title: Endothelial primary cilia in areas of disturbed flow are at the base of atherosclerosis.
abstract: Atherosclerosis develops in the arterial system at sites of low as well as low and oscillating shear stress. Previously, we demonstrated a shear-related distribution of ciliated endothelial cells in the embryonic cardiovascular system and postulated that the primary cilium is a component of the shear stress sensor, functioning as a signal amplifier. This shear-related distribution is reminiscent of the atherosclerotic predilection sites. Thus, we determined whether a link exists between location and frequency of endothelial primary cilia and atherogenesis. We analyzed endothelial ciliation of the adult aortic arch and common carotid arteries of wild type C57BL/6 and apolipoprotein-E-deficient mice. Primary cilia are located at the atherosclerotic predilection sites, where flow is disturbed, in wild type mice and they occur on and around atherosclerotic lesions in apolipoprotein-E-deficient mice, which have significantly more primary cilia in the aortic arch than wild type mice. In addition, common carotid arteries were challenged for shear stress by application of a restrictive cast, resulting in the presence of primary cilia only at sites of induced low and disturbed shear. In conclusion, these data relate the presence of endothelial primary cilia to regions of atherogenesis, where they increase in number under hyperlipidemia-induced lesion formation. Experimentally induced flow disturbance leads to induction of primary cilia, and subsequently to atherogenesis, which suggests a role for primary cilia in endothelial activation and dysfunction.
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Kim
authors.initials: K
authors.lastname: Van der Heiden
authors.forename: Beerend P
authors.initials: BP
authors.lastname: Hierck
authors.forename: Rob
authors.initials: R
authors.lastname: Krams
authors.forename: Rini
authors.initials: R
authors.lastname: de Crom
authors.forename: Caroline
authors.initials: C
authors.lastname: Cheng
authors.forename: Martin
authors.initials: M
authors.lastname: Baiker
authors.forename: Mathieu J B M
authors.initials: MJ
authors.lastname: Pourquie
authors.forename: Fanneke E
authors.initials: FE
authors.lastname: Alkemade
authors.forename: Marco C
authors.initials: MC
authors.lastname: DeRuiter
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; D001013:Aorta, Thoracic / Q000648:ultrastructure; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000473:pathology*; D001783:Blood Flow Velocity; D002339:Carotid Arteries / Q000473:pathology / Q000648:ultrastructure; D002923:Cilia / Q000473:pathology*; D004727:Endothelium / Q000648:ultrastructure*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013314:Stress, Mechanical
chemical_list: D001057:Apolipoproteins E