Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/96032
Title: Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism; intervention; and long-term consequences.
Author: Tintu, Andrei
Rouwet, Ellen
Verlohren, Stefan
Brinkmann, Joep
Ahmad, Shakil
Crispi Brillas, Fàtima
van Bilsen, Marc
Carmeliet, Peter
Staff, Anne Cathrine
Tjwa, Marc
Cetin, Irene
Gratacós Solsona, Eduard
Hernandez-Andrade, Edgar
Hofstra, Leo
Jacobs, Michael
Lamers, Wouter H.
Morano, Ingo
Safak, Erdal
Ahmed, Asif
Le Noble, Ferdinand
Keywords: Anoxèmia
Creixement fetal
Cor
Malalties coronàries
Anoxemia
Fetal growth
Heart
Coronary diseases
Issue Date: 9-Apr-2009
Publisher: Public Library of Science (PLoS)
Abstract: Background 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. Methods 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. Principal Findings 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 rhVEGF165 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. Conclusions/Significance 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.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0005155
It is part of: PLoS One, 2009, vol. 4, num. 4, p. e5155
Related resource: http://dx.doi.org/10.1371/journal.pone.0005155
URI: http://hdl.handle.net/2445/96032
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Fonaments Clínics)

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