Animal care, the experimental procedures, protocols for all animal experiments were approved by the Animal Research Ethics Committee, Mie University School of Medicine (Number 2019-28). All animal experiments were carried out in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publication). Catheterization and tissue harvest were performed under anesthesia using intraperitoneal sodium pentobarbital. Echocardiography was performed under anesthesia using isoflurane. During the course of the experiment, ethical endpoints were indicated based on feeding and watering difficulties, agonizing symptoms (e.g., dyspnea, self-injurious behaviour), prolonged external abnormalities (e.g., diarrhoea, bleeding) with no signs of recovery, and rapid weight loss (> 20% in a few days). All efforts were made to minimize pain perception in the animal studies.
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