SGLT2 Inhibitor, Canagliflozin, Attenuates Myocardial Infarction in the Diabetic and Nondiabetic Heart

Autor: Ven G. Lim, MBChB, Robert M. Bell, PhD, Sapna Arjun, PhD, Maria Kolatsi-Joannou, PhD, David A. Long, PhD, Derek M. Yellon, PhD, DSc
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: JACC: Basic to Translational Science, Vol 4, Iss 1, Pp 15-26 (2019)
Druh dokumentu: article
ISSN: 2452-302X
DOI: 10.1016/j.jacbts.2018.10.002
Popis: Summary: The authors hypothesized that despite similar cardiovascular event rates, the improved cardiovascular survival from sodium glucose transporter 2 (SGLT2) inhibition, seen clinically, could be via a direct cytoprotective effect, including protection against myocardial ischemia/reperfusion injury. Langendorff-perfused hearts, from diabetic and nondiabetic rats, fed long-term for 4 weeks with canagliflozin, had lower infarct sizes; this being the first demonstration of canagliflozin’s cardioprotective effect against ischemia/reperfusion injury in both diabetic and nondiabetic animals. By contrast, direct treatment of isolated nondiabetic rat hearts with canagliflozin, solubilized in the isolated Langendorff perfusion buffer, had no impact on infarct size. This latter study demonstrates that the infarct-sparing effect of long-term treatment with canagliflozin results from either a glucose-independent effect or up-regulation of cardiac prosurvival pathways. These results further suggest that SGLT2 inhibitors could be repurposed as novel cardioprotective interventions in high-risk cardiovascular patients irrespective of diabetic status. Key Words: cardioprotection, diabetes, ischemia-reperfusion injury, myocardial infarction, SGLT2 inhibitor
Databáze: Directory of Open Access Journals