TY  - JOUR
A1  - Tintu, Andrei
A1  - Rouwet, Ellen
A1  - Verlohren, Stefan
A1  - Brinkmann, Joep
A1  - Ahmad, Shakil
A1  - Crispi, Fatima
A1  - Bilsen, Marc van
A1  - Carmeliet, Peter
A1  - Staff, Anne Cathrine
A1  - Tjwa, Marc
A1  - Cetin, Irene
A1  - Gratacós, Eduard
A1  - Hernandez-Andrade, Edgar
A1  - Hofstra, Leo
A1  - Jacobs, Michael
A1  - Lamers, Wouter H.
A1  - Morano, Ingo
A1  - Safak, Erdal
A1  - Ahmed, Asif
A1  - Le Noble, Ferdinand
T1  - Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism, intervention, and long-term consequences
T2  - PLoS One
N2  - 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.
Y1  - 2009
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/22653
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-114982
SN  - 1932-6203
N1  - Copyright: © 2009 Tintu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 4
IS  - (4): e5155
ER  -