PhD Scientific Days 2026

Poster Session 1.F - Pharmaceutical Sciences and Health Technologies

Effects of Bempedoic Acid on Cardiomyocytes and Cardiac Omics Profiles

Name of the presenter

Nagy, Regina Norma

Institute/workplace of the presenter

Department of Pharmacology and Pharmacotherapy, Semmelweis University

Authors

Regina Norma Nagy¹, Or Fisher¹, Boglárka Frankó¹, Tamás G Gergely¹, Bennet Y Weber¹, Csenger Kovácsházi¹, Barnabás Váradi¹, Bence Ágg¹, Zoltán Giricz¹, Péter Ferdinandy¹, Anikó Görbe¹
1: Department of Pharmacology and Pharmacotherapy, Semmelweis University

Text of the abstract

Introduction
Lipid-lowering agents like statins offer cardioprotection but carry risks of hidden cardiotoxic effects. Bempedoic acid (BA), a novel therapeutic, previously showed no hidden cardiotoxicity or protection in a rat myocardial infarction model, though it modestly reduced arrhythmias. However, BA’s direct effects on cardiomyocytes and the cardiac molecular mechanisms remain unexplored.
Aims
We investigated the direct impact of BA on cardiomyocyte viability during simulated ischemia/reperfusion (I/R) and characterized the transcriptomic and proteomic shifts in the left ventricle (LV), liver, and adipose tissue following chronic treatment.
Methods
Human AC16 cardiomyocytes were treated with BA (3-100 µM) or vehicle for 1h, followed by 16h simulated ischemia (1% O2) and 2h reperfusion. In vivo, male Wistar rats received 30 mg/kg/day BA or vehicle for 28 days. Subgroups underwent 30 min of LAD occlusion and 120 min reperfusion or sham surgery. Tissues were analyzed via RNA sequencing, proteomics, and phosphoproteomics.
Results
30 and 100 µM BA significantly reduced AC16 viability under normoxia (to 59% and 22%, respectively) and exacerbated cell death during simulated ischemia (reducing viability to 20% and 12%). In vivo, BA treatment in sham rats differentially expressed 63 LV genes (four confirmed by proteomics) and induced dephosphorylation of seven LV proteins. Following I/R, only three LV genes were altered. Conversely, BA significantly modulated the liver transcriptome (432 genes), primarily affecting lipid and cholesterol metabolism, while 30 genes were altered in adipose tissue.
Conclusion
While high-dose BA showed direct toxicity in AC16 cells, in vivo results indicate it does not induce hidden cardiotoxicity during I/R. Its primary molecular effects are localized to the liver, consistent with its systemic lipid-lowering mechanism, with minimal impact on the cardiac transcriptome.
Funding
The project was supported by grants from the National Research, Development and Innovation Office (NKFIH) of Hungary (K139237 to AG). Project no. RRF-2.3.1-21-2022-00003 has been implemented with the support provided by the European Union. This project was supported by the 2025-2.1.1-EKÖP-2025-00014 University Research Scholarship Programme of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund.