Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism, intervention, and long-term consequences.
<h4>Background</h4>Intrauterine growth restriction is associated with an increased future risk for developing cardiovascular diseases. Hypoxia in utero is a common clinical cause of fetal growth restriction. We have previously shown that chronic hypoxia alters cardiovascular development...
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Public Library of Science (PLoS)
2009-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0005155&type=printable |
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| author | Andrei Tintu Ellen Rouwet Stefan Verlohren Joep Brinkmann Shakil Ahmad Fatima Crispi Marc van Bilsen Peter Carmeliet Anne Cathrine Staff Marc Tjwa Irene Cetin Eduard Gratacos Edgar Hernandez-Andrade Leo Hofstra Michael Jacobs Wouter H Lamers Ingo Morano Erdal Safak Asif Ahmed Ferdinand le Noble |
| author_facet | Andrei Tintu Ellen Rouwet Stefan Verlohren Joep Brinkmann Shakil Ahmad Fatima Crispi Marc van Bilsen Peter Carmeliet Anne Cathrine Staff Marc Tjwa Irene Cetin Eduard Gratacos Edgar Hernandez-Andrade Leo Hofstra Michael Jacobs Wouter H Lamers Ingo Morano Erdal Safak Asif Ahmed Ferdinand le Noble |
| author_sort | Andrei Tintu |
| collection | DOAJ |
| description | <h4>Background</h4>Intrauterine growth restriction is associated with an increased future risk for developing cardiovascular diseases. Hypoxia in utero is a common clinical cause of fetal growth restriction. We have previously shown that chronic hypoxia alters cardiovascular development in chick embryos. The aim of this study was to further characterize cardiac disease in hypoxic chick embryos.<h4>Methods</h4>Chick embryos were exposed to hypoxia and cardiac structure was examined by histological methods one day prior to hatching (E20) and at adulthood. Cardiac function was assessed in vivo by echocardiography and ex vivo by contractility measurements in isolated heart muscle bundles and isolated cardiomyocytes. Chick embryos were exposed to vascular endothelial growth factor (VEGF) and its scavenger soluble VEGF receptor-1 (sFlt-1) to investigate the potential role of this hypoxia-regulated cytokine.<h4>Principal findings</h4>Growth restricted hypoxic chick embryos showed cardiomyopathy as evidenced by left ventricular (LV) dilatation, reduced ventricular wall mass and increased apoptosis. Hypoxic hearts displayed pump dysfunction with decreased LV ejection fractions, accompanied by signs of diastolic dysfunction. Cardiomyopathy caused by hypoxia persisted into adulthood. Hypoxic embryonic hearts showed increases in VEGF expression. Systemic administration of rhVEGF(165) to normoxic chick embryos resulted in LV dilatation and a dose-dependent loss of LV wall mass. Lowering VEGF levels in hypoxic embryonic chick hearts by systemic administration of sFlt-1 yielded an almost complete normalization of the phenotype.<h4>Conclusions/significance</h4>Our data show that hypoxia causes a decreased cardiac performance and cardiomyopathy in chick embryos, involving a significant VEGF-mediated component. This cardiomyopathy persists into adulthood. |
| format | Article |
| id | doaj-art-f94e4ab0c7db40d088273cfe1bd108d2 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2009-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-f94e4ab0c7db40d088273cfe1bd108d22025-08-20T03:22:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0144e515510.1371/journal.pone.0005155Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism, intervention, and long-term consequences.Andrei TintuEllen RouwetStefan VerlohrenJoep BrinkmannShakil AhmadFatima CrispiMarc van BilsenPeter CarmelietAnne Cathrine StaffMarc TjwaIrene CetinEduard GratacosEdgar Hernandez-AndradeLeo HofstraMichael JacobsWouter H LamersIngo MoranoErdal SafakAsif AhmedFerdinand le Noble<h4>Background</h4>Intrauterine growth restriction is associated with an increased future risk for developing cardiovascular diseases. Hypoxia in utero is a common clinical cause of fetal growth restriction. We have previously shown that chronic hypoxia alters cardiovascular development in chick embryos. The aim of this study was to further characterize cardiac disease in hypoxic chick embryos.<h4>Methods</h4>Chick embryos were exposed to hypoxia and cardiac structure was examined by histological methods one day prior to hatching (E20) and at adulthood. Cardiac function was assessed in vivo by echocardiography and ex vivo by contractility measurements in isolated heart muscle bundles and isolated cardiomyocytes. Chick embryos were exposed to vascular endothelial growth factor (VEGF) and its scavenger soluble VEGF receptor-1 (sFlt-1) to investigate the potential role of this hypoxia-regulated cytokine.<h4>Principal findings</h4>Growth restricted hypoxic chick embryos showed cardiomyopathy as evidenced by left ventricular (LV) dilatation, reduced ventricular wall mass and increased apoptosis. Hypoxic hearts displayed pump dysfunction with decreased LV ejection fractions, accompanied by signs of diastolic dysfunction. Cardiomyopathy caused by hypoxia persisted into adulthood. Hypoxic embryonic hearts showed increases in VEGF expression. Systemic administration of rhVEGF(165) to normoxic chick embryos resulted in LV dilatation and a dose-dependent loss of LV wall mass. Lowering VEGF levels in hypoxic embryonic chick hearts by systemic administration of sFlt-1 yielded an almost complete normalization of the phenotype.<h4>Conclusions/significance</h4>Our data show that hypoxia causes a decreased cardiac performance and cardiomyopathy in chick embryos, involving a significant VEGF-mediated component. This cardiomyopathy persists into adulthood.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0005155&type=printable |
| spellingShingle | Andrei Tintu Ellen Rouwet Stefan Verlohren Joep Brinkmann Shakil Ahmad Fatima Crispi Marc van Bilsen Peter Carmeliet Anne Cathrine Staff Marc Tjwa Irene Cetin Eduard Gratacos Edgar Hernandez-Andrade Leo Hofstra Michael Jacobs Wouter H Lamers Ingo Morano Erdal Safak Asif Ahmed Ferdinand le Noble Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism, intervention, and long-term consequences. PLoS ONE |
| title | Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism, intervention, and long-term consequences. |
| title_full | Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism, intervention, and long-term consequences. |
| title_fullStr | Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism, intervention, and long-term consequences. |
| title_full_unstemmed | Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism, intervention, and long-term consequences. |
| title_short | Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism, intervention, and long-term consequences. |
| title_sort | hypoxia induces dilated cardiomyopathy in the chick embryo mechanism intervention and long term consequences |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0005155&type=printable |
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