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Developmental and extracellular matrix-remodeling processes in rosiglitazone-exposed neonatal rat cardiomyocytes
Paul Paolini1, Daniel Pick, Jennifer Lapira
1Department of Biology, San Diego State University, CA, USA.
Objective:
The objective of this study was to investigate the effects of rosiglitazone (Avandia(®)) on gene expression in neonatal rat ventricular myocytes.
Materials & Methods:
Myocytes were exposed to rosiglitazone ex vivo. The two factors examined in the experiment were drug exposure (rosiglitazone and dimethyl sulfoxide vs dimethyl sulfoxide), and length of exposure to drug (½ h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 18 h, 24 h, 36 h and 48 h).
Results:
Transcripts that were consistently expressed in response to the drug were identified. Cardiovascular system development, extracellular matrix and immune response are represented prominently among the significantly modified gene ontology terms.
Conclusion:
Hmgcs2, Angptl4, Cpt1a, Cyp1b1, Ech1 and Nqo1 mRNAs were strongly upregulated in cells exposed to rosiglitazone. Enrichment of transcripts involved in cardiac muscle cell differentiation and the extracellular matrix provides a panel of biomarkers for further analysis in the context of adverse cardiac outcomes in humans. Original submitted 15 November 2013; Revision submitted 14 February 2014.
Insights
Rosiglitazone (Avandia) significantly altered gene expression in neonatal rat heart cells, upregulating genes involved in cardiovascular development and the extracellular matrix. This suggests potential biomarkers for adverse cardiac events in humans.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Pharmacology
Background:
- Neonatal rat ventricular myocytes are a model for studying cardiac gene expression.
- Rosiglitazone is a medication with known effects on metabolic pathways.
Purpose of the Study:
- Investigate the impact of rosiglitazone on gene expression in neonatal rat ventricular myocytes.
- Identify specific genes and pathways affected by rosiglitazone exposure.
Main Methods:
- Ex vivo exposure of myocytes to rosiglitazone for varying durations (0.5 to 48 hours).
- Analysis of gene expression changes in response to rosiglitazone treatment.
- Identification of significantly modified gene ontology terms.
Main Results:
- Rosiglitazone exposure led to consistent changes in transcript expression.
- Upregulation of Hmgcs2, Angptl4, Cpt1a, Cyp1b1, Ech1, and Nqo1 mRNAs observed.
- Enrichment of transcripts related to cardiovascular system development, extracellular matrix, and immune response.
Conclusions:
- Gene expression alterations in response to rosiglitazone highlight pathways critical for cardiac function.
- Identified upregulated genes and enriched pathways may serve as biomarkers for adverse cardiac outcomes.
- Further analysis is warranted to understand the clinical implications of these findings in humans.
