L59	Vascular remodelling: differentiation of arteries, veins and lymph vessels.
1A.Gittenberger-de Groot, 1N.van den Akker, 2M.Bekker, 3D.Molin, 1R.Poelmann
1Leiden University Medical Center, Dept. of Anatomy & Embryology, Leiden, NL; 2Free University Medical Center, Dept. of Gynaecology, Amsterdam, NL; 3University Maastricht, Dept. of Physiology, Maastricht, NL.

The intraembryonic vasculature starts with endothelial differentiation and tube formation. Artery and vein stabilisation is acquired by addition of pericytes and smooth muscle cells (SMC). In this process the endothelial cells lining the blood vessels (BEC) and lymph vessels (LEC) express characteristic differentiation markers. BECs of arteries (ephrinB2+, NP1+) and veins (ephrinB4+, NP2+) differ from the LEC lining the lymph vessels (Prox1+, LYVE1+, podoplanin+). SMCs are specific for arteries and veins, while lymph vessels lack SMCs. Study of mouse (trisomy 16) and human (trisomy 21) models with nuchal lymphedema show an essential role for podoplanin and Prox1 in directing vascular differentiation in lymphatic directions. A fluid disbalance, as seen in lymphedema, is accompanied by a loss of LEC identity and vascular wall morphology. Specifically ectopic expression of VEGFA-isoforms and its receptor NP1 is found in cases with abnormal remodelling of the nuchal region, aortic arch system and coronary vasculature. These findings are supported by data of VEGF120/120 mice. A marked role for abberant apoptosis in aorta arch remodelling abnormalities can be linked to flow and shear stress responsive genes (ET1, TGFb1, PDGF, VEGF). Interestingly these genes are also expressed in nerves, emphasizing a close interaction between angiogenesis and neurogenesis for vascular differentiation.

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