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

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.

Developmental and extracellular matrix-remodeling processes in rosiglitazone-exposed neonatal rat cardiomyocytes.

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.

Contractility assessment in enzymatically isolated cardiomyocytes.

The use of enzymatically isolated cardiac myocytes is ubiquitous in modern cardiovascular research. Parallels established between cardiomyocyte shortening responses and those of intact tissue make the cardiomyocyte an invaluable experimental model of cardiac function. Much of our understanding regarding the fundamental processes underlying heart function is owed to our increasing capabilities in single-cell stimulation and direct or indirect observation, as well as quantitative analysis of such cells. Of the many important mechanisms and functions that can be readily assessed in cardiomyocytes at all stages of development, contractility is the most representative and one of the most revealing. The purpose of this review is to provide a survey of various methodological approaches in the literature used to assess adult and neonatal cardiomyocyte contractility. The various methods employed to evaluate the contractile behavior of enzymatically isolated mammalian cardiac myocytes can be conveniently divided into two general categories-those employing optical (image)-based systems and those that use transducer-based technologies. This survey is by no means complete, but we have made an effort to include the most popular methods in terms of reliability and accessibility. These techniques are in constant evolution and hold great promise for the next generation of breakthrough studies in cell biology for the prevention, treatment, and cure of cardiovascular diseases.