Alessandra Di Franco1, Giulia Cantini1, Alessia Tani2, Raffaele Coppini3, Sandra Zecchi-Orlandini2, Laura Raimondi3, Michaela Luconi4, Edoardo Mannucci5. 1. Endocrinology Unit, Dept. Clinical and Experimental Biomedical Sciences "Mario Serio", University of Florence, Viale G. Pieraccini, 6, Florence, Italy. 2. Section of Anatomy and Histology, Dept. Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, Florence, Italy. 3. Pharmacology Unit, Dept. of Neuroscience, Psychology, Drug Sciences and Child Health, University of Florence, Viale G. Pieraccini, 6, Florence, Italy. 4. Endocrinology Unit, Dept. Clinical and Experimental Biomedical Sciences "Mario Serio", University of Florence, Viale G. Pieraccini, 6, Florence, Italy. Electronic address: michaela.luconi@unifi.it. 5. Endocrinology Unit, Dept. Clinical and Experimental Biomedical Sciences "Mario Serio", University of Florence, Viale G. Pieraccini, 6, Florence, Italy; Diabetology, Careggi Hospital, Florence, Italy.
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.
BACKGROUND:Empagliflozin is reported to reduce cardiovascular mortality and the rate of hospitalization for heart failure in type 2 diabeticpatients 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 hypertrophichuman 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.
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