Disturbed Laminar Blood Flow Vastly Augments Lipoprotein Retention in the Artery Wall: A Key Mechanism Distinguishing Susceptible From Resistant Sites

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Disturbed Laminar Blood Flow Vastly Augments Lipoprotein Retention in the Artery Wall : A Key Mechanism Distinguishing Susceptible From Resistant Sites. / Steffensen, Lasse Bach; Mortensen, Martin Bødtker; Kjolby, Mads; Hagensen, Mette Kallestrup; Oxvig, Claus; Bentzon, Jacob Fog.

I: Arteriosclerosis, Thrombosis, and Vascular Biology, Bind 35, 16.07.2015, s. 1928-1935.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{dacb727c98b243e68d827785d45a0de7,
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.APPROACH AND 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.",
author = "Steffensen, {Lasse Bach} and Mortensen, {Martin B{\o}dtker} and Mads Kjolby and Hagensen, {Mette Kallestrup} and Claus Oxvig and Bentzon, {Jacob Fog}",
note = "{\textcopyright} 2015 American Heart Association, Inc.",
year = "2015",
month = jul,
day = "16",
doi = "10.1161/ATVBAHA.115.305874",
language = "English",
volume = "35",
pages = "1928--1935",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "LIPPINCOTT WILLIAMS & WILKINS",

}

RIS

TY - JOUR

T1 - Disturbed Laminar Blood Flow Vastly Augments Lipoprotein Retention in the Artery Wall

T2 - A Key Mechanism Distinguishing Susceptible From Resistant Sites

AU - Steffensen, Lasse Bach

AU - Mortensen, Martin Bødtker

AU - Kjolby, Mads

AU - Hagensen, Mette Kallestrup

AU - Oxvig, Claus

AU - Bentzon, Jacob Fog

N1 - © 2015 American Heart Association, Inc.

PY - 2015/7/16

Y1 - 2015/7/16

N2 - 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.APPROACH AND 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.

AB - 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.APPROACH AND 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.

U2 - 10.1161/ATVBAHA.115.305874

DO - 10.1161/ATVBAHA.115.305874

M3 - Journal article

C2 - 26183617

VL - 35

SP - 1928

EP - 1935

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

ER -