title: Homocysteine induces endothelial cell detachment and vessel wall thickening during chick embryonic development.
abstract: Homocysteine affects the migration and differentiation of neural crest cells in vitro and can result in neural tube defects in vivo. Furthermore, homocysteine has been described as an important determinant in vascular disease in human adults. However, little is known about the effects of homocysteine on the development of embryonic vessels. In this study, we injected homocysteine (30 micromol/L) into the neural tube lumen of chick embryos at the time point of neural crest cell emigration, and analyzed the effects on the neural crest-derived pharyngeal arch arteries, like the brachiocephalic arteries, and the mesoderm-derived arteries, such as the dorsal aorta. By stage HH35, we observed detachment of the endothelium, decreased expression of the extracellular matrix proteins fibrillin-2, and fibronectin in the pharyngeal arch arteries, whereas the dorsal aorta was identical in homocysteine-neural tube-injected and control embryos. No effect of homocysteine on endothelin-1 mRNA expression was observed. By stage HH40, the brachiocephalic arteries of homocysteine-neural tube-injected embryos displayed a decreased lumen diameter, an increased intima- and media-thickness, and an increased number of actin layers compared with the brachiocephalic arteries in control embryos. We propose that homocysteine affects the neural crest-derived smooth muscle cells and their extracellular matrix proteins in the pharyngeal arch arteries, resulting in an abnormal smooth muscle to endothelial cell interaction, leading to endothelial cell detachment. We suggest that, as in adult life, increased homocysteine concentrations lead to vascular damage in the embryo. This prenatal damage might increase the susceptibility to develop vessel pathology later in life.
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marit J
authors.initials: MJ
authors.lastname: Boot
authors.forename: Régine P M
authors.initials: RP
authors.lastname: Steegers-Theunissen
authors.forename: Robert E
authors.initials: RE
authors.lastname: Poelmann
authors.forename: Liesbeth
authors.initials: L
authors.lastname: van Iperen
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Gittenberger-de Groot
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D001934:Branchial Region / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D019070:Cell Lineage; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo; D019332:Endothelin-1 / Q000096:biosynthesis / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D000071840:Fibrillin-2; D000071837:Fibrillins; D005353:Fibronectins / Q000096:biosynthesis / Q000235:genetics; D006710:Homocysteine / Q000633:toxicity*; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D009432:Neural Crest / Q000166:cytology; D009436:Neural Tube Defects / Q000139:chemically induced; D013047:Specific Pathogen-Free Organisms
chemical_list: D019332:Endothelin-1; C000605723:FBN2 protein, human; D000071840:Fibrillin-2; D000071837:Fibrillins; D005353:Fibronectins; D008840:Microfilament Proteins; D006710:Homocysteine