Pulsatile shear and Gja5 modulate arterial identity and remodeling events during flow-driven arteriogenesis

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

doi:10.1242/dev.045351

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Pulsatile shear and Gja5 modulate arterial identity and remodeling events during flow-driven arteriogenesis

Buschmann, Ivo Experimental and Clinical Research Center (ECRC) of the Charite and the Max-Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany - Department of Internal Medicine/Cardiology, CCR, Charite, Berlin, Germany - Center for Stroke Research Berlin (CSB), Charite, Berlin, Germany
Pries, Axel Department of Physiology, CCR and German Heart Center, Charite, Berlin, Germany
Styp-Rekowska, Beata Department of Physiology, CCR and German Heart Center, Charite, Berlin, Germany
Hillmeister, Philipp Experimental and Clinical Research Center (ECRC) of the Charite and the Max-Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany - Center for Stroke Research Berlin (CSB), Charite, Berlin, Germany
Loufrani, Laurent Department of Neurovascular Biology, University of Angers, France
Henrion, Daniel Department of Neurovascular Biology, University of Angers, France
Shi, Yu Experimental and Clinical Research Center (ECRC) of the Charite and the Max-Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany
Duelsner, Andre Experimental and Clinical Research Center (ECRC) of the Charite and the Max-Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany
Hoefer, Imo Department of Experimental Cardiology, Division of Heart & Lungs, Utrecht, The Netherlands
Gatzke, Nora Experimental and Clinical Research Center (ECRC) of the Charite and the Max-Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany
Wang, Haitao Experimental and Clinical Research Center (ECRC) of the Charite and the Max-Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany
Lehmann, Kerstin Experimental and Clinical Research Center (ECRC) of the Charite and the Max-Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany
Ulm, Lena Department of Physiology, CCR and German Heart Center, Charite, Berlin, Germany
Ritter, Zully Department of Radiology, CBF, Charite, Berlin, Germany
Hauff, Peter Bayer Schering Pharma AG, MicroCT Unit, Berlin, Germany
Hlushchuk, Ruslan Department of Gross Anatomy and Vascular Biology, University of Fribourg, Switzerland
Djonov, Valentin Department of Gross Anatomy and Vascular Biology, University of Fribourg, Switzerland
Veen, Toon van Department of Medical Physiology, Division of Heart & Lungs, Utrecht, The Netherlands
Le Noble, Ferdinand Experimental and Clinical Research Center (ECRC) of the Charite and the Max-Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany - Center for Stroke Research Berlin (CSB), Charite, Berlin, Germany - Max-Delbrueck Center for Molecular Medicine (MDC), Department of Angiogenesis and Cardiovascular Pathology, Berlin, Germany

2010

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Development. - 2010, vol. 137, p. 2187-2196

Arterial-venous differentiation

English 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.

Faculty

Faculté des sciences et de médecine

Department

Département de Médecine

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