title: Disturbed Laminar Blood Flow Vastly Augments Lipoprotein Retention in the Artery Wall: A Key Mechanism Distinguishing Susceptible From Resistant Sites.
abstract: OBJECTIVE
  Atherosclerosis develops initially at branch points and in areas of high vessel curvature. Moreover, experiments in hypercholesterolemic mice have shown that the introduction of disturbed flow in straight, atherosclerosis-resistant arterial segments turns them highly atherosclerosis susceptible. Several biomechanical mechanisms have been proposed, but none has been demonstrated. In the present study, we examined whether a causal link exists between disturbed laminar flow and the ability of the arterial wall to retain lipoproteins.
  
  
  RESULTS
  Lipoprotein retention was detected at natural predilection sites of the murine thoracic aorta 18 hours after infusion of fluorescently labeled low-density lipoprotein. To test for causality between blood flow and the ability of these areas to retain lipoproteins, we manipulated blood flow in the straight segment of the common carotid artery using a constrictive collar. Disturbed laminar flow did not affect low-density lipoprotein influx, but increased the ability of the artery wall to bind low-density lipoprotein. Concordantly, disturbed laminar flow led to differential expression of genes associated with phenotypic modulation of vascular smooth muscle cells, increased expression of proteoglycan core proteins associated with lipoprotein retention, and of enzymes responsible for chondroitin sulfate glycosaminoglycan synthesis and sulfation.
  
  
  CONCLUSIONS
  Blood flow regulates genes associated with vascular smooth muscle cell phenotypic modulation, as well as the expression and post-translational modification of lipoprotein-binding proteoglycan core proteins, and the introduction of disturbed laminar flow vastly augments the ability of a previously resistant, straight arterial segment to retain lipoproteins.
authors.affiliation: From the Department of Cardiology, and Institute of Clinical Medicine, Aarhus University Hospital, Skejby, Denmark (L.B.S., M.B.M., M.K., M.K.H., J.F.B.); Department of Molecular Biology and Genetics (L.B.S., C.O.) and Department of Biomedicine (M.K.), Aarhus University, Aarhus, Denmark; and Department of Molecular Biology and Genetics (L.B.S., C.O.) and DANDRITE and Danish Diabetes Academy, Department of Biomedicine (M.K.), Aarhus University, Denmark.
authors.forename: Lasse Bach
authors.initials: LB
authors.lastname: Steffensen
authors.affiliation: From the Department of Cardiology, and Institute of Clinical Medicine, Aarhus University Hospital, Skejby, Denmark (L.B.S., M.B.M., M.K., M.K.H., J.F.B.); Department of Molecular Biology and Genetics (L.B.S., C.O.) and Department of Biomedicine (M.K.), Aarhus University, Aarhus, Denmark; and Department of Molecular Biology and Genetics (L.B.S., C.O.) and DANDRITE and Danish Diabetes Academy, Department of Biomedicine (M.K.), Aarhus University, Denmark.
authors.forename: Martin Bødtker
authors.initials: MB
authors.lastname: Mortensen
authors.affiliation: From the Department of Cardiology, and Institute of Clinical Medicine, Aarhus University Hospital, Skejby, Denmark (L.B.S., M.B.M., M.K., M.K.H., J.F.B.); Department of Molecular Biology and Genetics (L.B.S., C.O.) and Department of Biomedicine (M.K.), Aarhus University, Aarhus, Denmark; and Department of Molecular Biology and Genetics (L.B.S., C.O.) and DANDRITE and Danish Diabetes Academy, Department of Biomedicine (M.K.), Aarhus University, Denmark.
authors.forename: Mads
authors.initials: M
authors.lastname: Kjolby
authors.affiliation: From the Department of Cardiology, and Institute of Clinical Medicine, Aarhus University Hospital, Skejby, Denmark (L.B.S., M.B.M., M.K., M.K.H., J.F.B.); Department of Molecular Biology and Genetics (L.B.S., C.O.) and Department of Biomedicine (M.K.), Aarhus University, Aarhus, Denmark; and Department of Molecular Biology and Genetics (L.B.S., C.O.) and DANDRITE and Danish Diabetes Academy, Department of Biomedicine (M.K.), Aarhus University, Denmark.
authors.forename: Mette Kallestrup
authors.initials: MK
authors.lastname: Hagensen
authors.affiliation: From the Department of Cardiology, and Institute of Clinical Medicine, Aarhus University Hospital, Skejby, Denmark (L.B.S., M.B.M., M.K., M.K.H., J.F.B.); Department of Molecular Biology and Genetics (L.B.S., C.O.) and Department of Biomedicine (M.K.), Aarhus University, Aarhus, Denmark; and Department of Molecular Biology and Genetics (L.B.S., C.O.) and DANDRITE and Danish Diabetes Academy, Department of Biomedicine (M.K.), Aarhus University, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Oxvig
authors.affiliation: From the Department of Cardiology, and Institute of Clinical Medicine, Aarhus University Hospital, Skejby, Denmark (L.B.S., M.B.M., M.K., M.K.H., J.F.B.); Department of Molecular Biology and Genetics (L.B.S., C.O.) and Department of Biomedicine (M.K.), Aarhus University, Aarhus, Denmark; and Department of Molecular Biology and Genetics (L.B.S., C.O.) and DANDRITE and Danish Diabetes Academy, Department of Biomedicine (M.K.), Aarhus University, Denmark. jben@clin.au.dk.
authors.forename: Jacob Fog
authors.initials: JF
authors.lastname: Bentzon
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D008074:Lipoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D012039:Regional Blood Flow / Q000502:physiology*
chemical_list: D008074:Lipoproteins
keywords: atherosclerosis; carotid artery; lipoproteins; mice; proteoglycans