Cardiac outflow tract malformations in chick embryos exposed to homocysteine

MJ Boot, RPM Steegers-Theunissen… - Cardiovascular …, 2004 - academic.oup.com
MJ Boot, RPM Steegers-Theunissen, RE Poelmann, L van Iperen, AC Gittenberger-de Groot
Cardiovascular research, 2004academic.oup.com
Objective: Increased homocysteine concentrations have been associated with cardiac
outflow tract defects. It has been hypothesized that cardiac neural crest cells were the target
cells in these malformations. Cardiac neural crest cells migrate from the neural tube and
contribute to the condensed mesenchyme of the aorticopulmonary septum and outflow tract
cushions of the heart. The aim of this study is to investigate the effects of homocysteine on
cardiac neural crest cells in relation to heart malformations. Methods: Homocysteine was …
Abstract
Objective : Increased homocysteine concentrations have been associated with cardiac outflow tract defects. It has been hypothesized that cardiac neural crest cells were the target cells in these malformations. Cardiac neural crest cells migrate from the neural tube and contribute to the condensed mesenchyme of the aorticopulmonary septum and outflow tract cushions of the heart. The aim of this study is to investigate the effects of homocysteine on cardiac neural crest cells in relation to heart malformations.
Methods : Homocysteine was injected either into the neural tube lumen (30 μmol/l), or into the circulatory system (30 or 300 μmol/l) of chick embryos. LacZ-retroviral labeling was used to study cardiac neural crest cell migratory pathways after exposure to homocysteine.
Results : Cardiac neural crest cells contributed to the aorticopulmonary septum of both control and homocysteine-treated embryos. However, the outflow tract of homocysteine-neural tube injected embryos displayed 60% less apoptosis and 25% reduced myocardialization. A subarterial ventricular septal defect was observed in 83% of the embryos. None of these abnormalities were observed in homcysteine-circulatory system injected embryos.
Conclusion : This study demonstrates that homocysteine disturbs apoptosis and myocardialization of the outflow tract, probably by affecting the cardiac neural crest cells.
Oxford University Press