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

Paul Paolini, Daniel Pick, Jennifer Lapira, Giuseppina Sannino, Lorenza Pasqualini, Colleen Ludka, L. James Sprague, Xian Zhang, Elesha A. Bartolotta, Esteban Vazquez-Hidalgo, David Torres Barba, Carlos Bazan, Gary Hardiman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

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 (1/2 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 languageEnglish
Pages (from-to)759-774
Number of pages16
JournalPharmacogenomics
Volume15
Issue number6
DOIs
Publication statusPublished - 01 Jan 2014

Keywords

  • neonatal rat ventricular myocytes
  • NRVMs
  • peroxisome
  • PPAR-γ
  • proliferator-activated receptor-γ
  • rosiglitazone
  • T2DM
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

Fingerprint Dive into the research topics of 'Developmental and extracellular matrix-remodeling processes in rosiglitazone-exposed neonatal rat cardiomyocytes'. Together they form a unique fingerprint.

Cite this