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

    11 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

    Fingerprint

    Ductus Arteriosus
    Patent Ductus Arteriosus
    Elastic Tissue
    Chromosomes, Human, Pair 8
    Chromosomes, Human, Pair 9
    Genes
    Microarray Analysis
    Oligonucleotide Array Sequence Analysis
    Inbred BN Rats
    Prostaglandin E Receptors
    Newborn Infant
    Phenotype
    Quantitative Trait Loci
    Norway
    Molecular Biology
    Down-Regulation
    DNA

    Keywords

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

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

    Cite this

    Hsieh, Y. T., Liu, N. M., Ohmori, E., Yokota, T., Kajimura, I., Akaike, T., ... Minamisawa, S. (2014). Transcription profiles of the ductus arteriosus in Brown-Norway rats with irregular elastic fiber formation. Circulation Journal, 78(5), 1224-1233. https://doi.org/10.1253/circj.CJ-13-1029

    Transcription profiles of the ductus arteriosus in Brown-Norway rats with irregular elastic fiber formation. / Hsieh, Yi Ting; Liu, Norika Mengchia; Ohmori, Eriko; Yokota, Tomohiro; Kajimura, Ichige; Akaike, Toru; Ohshima, Toshio; Goda, Nobuhito; Minamisawa, Susumu.

    In: Circulation Journal, Vol. 78, No. 5, 2014, p. 1224-1233.

    Research output: Contribution to journalArticle

    Hsieh, Yi Ting ; Liu, Norika Mengchia ; Ohmori, Eriko ; Yokota, Tomohiro ; Kajimura, Ichige ; Akaike, Toru ; Ohshima, Toshio ; Goda, Nobuhito ; Minamisawa, Susumu. / Transcription profiles of the ductus arteriosus in Brown-Norway rats with irregular elastic fiber formation. In: Circulation Journal. 2014 ; Vol. 78, No. 5. pp. 1224-1233.
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    keywords = "Congenital heart disease, DNA microarray, Elastic fiber, Patent ductus arteriosus, Vascular remodeling",
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    AU - Liu, Norika Mengchia

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    AU - Yokota, Tomohiro

    AU - Kajimura, Ichige

    AU - Akaike, Toru

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    AU - Goda, Nobuhito

    AU - Minamisawa, Susumu

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    AB - 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.

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