Willian Abraham da Silveira1,2, Esteban Vazquez-Hidalgo3,4, Elesha Bartolotta3, Ludivine Renaud1,5, Paul Paolini3,4, Gary Hardiman1,2,5. 1. Center for Genomic Medicine, Bioinformatics, Medical University of South Carolina, Charleston, SC, USA. 2. Faculty of Medicine, Health & Life Sciences, School of Biological Sciences, Institute for Global Food Security (IGFS), Belfast, Northern Ireland, UK. 3. Department of Biology, San Diego State University, San Diego, CA, USA. 4. Computational Science Research Center, San Diego State University, San Diego, CA, USA. 5. Department of Medicine, Medical University of South Carolina, Charleston, SC, USA.
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.
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.
Entities:
Keywords:
Avandia®; RNAseq; Type 2 diabetes mellitus; neonatal rat ventricular myocytes; peroxisome proliferator-activated receptor-gamma; rosiglitazone
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