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Sodium/glucose Co-Transporter 2 Inhibitor, Empagliflozin, Alleviated Transient Expression of SGLT2 after Myocardial Infarction

Korean Circulation Journal 2021년 51권 3호 p.251 ~ 262
이수용, 이태욱, 박규태, 김재호, 이현채, 한정화, 윤애선, 윤다혜, 김석만, 정순명, 최진희, Chon Min-Ku, 이상현, 황기원, 김정수, 박용현, 김준홍, 전국진, 허진,
소속 상세정보
이수용 ( Lee Soo-Yong ) - Pusan National University Yangsan Hospital Department of Internal Medicine
이태욱 ( Lee Tae-Wook ) - Pusan National University School of Medicine Department of Physiology
박규태 ( Park Gyu-Tae ) - Pusan National University School of Medicine Department of Physiology
김재호 ( Kim Jae-Ho ) - Pusan National University School of Medicine Department of Physiology
이현채 ( Lee Hyun-Chae ) - Pusan National University School of Medicine Department of Convergence Medicine
한정화 ( Han Jung-Hwa ) - Pusan National University School of Medicine Department of Convergence Medicine
윤애선 ( Yoon Ae-Seon ) - Pusan National University School of Medicine Department of Convergence Medicine
윤다혜 ( Yoon Da-Hye ) - Pusan National University Department of Chemistry
김석만 ( Kim Shuk-Mann ) - Pusan National University Department of Chemistry
정순명 ( Jung Soon-Myung ) - Pusan National University Yangsan Hospital Department of Internal Medicine
최진희 ( Choi Jin-Hee ) - Pusan National University Yangsan Hospital Department of Internal Medicine
 ( Chon Min-Ku ) - Pusan National University Yangsan Hospital Department of Internal Medicine
이상현 ( Lee Sang-Hyun ) - Pusan National University Yangsan Hospital Department of Internal Medicine
황기원 ( Hwang Ki-Won ) - Pusan National University Yangsan Hospital Department of Internal Medicine
김정수 ( Kim Jeong-Su ) - Pusan National University Yangsan Hospital Department of Internal Medicine
박용현 ( Park Yong-Hyun ) - Pusan National University Yangsan Hospital Department of Internal Medicine
김준홍 ( Kim June-Hong ) - Pusan National University Yangsan Hospital Department of Internal Medicine
전국진 ( Chun Kook-Jin ) - Pusan National University Yangsan Hospital Department of Internal Medicine
허진 ( Hur Jin ) - Pusan National University School of Medicine Department of Convergence Medicine

Abstract


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.

키워드

Myocardial infarction; Sodium-glucose transporter 2; Sodium-glucose transporter 2 inhibitors; Metabolism

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