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• W2953560887 abstract "Mitochondrial dysfunction plays a role in the progression of cardiovascular diseases including heart failure. 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins), which inhibit ROS synthesis, show cardioprotective effects in chronic heart failure. However, the beneficial role of statins in mitochondrial protection in heart failure remains unclear.Rats were treated with angiotensin II (1.5 mg·kg-1 ·day-1 ) or co-administered simvastatin (oral, 10 mg·kg-1 ) for 14 days; and then administration was stopped for the following 14 days. Cardiac structure/function was examined by wheat germ agglutinin staining and echocardiography. Mitochondrial morphology and the numbers of lipid droplets, lysosomes, autophagosomes, and mitophagosomes were determined by transmission electron microscopy. Human cardiomyocytes were stimulated, and intracellular ROS and mitochondrial membrane potential (ΔΨm ) changes were measured by flow cytometry and JC-1 staining, respectively. Autophagy and mitophagy-related and mitochondria-regulated apoptotic proteins were identified by immunohistochemistry and western blotting.Simvastatin significantly reduced ROS production and attenuated the disruption of ΔΨm . Simvastatin induced the accumulation of lipid droplets to provide energy for maintaining mitochondrial function, promoted autophagy and mitophagy, and inhibited mitochondria-mediated apoptosis. These findings suggest that mitochondrial protection mediated by simvastatin plays a therapeutic role in heart failure prevention by modulating antioxidant status and promoting energy supplies for autophagy and mitophagy to inhibit mitochondrial damage and cardiomyocyte apoptosis.Mitochondria play a key role in mediating heart failure progression. Simvastatin attenuated heart failure, induced by angiotensin II, via mitochondrial protection and might provide a new therapy to prevent heart failure." @default.
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• W2953560887 date "2019-08-24" @default.
• W2953560887 modified "2023-10-14" @default.
• W2953560887 title "Mitochondrial protection by simvastatin against angiotensin II‐mediated heart failure" @default.
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• W2953560887 doi "https://doi.org/10.1111/bph.14781" @default.
• W2953560887 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6780047" @default.
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