Transcription Profiles of the Ductus Arteriosus in Brown-Norway Rats With Irregular Elastic Fiber Formation
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...
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| Veröffentlicht in: | Circulation Journal 2014, Vol.78(5), pp.1224-1233 |
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| creator | Hsieh, Yi-Ting Liu, Norika Mengchia Ohmori, Eriko Yokota, Tomohiro Kajimura, Ichige Akaike, Toru Ohshima, Toshio Goda, Nobuhito Minamisawa, Susumu |
| description | 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 |
| doi_str_mv | 10.1253/circj.CJ-13-1029 |
| format | Article |
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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. (Circ J 2014; 78: 1224–1233)</description><identifier>ISSN: 1346-9843</identifier><identifier>EISSN: 1347-4820</identifier><identifier>DOI: 10.1253/circj.CJ-13-1029</identifier><identifier>PMID: 24647370</identifier><language>eng</language><publisher>Japan: The Japanese Circulation Society</publisher><subject>Animals ; Animals, Newborn ; Chromosomes, Mammalian - genetics ; Congenital heart disease ; DNA microarray ; Ductus Arteriosus - metabolism ; Ductus Arteriosus - pathology ; Ductus Arteriosus, Patent - genetics ; Ductus Arteriosus, Patent - metabolism ; Ductus Arteriosus, Patent - pathology ; Elastic fiber ; Elastic Tissue - metabolism ; Elastic Tissue - pathology ; Gene Expression Regulation ; Muscle Proteins - biosynthesis ; Muscle Proteins - genetics ; Patent ductus arteriosus ; Quantitative Trait Loci ; Rats ; Rats, Inbred F344 ; Transcription, Genetic ; Vascular remodeling</subject><ispartof>Circulation Journal, 2014, Vol.78(5), pp.1224-1233</ispartof><rights>2014 THE JAPANESE CIRCULATION SOCIETY</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c494t-183afcd5e63c1efda65df14b0df7c1eed3bf413c1fc667525c54cd3675f7305a3</citedby><cites>FETCH-LOGICAL-c494t-183afcd5e63c1efda65df14b0df7c1eed3bf413c1fc667525c54cd3675f7305a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,4010,27902,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24647370$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hsieh, Yi-Ting</creatorcontrib><creatorcontrib>Liu, Norika Mengchia</creatorcontrib><creatorcontrib>Ohmori, Eriko</creatorcontrib><creatorcontrib>Yokota, Tomohiro</creatorcontrib><creatorcontrib>Kajimura, Ichige</creatorcontrib><creatorcontrib>Akaike, Toru</creatorcontrib><creatorcontrib>Ohshima, Toshio</creatorcontrib><creatorcontrib>Goda, Nobuhito</creatorcontrib><creatorcontrib>Minamisawa, Susumu</creatorcontrib><title>Transcription Profiles of the Ductus Arteriosus in Brown-Norway Rats With Irregular Elastic Fiber Formation</title><title>Circulation Journal</title><addtitle>Circ J</addtitle><description>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. (Circ J 2014; 78: 1224–1233)</description><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Chromosomes, Mammalian - genetics</subject><subject>Congenital heart disease</subject><subject>DNA microarray</subject><subject>Ductus Arteriosus - metabolism</subject><subject>Ductus Arteriosus - pathology</subject><subject>Ductus Arteriosus, Patent - genetics</subject><subject>Ductus Arteriosus, Patent - metabolism</subject><subject>Ductus Arteriosus, Patent - pathology</subject><subject>Elastic fiber</subject><subject>Elastic Tissue - metabolism</subject><subject>Elastic Tissue - pathology</subject><subject>Gene Expression Regulation</subject><subject>Muscle Proteins - biosynthesis</subject><subject>Muscle Proteins - genetics</subject><subject>Patent ductus arteriosus</subject><subject>Quantitative Trait Loci</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Transcription, Genetic</subject><subject>Vascular remodeling</subject><issn>1346-9843</issn><issn>1347-4820</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1PGzEQhi3UCij0zgn52MuCvbb34wgpKSAECIF6tBzvmDhs1mHsFeLf1yEpXGZe2c88h5eQI85OeKnEqfVoFyeT64KLgrOy3SH7XMi6kE3Jvn3kqmgbKfbIjxgXLBNMtbtkr5SVrEXN9snLI5ohWvSr5MNA7zE430OkwdE0B_p7tGmM9AwToA8xRz_QcwxvQ3Eb8M280weTIv3r05xeIcLz2BukF72JyVs69TNAOg24NGv7IfnuTB_h53YfkKfpxePksri5-3M1ObsprGxlKngjjLOdgkpYDq4zleoclzPWuTo_QCdmTvL852xV1apUVknbiRxdLZgy4oD82nhXGF5HiEkvfbTQ92aAMEbNFW8b0TLOMso2qMUQI4LTK_RLg--aM72uWH9UrCfXmgu9rjifHG_t42wJ3efB_04zMN0Ai5jMM3wCBnMnPWyNdaPVenyZv4C5QQ2D-AeYHpO9</recordid><startdate>2014</startdate><enddate>2014</enddate><creator>Hsieh, Yi-Ting</creator><creator>Liu, Norika Mengchia</creator><creator>Ohmori, Eriko</creator><creator>Yokota, Tomohiro</creator><creator>Kajimura, Ichige</creator><creator>Akaike, Toru</creator><creator>Ohshima, Toshio</creator><creator>Goda, Nobuhito</creator><creator>Minamisawa, Susumu</creator><general>The Japanese Circulation Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>2014</creationdate><title>Transcription Profiles of the Ductus Arteriosus in Brown-Norway Rats With Irregular Elastic Fiber Formation</title><author>Hsieh, Yi-Ting ; Liu, Norika Mengchia ; Ohmori, Eriko ; Yokota, Tomohiro ; Kajimura, Ichige ; Akaike, Toru ; Ohshima, Toshio ; Goda, Nobuhito ; Minamisawa, Susumu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c494t-183afcd5e63c1efda65df14b0df7c1eed3bf413c1fc667525c54cd3675f7305a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Chromosomes, Mammalian - genetics</topic><topic>Congenital heart disease</topic><topic>DNA microarray</topic><topic>Ductus Arteriosus - metabolism</topic><topic>Ductus Arteriosus - pathology</topic><topic>Ductus Arteriosus, Patent - genetics</topic><topic>Ductus Arteriosus, Patent - metabolism</topic><topic>Ductus Arteriosus, Patent - pathology</topic><topic>Elastic fiber</topic><topic>Elastic Tissue - metabolism</topic><topic>Elastic Tissue - pathology</topic><topic>Gene Expression Regulation</topic><topic>Muscle Proteins - biosynthesis</topic><topic>Muscle Proteins - genetics</topic><topic>Patent ductus arteriosus</topic><topic>Quantitative Trait Loci</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Transcription, Genetic</topic><topic>Vascular remodeling</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hsieh, Yi-Ting</creatorcontrib><creatorcontrib>Liu, Norika Mengchia</creatorcontrib><creatorcontrib>Ohmori, Eriko</creatorcontrib><creatorcontrib>Yokota, Tomohiro</creatorcontrib><creatorcontrib>Kajimura, Ichige</creatorcontrib><creatorcontrib>Akaike, Toru</creatorcontrib><creatorcontrib>Ohshima, Toshio</creatorcontrib><creatorcontrib>Goda, Nobuhito</creatorcontrib><creatorcontrib>Minamisawa, Susumu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation Journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hsieh, Yi-Ting</au><au>Liu, Norika Mengchia</au><au>Ohmori, Eriko</au><au>Yokota, Tomohiro</au><au>Kajimura, Ichige</au><au>Akaike, Toru</au><au>Ohshima, Toshio</au><au>Goda, Nobuhito</au><au>Minamisawa, Susumu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcription Profiles of the Ductus Arteriosus in Brown-Norway Rats With Irregular Elastic Fiber Formation</atitle><jtitle>Circulation Journal</jtitle><addtitle>Circ J</addtitle><date>2014</date><risdate>2014</risdate><volume>78</volume><issue>5</issue><spage>1224</spage><epage>1233</epage><pages>1224-1233</pages><issn>1346-9843</issn><eissn>1347-4820</eissn><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. (Circ J 2014; 78: 1224–1233)</abstract><cop>Japan</cop><pub>The Japanese Circulation Society</pub><pmid>24647370</pmid><doi>10.1253/circj.CJ-13-1029</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Animals, Newborn Chromosomes, Mammalian - genetics Congenital heart disease DNA microarray Ductus Arteriosus - metabolism Ductus Arteriosus - pathology Ductus Arteriosus, Patent - genetics Ductus Arteriosus, Patent - metabolism Ductus Arteriosus, Patent - pathology Elastic fiber Elastic Tissue - metabolism Elastic Tissue - pathology Gene Expression Regulation Muscle Proteins - biosynthesis Muscle Proteins - genetics Patent ductus arteriosus Quantitative Trait Loci Rats Rats, Inbred F344 Transcription, Genetic Vascular remodeling |
| title | Transcription Profiles of the Ductus Arteriosus in Brown-Norway Rats With Irregular Elastic Fiber Formation |
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