Buschmann, Ivo Pries, Axel Styp-Rekowska, Beata Hillmeister, Philipp Loufrani, Laurent Henrion, Daniel Shi, Yu Duelsner, Andre Hoefer, Imo Gatzke, Nora Wang, Haitao Lehmann, Kerstin Ulm, Lena Ritter, Zully Hauff, Peter Hlushchuk, Ruslan Djonov, Valentin Veen, Toon van Le Noble, Ferdinand 2010 In the developing chicken embryo yolk sac vasculature, the expression of arterial identity genes requires arterial hemodynamic conditions. We hypothesize that arterial flow must provide a unique signal that is relevant for supporting arterial identity gene expression and is absent in veins. We analyzed factors related to flow, pressure and oxygenation in the chicken embryo vitelline vasculature in vivo. The best discrimination between arteries and veins was obtained by calculating the maximal pulsatile increase in shear rate relative to the time-averaged shear rate in the same vessel: the relative pulse slope index (RPSI). RPSI was significantly higher in arteries than veins. Arterial endothelial cells exposed to pulsatile shear in vitro augmented arterial marker expression as compared with exposure to constant shear. The expression of Gja5 correlated with arterial flow patterns: the redistribution of arterial flow provoked by vitelline artery ligation resulted in flow-driven collateral arterial network formation and was associated with increased expression of Gja5. In situ hybridization in normal and ligation embryos confirmed that Gja5 expression is confined to arteries and regulated by flow. In mice, Gja5 (connexin 40) was also expressed in arteries. In the adult, increased flow drives arteriogenesis and the formation of collateral arterial networks in peripheral occlusive diseases. Genetic ablation of Gja5 function in mice resulted in reduced arteriogenesis in two occlusion models. We conclude that pulsatile shear patterns may be central for supporting arterial identity, and that arterial Gja5 expression plays a functional role in flow-driven arteriogenesis. application/pdf https://folia.unifr.ch/global/documents/301757 https://folia.unifr.ch/documents/301757/files/hlu_psg.pdf https://folia.unifr.ch/documents/301757/files/hlu_psg_sm.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1242/dev.045351 info:eu-repo/semantics/openAccess License undefined Development. - 2010, vol. 137, p. 2187-2196 Gja5 (connexin 40) Arterial-venous differentiation Arteriogenesis Blood flow Pulsatile shear Chick Mouse info:eu-repo/classification/udc/57 Pulsatile shear and Gja5 modulate arterial identity and remodeling events during flow-driven arteriogenesis http://purl.org/coar/resource_type/c_6501