| Title: | Empagliflozin suppresses mitochondrial reactive oxygen species generation and mitigates the inducibility of atrial fibrillation in diabetic rats |
| Authors: | Koizumi, Takuya Browse this author |
| Watanabe, Masaya Browse this author →KAKEN DB |
| Yokota, Takashi Browse this author |
| Tsuda, Masumi Browse this author |
| Handa, Haruka Browse this author |
| Koya, Jiro Browse this author |
| Nishino, Kotaro Browse this author |
| Tatsuta, Daishiro Browse this author |
| Natsui, Hiroyuki Browse this author |
| Kadosaka, Takahide Browse this author |
| Koya, Taro Browse this author |
| Nakao, Motoki Browse this author |
| Hagiwara, Hikaru Browse this author |
| Kamada, Rui Browse this author |
| Temma, Taro Browse this author |
| Tanaka, Shinya Browse this author |
| Anzai, Toshihisa Browse this author →KAKEN DB |
| Keywords: | empagliflozin |
| diabetes |
| mitochondria |
| reactive oxygen species |
| SGLT2 inhibitor |
| Issue Date: | 6-Feb-2023 |
| Publisher: | Frontiers Media |
| Journal Title: | Frontiers in Cardiovascular Medicine |
| Volume: | 10 |
| Start Page: | 1005408 |
| Publisher DOI: | 10.3389/fcvm.2023.1005408 |
| Abstract: | IntroductionRecent studies have demonstrated that sodium-glucose co-transporter-2 inhibitors (SGLT2-i) reduce the risk of atrial fibrillation (AF) in patients with diabetes mellitus (DM), in which oxidative stress due to increased reactive oxygen species (ROS) contributes to the pathogenesis of AF. We aimed to further investigate this, and examine whether the SGLT2-i empagliflozin suppresses mitochondrial-ROS generation and mitigates fibrosis. MethodsA high-fat diet and low-dose streptozotocin treatment were used to induce type-2 DM (T2DM) in Sprague-Dawley rats. The rats were randomly divided into three groups: control, DM, and DM treated with empagliflozin (30 mg/kg/day) for 8 weeks. The mitochondrial respiratory capacity and ROS generation in the atrial myocardium were measured using a high-resolution respirometer. Oxidative stress markers and protein expression related to mitochondrial biogenesis and dynamics as well as the mitochondrial morphology were examined in the atrial tissue. Additionally, mitochondrial function was examined in H9c2 cardiomyoblasts. Atrial tachyarrhythmia (ATA) inducibility, interatrial conduction time (IACT), and fibrosis were also measured. ResultsInducibility of ATA, fibrosis, and IACT were increased in rats with DM when compared to controls, all of which were restored by empagliflozin treatment. In addition, the rats with DM had increased mitochondrial-ROS with an impaired complex I-linked oxidative phosphorylation capacity. Importantly, empagliflozin seemed to ameliorate these impairments in mitochondrial function. Furthermore, empagliflozin reversed the decrease in phosphorylated AMPK expression and altered protein levels related to mitochondrial biogenesis and dynamics, and increased mitochondrial content. Empagliflozin also improved mitochondrial function in H9c2 cells cultured with high glucose medium. DiscussionThese data suggest that empagliflozin has a cardioprotective effect, at least in part, by reducing mitochondrial ROS generation through AMPK signaling pathways in the atrium of diabetic rats. This suggests that empagliflozin might suppress the development of AF in T2DM. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/88932 |
| Appears in Collections: | 北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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