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Cardioprotective Potential of an SGLT2 Inhibitor Against Doxorubicin-Induced Heart Failure

Authors
 Chang-Myung Oh  ;  Sungsoo Cho  ;  Ji-Yong Jang  ;  Hyeongseok Kim  ;  Sukyung Chun  ;  Minkyung Choi  ;  Sangkyu Park  ;  Young-Guk Ko 
Citation
 KOREAN CIRCULATION JOURNAL, Vol.49(12) : 1183-1195, 2019 
Journal Title
 KOREAN CIRCULATION JOURNAL 
ISSN
 1738-5520 
Issue Date
2019
Keywords
Doxycycline ; Heart failure ; Sodium-Glucose Transporter 2 Inhibitors
Abstract
BACKGROUND AND OBJECTIVES: Recent studies have shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of heart failure (HF)-associated hospitalization and mortality in patients with diabetes. However, it is not clear whether SGLT2 inhibitors have a cardiovascular benefit in patients without diabetes. We aimed to determine whether empagliflozin (EMPA), an SGLT2 inhibitor, has a protective role in HF without diabetes. METHODS: Cardiomyopathy was induced in C57BL/6J mice using intraperitoneal injection of doxorubicin (Dox). Mice with HF were fed a normal chow diet (NCD) or an NCD containing 0.03% EMPA. Then we analyzed their phenotypes and performed in vitro experiments to reveal underlying mechanisms of the EMPA's effects. RESULTS: Mice fed NCD with EMPA showed improved heart function and reduced fibrosis. In vitro studies showed similar results. Phloridzin, a non-specific SGLT inhibitor, did not show any protective effect against Dox toxicity in H9C2 cells. SGLT2 inhibitor can cause increase in blood ketone levels. Beta hydroxybutyrate (βOHB), which is well known ketone body associated with SGLT2 inhibitor, showed a protective effect against Dox in H9C2 cells and in Dox-treated mice. These results suggest elevating βOHB might be a convincing mechanism for the protective effects of SGLT2 inhibitor. CONCLUSIONS: SGLT2 inhibitors have a protective effect in Dox-induced HF in mice. This implied that SGLT2 inhibitor therapy could be a good treatment strategy even in HF patients without diabetes.
Files in This Item:
T201904995.pdf Download
DOI
10.4070/kcj.2019.0180
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Ko, Young Guk(고영국) ORCID logo https://orcid.org/0000-0001-7748-5788
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/174594
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