Depletion of cardiac cardiolipin synthase alters systolic and diastolic function

Summary: 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 s...

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Autores principales:	Elia Smeir, Sarah Leberer, Annelie Blumrich, Georg Vogler, Anastasia Vasiliades, Sandra Dresen, Carsten Jaeger, Yoann Gloaguen, Christian Klose, Dieter Beule, P. Christian Schulze, Rolf Bodmer, Anna Foryst-Ludwig, Ulrich Kintscher
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Animal physiology Molecular physiology Molecular biology Lipidomics Science Q
Acceso en línea:	https://doaj.org/article/495faf1d987c41ec8b93ea96ff9681f2
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spelling	oai:doaj.org-article:495faf1d987c41ec8b93ea96ff9681f22021-11-20T05:09:50ZDepletion of cardiac cardiolipin synthase alters systolic and diastolic function2589-004210.1016/j.isci.2021.103314https://doaj.org/article/495faf1d987c41ec8b93ea96ff9681f22021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012839https://doaj.org/toc/2589-0042Summary: 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.Elia SmeirSarah LebererAnnelie BlumrichGeorg VoglerAnastasia VasiliadesSandra DresenCarsten JaegerYoann GloaguenChristian KloseDieter BeuleP. Christian SchulzeRolf BodmerAnna Foryst-LudwigUlrich KintscherElsevierarticleAnimal physiologyMolecular physiologyMolecular biologyLipidomicsScienceQENiScience, Vol 24, Iss 11, Pp 103314- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Animal physiology Molecular physiology Molecular biology Lipidomics Science Q
spellingShingle	Animal physiology Molecular physiology Molecular biology Lipidomics Science Q Elia Smeir Sarah Leberer Annelie Blumrich Georg Vogler Anastasia Vasiliades Sandra Dresen Carsten Jaeger Yoann Gloaguen Christian Klose Dieter Beule P. Christian Schulze Rolf Bodmer Anna Foryst-Ludwig Ulrich Kintscher Depletion of cardiac cardiolipin synthase alters systolic and diastolic function
description	Summary: 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.
format	article
author	Elia Smeir Sarah Leberer Annelie Blumrich Georg Vogler Anastasia Vasiliades Sandra Dresen Carsten Jaeger Yoann Gloaguen Christian Klose Dieter Beule P. Christian Schulze Rolf Bodmer Anna Foryst-Ludwig Ulrich Kintscher
author_facet	Elia Smeir Sarah Leberer Annelie Blumrich Georg Vogler Anastasia Vasiliades Sandra Dresen Carsten Jaeger Yoann Gloaguen Christian Klose Dieter Beule P. Christian Schulze Rolf Bodmer Anna Foryst-Ludwig Ulrich Kintscher
author_sort	Elia Smeir
title	Depletion of cardiac cardiolipin synthase alters systolic and diastolic function
title_short	Depletion of cardiac cardiolipin synthase alters systolic and diastolic function
title_full	Depletion of cardiac cardiolipin synthase alters systolic and diastolic function
title_fullStr	Depletion of cardiac cardiolipin synthase alters systolic and diastolic function
title_full_unstemmed	Depletion of cardiac cardiolipin synthase alters systolic and diastolic function
title_sort	depletion of cardiac cardiolipin synthase alters systolic and diastolic function
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/495faf1d987c41ec8b93ea96ff9681f2
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Depletion of cardiac cardiolipin synthase alters systolic and diastolic function

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