title: Primary cilia sensitize endothelial cells for fluid shear stress.
abstract: Primary cilia are mechanosensors for fluid shear stress, and are involved in a number of syndromes and congenital anomalies. We identified endothelial cilia in areas of low shear stress in the embryonic heart. The objective of the present study was to demonstrate the role of primary cilia in mechanosensing. Ciliated embryonic endothelial cells were cultured from the heart, and non-ciliated cells from the arteries. Non-ciliated cells that were subjected to fluid shear stress showed significantly less induction of the shear marker Krüppel-Like Factor-2, as compared to ciliated cells. In addition, ciliated cells from which the cilia were chemically removed show a similar decrease in flow response. This shows that primary cilia sensitize endothelial cells for fluid shear stress. In addition, we targeted and stabilized the connection of the cilium to the cytoplasm by treatment with Colchicine and Taxol/Paclitaxel, respectively, and show that microtubular integrity is essential to sense shear stress.
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands. B.P.Hierck@LUMC.nl
authors.forename: Beerend P
authors.initials: BP
authors.lastname: Hierck
authors.forename: Kim
authors.initials: K
authors.lastname: Van der Heiden
authors.forename: Fanneke E
authors.initials: FE
authors.lastname: Alkemade
authors.forename: Simone
authors.initials: S
authors.lastname: Van de Pas
authors.forename: Johannes V
authors.initials: JV
authors.lastname: Van Thienen
authors.forename: Bianca C W
authors.initials: BC
authors.lastname: Groenendijk
authors.forename: Wilhelmina H
authors.initials: WH
authors.lastname: Bax
authors.forename: Arnoud
authors.initials: A
authors.lastname: Van der Laarse
authors.forename: Marco C
authors.initials: MC
authors.lastname: Deruiter
authors.forename: Anton J G
authors.initials: AJ
authors.lastname: Horrevoets
authors.forename: Robert E
authors.initials: RE
authors.lastname: Poelmann
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D002923:Cilia / Q000187:drug effects / Q000502:physiology*; D003370:Coturnix; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006321:Heart / Q000187:drug effects / Q000196:embryology*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008870:Microtubules / Q000502:physiology; D009206:Myocardium / Q000166:cytology*; D017239:Paclitaxel / Q000494:pharmacology; D013314:Stress, Mechanical; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D051741:Kruppel-Like Transcription Factors; D050257:Tubulin Modulators; D017239:Paclitaxel