Zitieren Sie bitte immer diesen URN: urn:nbn:de:kobv:b43-536833
Depletion of Cardiac Cardiolipin Synthase Alters Systolic and Diastolic Function
- 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 aCardiolipin (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…
Autor*innen: | E. Smeir, S. Leberer, A. Blumrich, G. Vogler, A. Vasiliades, S. Dresen, Carsten JaegerORCiD, Y. Gloaguen, C. Klose, D. Beule, P. Schulze, R. Bodmer, A. Foryst-Ludwig, U. Kintscher |
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Dokumenttyp: | Zeitschriftenartikel |
Veröffentlichungsform: | Verlagsliteratur |
Sprache: | Englisch |
Titel des übergeordneten Werkes (Englisch): | iScience |
Jahr der Erstveröffentlichung: | 2021 |
Organisationseinheit der BAM: | 1 Analytische Chemie; Referenzmaterialien |
1 Analytische Chemie; Referenzmaterialien / 1.8 Umweltanalytik | |
Veröffentlichende Institution: | Bundesanstalt für Materialforschung und -prüfung (BAM) |
Verlag: | Cell Press |
Jahrgang/Band: | 24 |
Ausgabe/Heft: | 11 |
Erste Seite: | 103314 |
DDC-Klassifikation: | Naturwissenschaften und Mathematik / Chemie / Analytische Chemie |
Freie Schlagwörter: | Cardiolipins; Heart failure; High-resolution mass spectrometry; Lipidomics; Nontarget analysis |
Themenfelder/Aktivitätsfelder der BAM: | Chemie und Prozesstechnik |
Chemie und Prozesstechnik / Chemische Charakterisierung und Spurenanalytik | |
DOI: | 10.1016/j.isci.2021.103314 |
URN: | urn:nbn:de:kobv:b43-536833 |
Verfügbarkeit des Dokuments: | Datei für die Öffentlichkeit verfügbar ("Open Access") |
Lizenz (Deutsch): | Creative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International |
Datum der Freischaltung: | 03.11.2021 |
Referierte Publikation: | Ja |
Datum der Eintragung als referierte Publikation: | 29.11.2021 |
Schriftenreihen ohne Nummerierung: | Wissenschaftliche Artikel der BAM |