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- W4377015437 abstract "Studies of autophagy in ARVC are quite rare. Even autophagy had the opposite effects in desmin-related cardiomyopathy and dilated cardiomyopathy. This study aimed to explore the regulatory role of autophagy in the progression of ARVC. The ARVC cardiomyocytes (HL-1/shJup) were treated with autophagy activator (rapamycin) and inhibitor (chloroquine) to manipulate autophagy activity. Western blotting and immunofluorescence determined the changes of disease progression and signaling pathways. Then, autophagy was manipulated in cardiac tissue-specific Jup knockout mice to confirm the cell-derived findings. The autophagy activity of HL-1/shJup cell line was higher than that of control cells. In HL-1/shJup cells, the upstream signaling pathway of autophagy was active. During rapamycin treatment, the proteins related to lipogenesis and fibrogenesis in HL-1/shJup cells were reduced. In contrast, chloroquine treatment had the opposite effect. Moreover, rapamycin decreased and chloroquine increased intracellular oil droplet accumulation in HL-1/shJup cells. In addition, there was no significant change in Wnt/Hippo signaling pathways in cardiomyocytes after rapamycin treatment. Instead, the protein expression of the transcription factor SREBP1 that regulates lipogenesis and lysyl oxidase (LOX) that promotes fibrosis were related to the regulatory mechanism of autophagy. In ARVC mice, activated/inhibited autophagy also reduced/increased RV distance, arrhythmia, and lipogenesis through SREBP1, but not in wild-type mice. Autophagy plays a protective role in ARVC by regulating lipogenesis to attenuate disease progression. Based on this study, autophagy activators may be used in combination with existing drugs in patients with ARVC disease in the future to provide additional protection for early heart failure or heart transplantation." @default.
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- W4377015437 date "2023-05-01" @default.
- W4377015437 modified "2023-10-01" @default.
- W4377015437 title "PO-01-147 ACTIVATION OF AUTOPHAGY ATTENUATES PROGRESSION OF ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY" @default.
- W4377015437 doi "https://doi.org/10.1016/j.hrthm.2023.03.495" @default.
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