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SGLT2 Inhibitors Play a Salutary Role in Heart Failure via Modulation of the Mitochondrial Function.
Front Cardiovasc Med 2019; 6:186FC

Abstract

Three cardiovascular outcome trials of sodium glucose cotransporter 2 (SGLT2) inhibitors, including the EMPA-REG OUTCOME trial, CANVAS Program, and DECLARE TIMI 58 trial, revealed that SGLT2 inhibitors were superior to a matching placebo in reducing cardiovascular events, including mortality and hospitalization for heart failure, in patients with type 2 diabetes. However, the detailed mechanism underlying the beneficial effects that SGLT2 inhibitors exert on cardiovascular diseases remains to be elucidated. We herein review the latest findings of the salutary mechanisms of SGLT2 inhibitors in cardiomyocytes, especially focusing on their mitochondrial function-mediated beneficial effects. The administration of SGLT2 inhibitors leads to the elevation of plasma levels of ketone bodies, which are an efficient energy source in the failing heart, by promoting oxidation of the mitochondrial coenzyme Q couple and enhancing the free energy of cytosolic ATP hydrolysis. SGLT2 inhibitors also promote sodium metabolism-mediated cardioprotective effects. These compounds could reduce the intracellular sodium overload to improve mitochondrial energetics and oxidative defense in the heart through binding with NHE and/or SMIT1. Furthermore, SGLT2 inhibitors could modulate mitochondrial dynamics by regulating the fusion and fission of mitochondria. Together with ongoing large-scale clinical trials to evaluate the efficacy of SGLT2 inhibitors in patients with heart failure, intensive investigations regarding the mechanism through which SGLT2 inhibitors promote the restoration in cases of heart failure would lead to the establishment of these drugs as potent anti-heart failure drugs.

Authors+Show Affiliations

Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31970162

Citation

Maejima, Yasuhiro. "SGLT2 Inhibitors Play a Salutary Role in Heart Failure Via Modulation of the Mitochondrial Function." Frontiers in Cardiovascular Medicine, vol. 6, 2019, p. 186.
Maejima Y. SGLT2 Inhibitors Play a Salutary Role in Heart Failure via Modulation of the Mitochondrial Function. Front Cardiovasc Med. 2019;6:186.
Maejima, Y. (2019). SGLT2 Inhibitors Play a Salutary Role in Heart Failure via Modulation of the Mitochondrial Function. Frontiers in Cardiovascular Medicine, 6, p. 186. doi:10.3389/fcvm.2019.00186.
Maejima Y. SGLT2 Inhibitors Play a Salutary Role in Heart Failure Via Modulation of the Mitochondrial Function. Front Cardiovasc Med. 2019;6:186. PubMed PMID: 31970162.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SGLT2 Inhibitors Play a Salutary Role in Heart Failure via Modulation of the Mitochondrial Function. A1 - Maejima,Yasuhiro, Y1 - 2020/01/08/ PY - 2019/11/03/received PY - 2019/12/10/accepted PY - 2020/1/24/entrez PY - 2020/1/24/pubmed PY - 2020/1/24/medline KW - NHE KW - SGLT2 KW - fission KW - fusion KW - ketone body KW - mitochondria SP - 186 EP - 186 JF - Frontiers in cardiovascular medicine JO - Front Cardiovasc Med VL - 6 N2 - Three cardiovascular outcome trials of sodium glucose cotransporter 2 (SGLT2) inhibitors, including the EMPA-REG OUTCOME trial, CANVAS Program, and DECLARE TIMI 58 trial, revealed that SGLT2 inhibitors were superior to a matching placebo in reducing cardiovascular events, including mortality and hospitalization for heart failure, in patients with type 2 diabetes. However, the detailed mechanism underlying the beneficial effects that SGLT2 inhibitors exert on cardiovascular diseases remains to be elucidated. We herein review the latest findings of the salutary mechanisms of SGLT2 inhibitors in cardiomyocytes, especially focusing on their mitochondrial function-mediated beneficial effects. The administration of SGLT2 inhibitors leads to the elevation of plasma levels of ketone bodies, which are an efficient energy source in the failing heart, by promoting oxidation of the mitochondrial coenzyme Q couple and enhancing the free energy of cytosolic ATP hydrolysis. SGLT2 inhibitors also promote sodium metabolism-mediated cardioprotective effects. These compounds could reduce the intracellular sodium overload to improve mitochondrial energetics and oxidative defense in the heart through binding with NHE and/or SMIT1. Furthermore, SGLT2 inhibitors could modulate mitochondrial dynamics by regulating the fusion and fission of mitochondria. Together with ongoing large-scale clinical trials to evaluate the efficacy of SGLT2 inhibitors in patients with heart failure, intensive investigations regarding the mechanism through which SGLT2 inhibitors promote the restoration in cases of heart failure would lead to the establishment of these drugs as potent anti-heart failure drugs. SN - 2297-055X UR - https://www.unboundmedicine.com/medline/citation/31970162/SGLT2_Inhibitors_Play_a_Salutary_Role_in_Heart_Failure_via_Modulation_of_the_Mitochondrial_Function L2 - https://doi.org/10.3389/fcvm.2019.00186 DB - PRIME DP - Unbound Medicine ER -
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