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.

SODIUM-DEPENDENT GLUCOSE TRANSPORTERS (SGLT) IN HUMAN ISCHEMIC HEART: A NEW POTENTIAL PHARMACOLOGICAL TARGET / Di Franco, Alessandra; Cantini, Giulia; Tani, Alessia; Coppini, Raffaele; Zecchi-Orlandini, Sandra; Raimondi, Laura; Luconi, Michaela; Mannucci, Edoardo. - In: INTERNATIONAL JOURNAL OF CARDIOLOGY. - ISSN 1874-1754. - STAMPA. - 243:(2017), pp. 86-90. [10.1016/j.ijcard.2017.05.032]

SODIUM-DEPENDENT GLUCOSE TRANSPORTERS (SGLT) IN HUMAN ISCHEMIC HEART: A NEW POTENTIAL PHARMACOLOGICAL TARGET

DI FRANCO, ALESSANDRA;CANTINI, GIULIA;TANI, ALESSIA;COPPINI, RAFFAELE;ZECCHI, SANDRA;RAIMONDI, LAURA;LUCONI, MICHAELA
;
MANNUCCI, EDOARDO
2017

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.
2017
243
86
90
Di Franco, Alessandra; Cantini, Giulia; Tani, Alessia; Coppini, Raffaele; Zecchi-Orlandini, Sandra; Raimondi, Laura; Luconi, Michaela; Mannucci, Edoar...espandi
File in questo prodotto:
File Dimensione Formato  
Di Franco et al Int J Card 2017.pdf

Accesso chiuso

Tipologia: Pdf editoriale (Version of record)
Licenza: Tutti i diritti riservati
Dimensione 691.47 kB
Formato Adobe PDF
691.47 kB Adobe PDF   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1081357
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 119
  • ???jsp.display-item.citation.isi??? 113
social impact