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Depletion of cardiac cardiolipin synthase alters systolic and diastolic function

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Item Type:Article
Title:Depletion of cardiac cardiolipin synthase alters systolic and diastolic function
Creators Name:Smeir, E. and Leberer, S. and Blumrich, A. and Vogler, G. and Vasiliades, A. and Dresen, S. and Jaeger, C. and Gloaguen, Y. and Klose, C. and Beule, D. and Schulze, P.C. and Bodmer, R. and Foryst-Ludwig, A. and Kintscher, U.
Abstract:Cardiolipin (CL) is a major cardiac mitochondrial phospholipid maintaining regular mitochondrial morphology and function in cardiomyocytes. Cardiac CL production includes its biosynthesis and a CL remodeling process. Here we studied the impact of CL biosynthesis and the enzyme cardiolipin synthase (CLS) on cardiac function. CLS and cardiac CL species were significantly downregulated in cardiomyocytes following catecholamine-induced cardiac damage in mice, accompanied by increased oxygen consumption rates, signs of oxidative stress, and mitochondrial uncoupling. RNAi-mediated cardiomyocyte-specific knockdown of CLS in Drosophila melanogaster resulted in marked cardiac dilatation, severe impairment of systolic performance, and slower diastolic filling velocity assessed by fluorescence-based heart imaging. Finally, we showed that CL72:8 is significantly decreased in cardiac samples from patients with heart failure with reduced ejection fraction (HFrEF). In summary, we identified CLS as a regulator of cardiac function. Considering the cardiac depletion of CL species in HFrEF, pharmacological targeting of CLS may be a promising therapeutic approach.
Keywords:Animal Physiology, Lipidomics, Molecular Biology, Molecular Physiology, Animals, Mice, Drosophila melanogaster, Rats
Source:iScience
ISSN:2589-0042
Publisher:Cell Press
Volume:24
Number:11
Page Range:103314
Date:19 November 2021
Official Publication:http://doi.org/10.1016/j.isci.2021.103314
PubMed:View item in PubMed

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