title: Changes in shear stress-related gene expression after experimentally altered venous return in the chicken embryo.
abstract: 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.
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Bianca C W
authors.initials: BC
authors.lastname: Groenendijk
authors.forename: Beerend P
authors.initials: BP
authors.lastname: Hierck
authors.forename: Johannes
authors.initials: J
authors.lastname: Vrolijk
authors.forename: Martin
authors.initials: M
authors.lastname: Baiker
authors.forename: Mathieu J B M
authors.initials: MJ
authors.lastname: Pourquie
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Gittenberger-de Groot
authors.forename: Robert E
authors.initials: RE
authors.lastname: Poelmann
mesh_terms: D000818:Animals; D001775:Blood Circulation; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics*; D019332:Endothelin-1 / Q000235:genetics*; D005786:Gene Expression Regulation; D006330:Heart Defects, Congenital / Q000209:etiology*; D017403:In Situ Hybridization; D051741:Kruppel-Like Transcription Factors; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000235:genetics*; D013314:Stress, Mechanical; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D019332:Endothelin-1; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III