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KMID : 0368120210510030251
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Korean Circulation Journal
2021 Volume.51 No. 3 p.251 ~ p.262
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Sodium/glucose Co-Transporter 2 Inhibitor, Empagliflozin, Alleviated Transient Expression of SGLT2 after Myocardial Infarction
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Lee Soo-Yong
Lee Tae-Wook
Park Gyu-Tae
Kim Jae-Ho
Lee Hyun-Chae
Han Jung-Hwa
Yoon Ae-Seon
Yoon Da-Hye
Kim Shuk-Mann
Jung Soon-Myung
Choi Jin-Hee
Chon Min-Ku
Lee Sang-Hyun
Hwang Ki-Won
Kim Jeong-Su
Park Yong-Hyun
Kim June-Hong
Chun Kook-Jin
Hur Jin
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Abstract
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Background and Objectives: Large clinical studies of sodium/glucose cotransporter 2 (SGLT2) inhibitors have shown a significant beneficial effect on heart failure-associated hospitalization and cardiovascular events. As SGLT2 is known to be absent in heart cells, improved cardiovascular outcomes are thought to be accounted for by the indirect effects of the drug. We sought to confirm whether such benefits were mediated through SGLT2 expressed in the heart using myocardial infarction (MI) model.
Methods: Mice pre-treated with empagliflozin (EMPA), an SGLT2 inhibitor, showed a significantly reduced infarct size compared with the vehicle group three days post-MI. Interestingly, we confirmed SGLT2 localized in the infarct zone. The sequential changes of SGLT2 expression after MI were also evaluated.
Results: One day after MI, SGLT2 transiently appeared in the ischemic areas in the vehicle group and increased until 72 hours. The appearance of SGLT2 was delayed and less in amount compared with the vehicle group. Additionally, there was a significant difference in metabolites, including glucose and amino acids in the 1H nuclear magnetic resonance analysis between groups.
Conclusions: Our work demonstrates that SGLT2 is transiently expressed in heart tissue early after MI and EMPA may directly operate on SGLT2 to facilitate metabolic substrates shifts.
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KEYWORD
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Myocardial infarction, Sodium-glucose transporter 2, Sodium-glucose transporter 2 inhibitors, Metabolism
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