title: Developmental and extracellular matrix-remodeling processes in rosiglitazone-exposed neonatal rat cardiomyocytes.
abstract: OBJECTIVE
  The objective of this study was to investigate the effects of rosiglitazone (Avandia(®)) on gene expression in neonatal rat ventricular myocytes.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biology, San Diego State University, CA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Paolini
authors.forename: Daniel
authors.initials: D
authors.lastname: Pick
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lapira
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Sannino
authors.forename: Lorenza
authors.initials: L
authors.lastname: Pasqualini
authors.forename: Colleen
authors.initials: C
authors.lastname: Ludka
authors.forename: L James
authors.initials: LJ
authors.lastname: Sprague
authors.forename: Xian
authors.initials: X
authors.lastname: Zhang
authors.forename: Elesha A
authors.initials: EA
authors.lastname: Bartolotta
authors.forename: Esteban
authors.initials: E
authors.lastname: Vazquez-Hidalgo
authors.forename: David Torres
authors.initials: DT
authors.lastname: Barba
authors.forename: Carlos
authors.initials: C
authors.lastname: Bazan
authors.forename: Gary
authors.initials: G
authors.lastname: Hardiman
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D004121:Dimethyl Sulfoxide
keywords: Avandia®; NRVMs; PPAR-γ; T2DM; Type 2 diabetes mellitus; neonatal rat ventricular myocytes; peroxisome; proliferator-activated receptor-γ; rosiglitazone