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(Circulation Research. 2005;96:1291.)
© 2005 American Heart Association, Inc.

Integrative Physiology

Changes in Shear Stress–Related Gene Expression After Experimentally Altered Venous Return in the Chicken Embryo

Bianca C.W. Groenendijk, Beerend P. Hierck, Johannes Vrolijk, Martin Baiker, Mathieu J.B.M. Pourquie, Adriana C. Gittenberger-de Groot, Robert E. Poelmann

From the Department of Anatomy and Embryology (B.C.W.G., B.P.H., M.B., A.C.G.-d.G., R.E.P.) and the Laboratory for Cytochemistry and Cytometry, Department of Molecular Cell Biology (J.V.), Leiden University Medical Center, Leiden, The Netherlands; and the Department of Aero- and Hydro-dynamics (M.B., M.J.B.M.P.), Delft University of Technology, Delft, The Netherlands.

Correspondence to Dr R.E. Poelmann, Department of Anatomy and Embryology, Leiden University Medical Center, PO Box 9602, 2300 RC Leiden, The Netherlands. E-mail R.E.Poelmann{at}lumc.nl

Hemodynamics play an important role in cardiovascular development, and changes in blood flow can cause congenital heart malformations. The endothelium and endocardium are subjected to mechanical forces, of which fluid shear stress is correlated to blood flow velocity. The shear stress responsive genes lung Krüppel-like factor (KLF2), endothelin-1 (ET-1), and endothelial nitric oxide synthase (NOS-3) display specific expression patterns in vivo during chicken cardiovascular development. Nonoverlapping patterns of these genes were demonstrated in the endocardium at structural lumen constrictions that are subjected to high blood flow velocities. Previously, we described in chicken embryos a dynamic flow model (the venous clip) in which the venous return to the heart is altered and cardiac blood flow patterns are disturbed, causing the formation of congenital cardiac malformations. In the present study we test the hypothesis that disturbed blood flow can induce altered gene expression. In situ hybridizations indeed show a change in gene expression after venous clip. The level of expression of ET-1 in the heart is locally decreased, whereas KLF2 and NOS-3 are both upregulated. We conclude that venous obstruction results in altered expression patterns of KLF2, ET-1, and NOS-3, suggestive for increased cardiac shear stress.

Key Words: cardiovascular physiology • embryonic circulation • endothelium • gene expression • shear stress

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