The effects of rosiglitazone on the neonatal rat cardiomyocyte transcriptome: a temporal analysis

Abraham da Silveira, Willian; Vazquez-Hidalgo, Esteban; Bartolotta, Elesha; Renaud, Ludivine; Paolini, Paul; Hardiman, Gary

Abstract

Aim: The objective was to determine via high-throughput RNA sequencing the temporal effects of rosiglitazone (Avandia®) on the neonatal rat ventricular myocyte transcriptome.

Materials & methods: Neonatal rat ventricular myocytes (NRVMs) were exposed to rosiglitazone in vitro. Meta analyses utilized temporal comparisons of 0.5 h control versus 0.5 h treatment, 0.5 h treatment versus 24 h treatment and 24 h treatment versus 48 h treatment.

Results: Time dependent responses were observed. At 0.5 h, the PI3K-AKT signaling pathway was impacted. At 24 h endoplasmic reticulum activity and protein degradation were altered. At 48 h, oxytocin signaling was perturbed.

Conclusion: The effects of rosiglitazone occured early and increased in magnitude over time. A protective molecular response was triggered at 24 h and maintained until 48 h. In parallel, a response that can cause cardiac damage was activated. Our findings suggest that rosiglitazone has deleterious effects.

Citation

Abraham da Silveira, W., Vazquez-Hidalgo, E., Bartolotta, E., Renaud, L., Paolini, P., & Hardiman, G. (2019). The effects of rosiglitazone on the neonatal rat cardiomyocyte transcriptome: a temporal analysis. Pharmacogenomics, 20(16), 1125-1141. https://doi.org/10.2217/pgs-2019-0077

• Journal Article Type: Article
• Acceptance Date: Sep 17, 2019
• Online Publication Date: Nov 22, 2019
• Publication Date: Nov 22, 2019
• Deposit Date: Oct 25, 2024
• Journal: Pharmacogenomics
• Print ISSN: 1462-2416
• Electronic ISSN: 1744-8042
• Publisher: Future Medicine
• Peer Reviewed: Peer Reviewed
• Volume: 20
• Issue: 16
• Pages: 1125-1141
• DOI: https://doi.org/10.2217/pgs-2019-0077
• PMID: 31755367