Characterization of left ventricular myocardial sodium-glucose cotransporter 1 expression in patients with end-stage heart failure

• Published in: Cardiovascular diabetology 2020-09, Vol.19 (1), p.159-159, Article 159
• Main Authors: Sayour, Alex Ali, Oláh, Attila, Ruppert, Mihály, Barta, Bálint András, Horváth, Eszter Mária, Benke, Kálmán, Pólos, Miklós, Hartyánszky, István, Merkely, Béla, Radovits, Tamás
• Format: Article
• Language: English
• Subjects: Adult; Aged; AMP; AMP-activated protein kinase; AMP-Activated Protein Kinases - analysis; Atherosclerosis; Biobanks; Cardiac resynchronization therapy; Cardiomyocytes; Cardiomyopathy; Cardiovascular disease; Case-Control Studies; Clinical trials; Comorbidity; Congestive heart failure; Cooling; Coronary artery disease; Diabetes mellitus (non-insulin dependent); Dilated cardiomyopathy; Dual SGLT1/2 inhibitors; Ejection fraction; Etiology; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - analysis; Female; Gene expression; Gene Expression Regulation; Glucose; Glucose Transporter Type 1 - analysis; Glucose Transporter Type 4 - analysis; GLUT4 gene; Heart failure; Heart Failure - genetics; Heart Failure - metabolism; Heart Failure - physiopathology; Heart Failure - therapy; Heart transplantation; Humans; Hypertension; Ischemia; Laboratories; Male; Middle Aged; Mitral valve; mRNA; Myocardium - chemistry; Na+/glucose cotransporter; Original Investigation; Phosphorylation; Polymerase chain reaction; Rheumatic heart disease; SGLT2 inhibitor; Small intestine; Sodium-glucose cotransporter 1; Sodium-Glucose Transporter 1 - analysis; Sodium-Glucose Transporter 1 - genetics; Sodium-Glucose Transporter 2 - analysis; Ventricle; Western blotting
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/s12933-020-01141-1

Whereas selective sodium-glucose cotransporter 2 (SGLT2) inhibitors consistently showed cardiovascular protective effects in large outcome trials independent of the presence of type 2 diabetes mellitus (T2DM), the cardiovascular effects of dual SGLT1/2 inhibitors remain to be elucidated. Despite its clinical relevance, data are scarce regarding left ventricular (LV) SGLT1 expression in distinct heart failure (HF) pathologies. We aimed to characterize LV SGLT1 expression in human patients with end-stage HF, in context of the other two major glucose transporters: GLUT1 and GLUT4. Control LV samples (Control, n = 9) were harvested from patients with preserved LV systolic function who went through mitral valve replacement. LV samples from HF patients undergoing heart transplantation (n = 71) were obtained according to the following etiological subgroups: hypertrophic cardiomyopathy (HCM, n = 7); idiopathic dilated cardiomyopathy (DCM, n = 12); ischemic heart disease without T2DM (IHD, n = 14), IHD with T2DM (IHD + T2DM, n = 11); and HF patients with cardiac resynchronization therapy (DCM:CRT, n = 9, IHD:CRT, n = 9 and IHD-T2DM:CRT, n = 9). We measured LV SGLT1, GLUT1 and GLUT4 gene expressions with qRT-PCR. The protein expression of SGLT1, and activating phosphorylation of AMP-activated protein kinase (AMPKα) and extracellular signal-regulated kinase 1/2 (ERK1/2) were quantified by western blotting. Immunohistochemical staining of SGLT1 was performed. Compared with controls, LV SGLT1 mRNA and protein expressions were significantly and comparably upregulated in HF patients with DCM, IHD and IHD + T2DM (all P