PhD Scientific Days 2024

Poster Session M - Cardiovascular Medicine and Research 1.

Characterisation of myocardial immune checkpoint expression in advanced heart failure

Előadó neve

Dr. Tamás, Gergely

Neptun code

CQN2WF

Előadó munkahelye

Department of Pharmacology and Pharmacotherapy, Semmelweis Universeity

Előadó telefonszáma

+36209504707

Előadó e-mail címe

gergely.tamas@semmelweis.hu

Az előadás címe

Characterisation of myocardial immune checkpoint expression in advanced heart failure

Szerző(k) neve és munkahelye

Tamás Gergely¹, Zsombor Hegedűs¹, Tamás Kovács¹, Zsófia Onódi¹, Bálint András Barta², Ali Alex Sayour², Tamás Radovits², Béla Merkely², Péter Ferdinandy¹, Zoltán V. Varga¹

1: Department of Pharmacology and Pharmacotherapy, Semmelweis University
2: Heart and Vascular Center, Semmelweis University

Bemutatás módja

Poszter

Szekció

Poster Session M - Cardiovascular Medicine and Research 1.

Language of the presentation

Hungarian

Preferred session

Cardiovascular Medicine and Research

Összefoglaló szövege

Introduction: The key regulatory molecules of the adaptive immune response (co-stimulatory and co-inhibitory) are also known as immune checkpoints (ICs). These ICs are the basis of novel immunotherapies in several devastating diseases, such as cancer, graft versus host disease, or rheumatoid arthritis. Nevertheless, the side effects of ICs-targeting therapies are not fully known. Certain IC inhibitors have cardiotoxic adverse effects and cause heart failure (HF), suggesting that ICs are essential for preserving cardiac homeostasis. However, the expression patterns of immune checkpoints in the healthy and failing human heart are not currently known.
Methods and results: In this study, our goal was to characterize the expression of immunological checkpoints in patients with end-stage HF. At the time of heart transplantation, samples of myocardial tissue were obtained from patients who had heart failure with non-ischemic etiology (DCM, n=7) and ischemic etiology (IHD, n=7). Healthy organ donors whose hearts were not used for transplantation due to technical issues were our healthy controls (n=6). The level of expression of different co-inhibitory IC proteins (PD-L1, CTLA-4, LAG3, and B7-H3) in the heart was characterized via Western blot analysis in a smaller cohort. Of the investigated checkpoints, LAG3 did not show differences between DCM and control groups, while in the IHD group, LAG3 significantly increased. In the case of CTLA-4 and B7-H3, there was no significant differences between the control and HF groups. PD-L1 showed a significant increase in IHD and DCM samples compared with the control. Thus, we validated the results in the case of PD-L1 in a larger cohort of patients with end-stage HF (n=77). Myocardial PD-L1 expression showed a significant negative correlation with left ventricular ejection fraction, a marker of systolic cardiac function.
Conclusions: A negative correlation has been discovered between cardiac function and the upregulation of myocardial PD-L1 in failing hearts. In HF, PD-L1 is a promising target for both diagnosis and treatment and further investigation is required to understand its role in cardiac homeostasis.

University

Semmelweis University

Supervisor

Dr. Zoltán Varga

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

7999

Start

16:40

End

16:43