TY - JOUR A1 - Smeir, E. A1 - Leberer, S. A1 - Blumrich, A. A1 - Vogler, G. A1 - Vasiliades, A. A1 - Dresen, S. A1 - Jaeger, Carsten A1 - Gloaguen, Y. A1 - Klose, C. A1 - Beule, D. A1 - Schulze, P. A1 - Bodmer, R. A1 - Foryst-Ludwig, A. A1 - Kintscher, U. T1 - Depletion of Cardiac Cardiolipin Synthase Alters Systolic and Diastolic Function N2 - Cardiolipin (CL) is a major cardiac mitochondrial phospholipid maintaining regular mitochondrial morphology and function in cardiomyocytes. Cardiac CL production includes ist 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.zeige mehrzeige weniger KW - High-resolution mass spectrometry KW - Nontarget analysis KW - Heart failure KW - Cardiolipins KW - Lipidomics PY - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:b43-536833 VL - 24 IS - 11 SP - 103314 PB - Cell Press AN - OPUS4-53683 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -