Depletion of cardiac cardiolipin synthase alters systolic and diastolic function

• DOI: 10.1016/j.isci.2021.103314
• Publication Date: 2021-10-22T08:29:03Z
• Authors: 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
• Keywords: CLs upper limits

Cardiolipin (CL) is a major cardiac mitochondrial phospholipid maintaining regular morphology and function in cardiomyocytes. Cardiac CL production includes its biosynthesis remodeling process. Here we studied the impact of enzyme cardiolipin synthase (CLS) on function. CLS species were significantly downregulated cardiomyocytes following catecholamine-induced damage mice, accompanied by increased oxygen consumption rates, signs oxidative stress, uncoupling. RNAi-mediated cardiomyocyte-specific knockdown Drosophila melanogaster resulted marked dilatation, severe impairment systolic performance, slower diastolic filling velocity assessed fluorescence-based heart imaging. Finally, showed that CL72:8 decreased samples from patients with failure reduced ejection fraction (HFrEF). In summary, identified as regulator Considering depletion HFrEF, pharmacological targeting may be promising therapeutic approach.