Assessment of the molecular mechanisms of drug‐induced hidden cardiotoxicity by a multi‐omics approach: The example of rofecoxib
This is the first demonstration that multi-omics characterisation can reveal underlying regulatory pathways of hidden cardiotoxicity. Importantly, our study shows that transcriptomics gives limited information on the hidden cardiotoxic effects of rofecoxib, which are mainly mediated by changes in posttranslational modifications and protein expression. These changes, among other mechanisms, may disturb the cardiac calcium handling, which could explain the fatal arrhythmias following ischaemia/reperfusion observed with rofecoxib.
Authors
- Barnabás Váradi
- Bence Ágg (ORCID: https://orcid.org/0000-0002-6492-0426)
- Csenger Kovácsházi (ORCID: https://orcid.org/0000-0003-0283-9486)
- Olivér M. Balogh (ORCID: https://orcid.org/0000-0002-6296-6383)
- Donagh Egan (ORCID: https://orcid.org/0000-0001-5324-3346)
- Anikó Görbe (ORCID: https://orcid.org/0000-0002-1680-9256)
- Gábor B. Brenner
- Bennet Y. Weber (ORCID: https://orcid.org/0000-0001-5065-1969)
- Zoltán Giricz (ORCID: https://orcid.org/0000-0003-2036-8665)
- Kieran J. Wynne (ORCID: https://orcid.org/0000-0001-5759-5285)
- David Matallanas (ORCID: https://orcid.org/0000-0002-2360-3141)
- Péter Ferdinandy
Institutions
- University College Dublin (IE)
- Semmelweis University (HU)
- Justus-Liebig-Universität Gießen (DE)
Publication Details
- Journal
- British Journal of Pharmacology
- Published
- 2025-06-18
- DOI
- https://doi.org/10.1111/bph.70106
- Citations
- 2
- Primary Topic
- Receptor Mechanisms and Signaling
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- European Commission
- Science Foundation Ireland
- Semmelweis Egyetem
- Nemzeti Kutatási Fejlesztési és Innovációs Hivatal
- Innovációs és Technológiai Minisztérium
- Nemzeti Kutatási, Fejlesztési és Innovaciós Alap
- National Research, Development and Innovation Office