title: Endothelial primary cilia inhibit atherosclerosis.
abstract: Primary cilia are microtubule-based structures present on most mammalian cells that are important for intercellular signaling. Cilia are present on a subset of endothelial cells where they project into the vessel lumen and are implicated as mechanical sensors of blood flow. To test the in vivo role of endothelial cilia, we conditionally deleted Ift88, a gene required for ciliogenesis, in endothelial cells of mice. We found that endothelial primary cilia were dispensable for mammalian vascular development. Cilia were not uniformly distributed in the mouse aorta, but were enriched at vascular branch points and sites of high curvature. These same sites are predisposed to the development of atherosclerotic plaques, prompting us to investigate whether cilia participate in atherosclerosis. Removing endothelial cilia increased atherosclerosis in Apoe(-/-) mice fed a high-fat, high-cholesterol diet, indicating that cilia protect against atherosclerosis. Removing endothelial cilia increased inflammatory gene expression and decreased eNOS activity, indicating that endothelial cilia inhibit pro-atherosclerotic signaling in the aorta.
authors.affiliation: Department of Biochemistry and Biophysics, Cardiovascular Research Institute University of California, San Francisco San Francisco, CA, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Dinsmore
authors.affiliation: Department of Biochemistry and Biophysics, Cardiovascular Research Institute University of California, San Francisco San Francisco, CA, USA jeremy.reiter@ucsf.edu.
authors.forename: Jeremy F
authors.initials: JF
authors.lastname: Reiter
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002923:Cilia / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D008297:Male; D051379:Mice; D058226:Plaque, Atherosclerotic / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; C490898:Tg737Rpw protein, mouse; D025521:Tumor Suppressor Proteins