Transcription profiles of the ductus arteriosus in Brown-Norway rats with irregular elastic fiber formation

Yi Ting Hsieh, Norika Mengchia Liu, Eriko Ohmori, Tomohiro Yokota, Ichige Kajimura, Toru Akaike, Toshio Ohshima, Nobuhito Goda, Susumu Minamisawa

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Patent ductus arteriosus (PDA) is one of the most common congenital cardiovascular defects in children. The Brown-Norway (BN) inbred rat presents a higher frequency of PDA. A previous study reported that 2 different quantitative trait loci on chromosomes 8 and 9 were significantly linked to PDA in this strain. Nevertheless, the genetic or molecular mechanisms underlying PDA phenotypes in BN rats have not been fully investigated yet. Methods and Results: It was found that the elastic fibers were abundant in the subendothelial area but scarce in the media even in the closed ductus arteriosus (DA) of full-term BN neonates. DNA microarray analysis identified 52 upregulated genes (fold difference >2.5) and 23 downregulated genes (fold difference <0.4) when compared with those of F344 control neonates. Among these genes, 8 (Tbx20, Scn3b, Stac, Sphkap, Trpm8, Rup2, Slc37a2, and RGD1561216) are located in chromosomes 8 and 9. Interestingly, it was also suggested that the significant decrease in the expression levels of the PGE2-specfic receptor, EP4, plays a critical role in elastogenesis in the DA. Conclusions: BN rats exhibited dysregulation of elastogenesis in the DA. DNA microarray analysis identified the candidate genes including EP4 involved in the DNA phenotype. Further investigation of these newly identified genes will hopefully clarify the molecular mechanisms underlying the irregular formation of elastic fibers in PDA.

Original languageEnglish
Pages (from-to)1224-1233
Number of pages10
JournalCirculation Journal
Volume78
Issue number5
DOIs
Publication statusPublished - 2014

Keywords

  • Congenital heart disease
  • DNA microarray
  • Elastic fiber
  • Patent ductus arteriosus
  • Vascular remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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