PhD Scientific Days 2022

Translational Medicine I. (Poster discussion will take place on the terrace of the room during the Coffee Break)

Left ventricular SGLT1 expression is upregulated in heart failure in humans and rat model

Előadó neve

Dr. Sayour, Alex Ali

Előadó munkahelye

Heart and Vascular Center, Semmelweis University, Budapest

Előadó telefonszáma

208258126

Előadó e-mail címe

alexali.sayour@gmail.com

Az előadás címe

Left ventricular SGLT1 expression is upregulated in heart failure in humans and rat model

Szerző(k) neve és munkahelye

Alex Ali Sayour1, Mihály Ruppert1, Attila Oláh1, Bálint András Barta1, István Hartyánszky1, Béla Merkely1, Tamás Radovits1

1 Heart and Vascular Center, Semmelweis University, Budapest

Bemutatás módja

Poszter

Szekció

Translational Medicine I. (Poster discussion will take place on the terrace of the room during the Coffee Break)

Language of the presentation

Hungarian

Preferred session

Theoretical and Translational Medicine

Összefoglaló szövege

Introduction: Myocardial sodium-glucose cotransporter 1 (SGLT1) has been shown to contribute to cardiac pathological processes, whereas humans with functionally limited SGLT1 are at lower risk of developing heart failure (HF). The novel HF medications, SGLT2 inhibitors, non-selectively inhibit SGLT1 to different extent, therefore, characterization of its expression in disease conditions is relevant.
Purpose: To investigate left ventricular (LV) SGLT1 expression in humans with end-stage HF, and in a rat model of HF.
Methods: Myocardial LV samples were harvested from control subjects (Controls, n=9) undergoing valve surgery, and from patients with end-stage dilated cardiomyopathy (DCM, n=12) undergoing heart transplantation. The rat model of aorto-caval fistula (ACF, n=12) was used to induce HF with predominant LV dilation in rats during a course of 24 weeks; sham-operated animals served as controls (Sham-A, n=12). Echocardiography was used to assess LV structure and function prior to surgery in humans, as well as in rats at the end of the follow-up period. Western blotting was performed to characterize LV SGLT1 protein expression and investigate the activity of the master regulators AMPK and ERK1/2. The extent of LV nitro-oxidative stress was quantified by immunohistochemistry (3-nitrotyrosine) in rats with HF.
Results: Both humans with DCM and rats with ACF-induced HF presented with severely dilated LVs compared to respective controls, whereas LV SGLT1 protein expression was significantly upregulated similarly by ~1.7-fold in both cases (both P<0.01). These increases in SGLT1 expressions were accompanied by significant reductions in ERK1/2 activating phosphorylation (both P<0.05), whereas those of AMPK were unaffected in both cases. In rats with HF, LV SGLT1 expression correlated significantly with the extent of myocardial nitro-oxidative stress (r=0.762, P=0.037).
Conclusions: LV SGLT1 expression is upregulated in HF in both humans and small animals, and ERK1/2 shows a concomitantly reduced activity. LV SGLT1 expression correlates with the extent of nitro-oxidative stress, suggesting a possible pathological role in HF.

University and Doctoral School

Semmelweis University, Doctoral School of Theoretical and Translational Medicine

Supervisor

Tamás Radovits, MD PhD

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4603

Start

11:25

End

11:30

Authors (legacy)

Alex Ali Sayour1, Mihály Ruppert1, Attila Oláh1, Bálint András Barta1, István Hartyánszky1, Béla Merkely1, Tamás Radovits1

1 Heart and Vascular Center, Semmelweis University, Budapest