Sodium-dependent glucose transporters (SGLT) in human ischemic heart: A new potential pharmacological target. (15th September 2017)

• Record Type: Journal Article
• Authors: Di Franco, Alessandra; Cantini, Giulia; Tani, Alessia; Coppini, Raffaele; Zecchi-Orlandini, Sandra; Raimondi, Laura; Luconi, Michaela; Mannucci, Edoardo
• Is Part Of: International journal of cardiology. Volume 243(2017)
• Page Start: 86
• Page End: 90
• Publication Date: 2017-09-15
• Subjects: Ischemic heart disease -- Myocardial disease -- Cardiac hypertrophy -- Heart failure -- Empagliflozin -- SGLT1 -- SGLT2; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2017.05.032
• Languages: English
• ISSNs: 0167-5273

Abstract

Abstract: Background: Empagliflozin is reported to reduce cardiovascular mortality and the rate of hospitalization for heart failure in type 2 diabetic patients with prior cardiovascular events. The mechanisms underlying the cardiac effects of this sodium/glucose transporter 2 (SGT2) inhibitor have not yet been clarified, though a direct action of the drug on the cardiomyocytes could be hypothesized. The aim of the present study is to assess the relative expression of SGLT2 and SGLT1, the two most relevant members of the SGLT family being potentially responsive to empagliflozin, in normal, ischemic and hypertrophic human hearts. Methods: Tissue biopsies of healthy ( n = 9), ischemic ( n = 9) and hypertrophic ( n = 6) human hearts were analyzed by real time quantitative RT-PCR, confocal immunofluorescence and Western blot techniques. Results: We found no expression of SGLT2 in either normal or pathological conditions, whereas SGLT1 was expressed in normal myocardial tissue and significantly upregulated in ischemia and hypertrophy, in association with increased phosphorylation in activating domains of the intracellular second messengers AMP-activated protein kinase (AMPK), extracellular-signal regulated kinase 1 and 2 (ERK-1/2) and mammalian target of rapamycin (mTOR). Conclusions: These findings open the possibility that hyperexpressed SGLT1 in cardiomyocytes may represent a potential pharmacological target for cardioprotection. Highlights: SGLT2 is not present in human hearts either in normoxic and ischemic/hypertrophic conditions. SGLT1 increases in human hearts in ischemic/hypertrophic conditions. Empagliflozin may act through SGLT1 inhibition in human hearts in hypoxic conditions.