PhD Scientific Days 2020

Theoretical and Translational I. Lectures

Investigation of the Direct Cardiovascular Protective Effects of a Novel Group of Antidiabetic Agents

Előadó neve

Dr. Sayour, Alex Ali

Előadó munkahelye

Department of Cardiology, Heart and Vascular Center - Semmelweis University

Előadó telefonszáma

+36-1-4586842

Előadó e-mail címe

alexali.sayour@gmail.com

Az előadás címe

Investigation of the Direct Cardiovascular Protective Effects of a Novel Group of Antidiabetic Agents

Szerző(k) neve és munkahelye

1 Department of Cardiology, Heart and Vascular Center - Semmelweis University, Budapest

Szekció

Theoretical and Translational I. Lectures

Language of the presentation

English

Section, first choice

Theoretical and Translational Medicine

Section, second choice

Clinical Medicine

Összefoglaló szövege

Introduction: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are novel antidiabetic agents that have shown superior efficacy in preventing hospitalization for heart failure (HF) in diabetic, as well as non-diabetic patients. The latter suggests that SGLT2 inhibitors exert direct cardioprotection independently of antidiabetic action, the mechanism of which is incompletely understood but has been proposed to be partially mediated by unspecific inhibition of SGLT1.
Aims: We sought to characterize left ventricular (LV) mRNA expressions of SGLT1 and SGLT2, as well as those of the other two major glucose transporters (GLUT1 and GLUT4) in control and end-stage HF patients with various aetiologies.
Method: Control LV papillary muscles were harvested from patients undergoing mitral valve repair with otherwise no evidence of myocardial disease or LV functional alteration (Control, n=9). An overall of 44 LV myocardial samples from patients with end-stage HF undergoing heart transplantation were obtained, with the following subgroups: idiopathic dilated cardiomyopathy (DCM, n=12), ischemic heart disease with or without type 2 diabetes (IHD+T2DM, n=11; IHD, n=14) and hypertrophic cardiomyopathy (HCM, n=7). mRNA expressions were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Echocardiography-derived LV end-diastolic diameter (LVEDD) and LV ejection fraction (LVEF) were registered prior to surgery.
Results: We found no expression of SGLT2 in the myocardium. Compared to controls, patients with DCM, IHD and IHD+T2DM had a two-fold increase in LV SGLT1 mRNA expression, while in HCM patients SGLT1 expression was unchanged. LV SGLT1 expression significantly correlated with LVEDD (r=0.493, P<0.001) and LVEF (r=-0.477, P<0.001). GLUT1 was also significantly upregulated in HF patients (except in HCM) but correlated significantly only with LVEF (r=-0.326, P=0.021). GLUT4 expression was unchanged.
Conclusion: Left ventricular SGLT1 mRNA expression shows aetiology-dependent alterations in end-stage HF patients and correlates strongly with LVEDD and LVEF, indicating a possible involvement in adverse cardiac remodelling. HF patients with higher LV SGLT1 expression might derive more benefit from SGLT2 inhibitor therapy.

Additional Information

Supervisor: Tamás Radovits, MD PhD
E-mail address: radovitstamas@yahoo.com

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4603

Start

10:20

End

10:35

Authors (legacy)

1 Department of Cardiology, Heart and Vascular Center - Semmelweis University, Budapest