Disturbed morphogenesis of cardiac outflow tract and increased rate of aortic arch anomalies in the offspring of diabetic rats

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Fältnamn	Indikatorer	Metadata
000		04012naa a2200541 4500
001		oai:DiVA.org:uu-73554
003		SwePub
008		071116s2004 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-735542 URI
040		a (SwePub)uu
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Molin, Daniël G M4 aut
245	1 0	a Disturbed morphogenesis of cardiac outflow tract and increased rate of aortic arch anomalies in the offspring of diabetic rats
264	1	c 2004
338		a print2 rdacarrier
520		a BACKGROUND: Maternal diabetes (MD) is a risk factor for offspring to develop cardiovascular anomalies; this is of growing clinical concern since the number of women in childbearing age with compromised glucose homeostasis is increasing. Hyperglycemia abrogates cardiovascular development in vitro; however, a link to cardiovascular defects in diabetic offspring remains to be investigated. METHODS: We have studied cardiovascular development in offspring of MD rats by examining serial histological sections of GD 12.0-18.0 offspring. Development of pharyngeal arch artery malformations was analyzed and related to intracardiac anomalies. RESULTS: Pharyngeal arch artery and intracardiac defects were present in 27 of 37 MD GD 13.0-18.0 offspring. Early sixth arch arteries showed abrogated arteriogenesis, whereas fourth arch artery defects developed as a result of abnormal remodeling. Morphometrical analysis showed increased apoptosis in regressing artery segments and reduced apoptosis in persisting artery segments. Double outlet right ventricle with infundibular stenosis (tetralogy of Fallot) was predominantly found in combination with sixth artery defects and pulmonary atresia. As confirmed by morphometric analysis and three-dimensional (3D)-reconstructions, outflow tract defects coincided with endocardial cushion hypoplasia. Cases with teratology of Fallot additionally showed a shorter outflow tract. No relation with apoptosis or disturbed neural crest cell migration was found. CONCLUSIONS: Our data uniquely demonstrate mechanistic differences involved in the development of sixth and fourth artery anomalies. Whereas increased apoptosis induces fourth artery anomalies, pulmonary outflow obstruction abrogates sixth artery differentiation independent of apoptosis. The model presented allows analysis of diabetic conditions on cardiovascular development in vivo, essential for elucidating this teratology.
653		a Animals
653		a Aorta; Thoracic/abnormalities/embryology
653		a Apoptosis
653		a Coronary Circulation
653		a Diabetes Complications/*embryology/veterinary
653		a Disease Models; Animal
653		a Female
653		a Fetal Development
653		a Humans
653		a Hyperglycemia/*complications/veterinary
653		a Male
653		a Pregnancy
653		a Pregnancy Complications
653		a Rats
653		a Rats; Sprague-Dawley
653		a Regional Blood Flow
653		a Research Support; U.S. Gov't; P.H.S.
653		a Risk Factors
653		a Tetralogy of Fallot/*etiology
700	1	a Roest, Pauline A M4 aut
700	1	a Nordstrand, Hannau Uppsala universitet,Institutionen för medicinsk cellbiologi4 aut
700	1	a Wisse, Lambertus J4 aut
700	1	a Poelmann, Robert E4 aut
700	1	a Eriksson, Ulf Ju Uppsala universitet,Institutionen för medicinsk cellbiologi4 aut
700	1	a Gittenberger-De Groot, Adriana C4 aut
710	2	a Uppsala universitetb Institutionen för medicinsk cellbiologi4 org
773	0	t Birth Defects Research. Part A. Clinical and Molecular Teratologyg 70:12, s. 927-938q 70:12<927-938x 1542-0752
856	4	u http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=15578651&dopt=Citation
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-73554

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Av författaren/redakt...: Molin, Daniël G ...; Roest, Pauline A ...; Nordstrand, Hann ...; Wisse, Lambertus ...; Poelmann, Robert ...; Eriksson, Ulf J; visa fler...; Gittenberger-De ...; visa färre...

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