leads instead to the inhibition of cellular oxygen usage, for which mitochondrial respiration is an obvious target. To address this hypothesis, we combined the Mcp1 model with xenotopic expression of the alternative oxidase (AOX), which provides a sink for electrons blocked from passage to oxygen via respiratory complexes III and IV. Ubiquitous AOX expression provided only a minor delay to cardiac functional deterioration and did not prevent the induction of markers of cardiac and metabolic remodeling considered a hallmark of the model. Moreover, cardiomyocyte-specific AOX expression resulted in exacerbation of Mcp1-induced heart failure, and failed to rescue a second cardiomyopathy model directly involving loss of cIV. Our findings imply that mitochondria! involvement in the pathology of inflammatory cardiomyopathy is multifaceted and complex.

Harvard-Zitierstil: Dhandapani, P., Begines-Moreno, I., Brea-Calvo, G., Gaertner, U., Graeber, T., Javier Sanchez, G., et al. (2019) Hyperoxia but not AOX expression mitigates pathological cardiac remodeling in a mouse model of inflammatory cardiomyopathy, Scientific Reports, 9, Article 12741. https://doi.org/10.1038/s41598-019-49231-9

APA-Zitierstil: Dhandapani, P., Begines-Moreno, I., Brea-Calvo, G., Gaertner, U., Graeber, T., Javier Sanchez, G., Morty, R., Schoenig, K., tenHoeve, J., Wietelmann, A., Braun, T., Jacobs, H., & Szibor, M. (2019). Hyperoxia but not AOX expression mitigates pathological cardiac remodeling in a mouse model of inflammatory cardiomyopathy. Scientific Reports. 9, Article 12741. https://doi.org/10.1038/s41598-019-49231-9