PhD Scientific Days 2025

Cardiovascular Medicine and Research II.

Tirzepatide Mitigates Heart Failure Progression and Enhances Survival in an Angiotensin II-driven Mouse Model

Előadó neve

Hegedűs Zsombor, MSc

Neptun code

RVZY24

Előadó munkahelye

Department of Pharmacology and Pharmacotherapy, Semmelweis University

Előadó telefonszáma

+36202609682

Előadó e-mail címe

hegedus.zsombor@semmelweis.hu

Az előadás címe

Tirzepatide Mitigates Heart Failure Progression and Enhances Survival in an Angiotensin II-driven Mouse Model

Szerző(k) neve és munkahelye

Zsombor I. Hegedűs¹, Márk E. Jakab¹, Andrea Kovács¹, Sára Antal¹, Péter Ferdinandy¹, Zoltán V. Varga¹, Viktória E. Tóth¹

1: Department of Pharmacology and Pharmacotherapy, Semmelweis University

Bemutatás módja

Szóbeli

Szekció

Cardiovascular Medicine and Research II.

Language of the presentation

English

Preferred session

Cardiovascular Medicine and Research

Összefoglaló szövege

Introduction: Recent heart failure trials show that incretin analogues used in type 2 diabetes mellitus (T2DM) and obesity, such as GLP1-receptor agonist liraglutide (Lira), reduce serious adverse cardiac events. In patients with heart failure with preserved ejection fraction (HFpEF), the dual GIP/GLP1-receptor agonist tirzepatide improved cardiovascular outcomes in the SUMMIT study. However, their role in heart failure with reduced ejection fraction (HFrEF) remains unclear. Aims: To investigate this question, we conducted a head-to-head comparison study in a mouse model of non-ischaemic cardiac damage brought on by continuous AngII infusion.
Methods: AngII-induction (1.5 mg/kg/day) was carried out with osmotic minipumps implantation subcutaneously (s.c.) to 5-month-old male Balb/c mice, or sham surgery was performed. Following this, the animals received vehicle (Veh i.p.), TZP (48 µg/day s.c.), or Lira (300 µg/day i.p.) treatment for 14 days in the following groups: Sham/Veh (n=7), AngII/Veh (n=15), Sham/Lira (n=7), AngII/Lira (n=15), Sham/TZP (n=8), AngII/TZP (n=15).
Echocardiography, electrocardiography, immunohistochemistry, and qRT-PCR were performed to characterize the structural, functional, and molecular features of the heart.
Results: The mortality rate was significantly higher in AngII/Veh animals (mortality: 60%) compared to controls, whereas TZP treatment significantly increased the chance of surviving next to AngII-infusion (mortality: 20%). Treatment with both compounds led to significant weight loss compared to controls. TZP and Lira treatment next to AngII-infusion preserved cardiac systolic and diastolic function compared with vehicle-treated animals, as shown by normal ejection fraction and E/e’, respectively. The elevation of cardiac fibrosis and hypertrophy markers, including Ctgf, Col1a1, Col3a1, and Nppa induced by AngII, was significantly reduced due to treatment with both compounds. Moreover, TZP also reduced the elevated Nppb level.
Conclusions: TZP and Lira preserved cardiac function and decreased markers of hypertrophy and fibrosis in mice with AngII-induced reduced ejection fraction heart failure, whereas TZP also significantly decreased mortality. In addition to HFpEF, the use of incretin analogues may also be of clinical relevance in the treatment of HFrEF.
Funding: Semmelweis Tudományos és Innovációs Alap Nr. 38243/IKP/2023

University

Semmelweis University

Supervisor

Zoltán V. Varga

Publication of my abstract

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

phd.section.field

in doctoral studies before complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem hagyta jóvá

Előadó

8937

Start

15:30

End

15:45