KMID : 0368120190490121183
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Korean Circulation Journal 2019 Volume.49 No. 12 p.1183 ~ p.1195
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Cardioprotective Potential of an SGLT2 Inhibitor Against Doxorubicin-Induced Heart Failure
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Oh Chang-Myung
Cho Sung-Soo Jang Ji-Yong Kim Hyeong-Seok Chun Su-Kyung Choi Min-Kyung Park Sang-Kyu Ko Young-Guk
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Abstract
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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 (¥âOHB), 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 ¥âOHB 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.
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KEYWORD
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Heart failure, Doxycycline, Sodium-Glucose Transporter 2 Inhibitors
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