Effects of transmural pressure and wall shear stress on LDL accumulation in the arterial wall: a numerical study using a multilayered model
1 Department of Chemical Engineering and 2 National Heart and Lung Institute, International Centre for Circulatory Health, Imperial College London, London, United Kingdom Submitted 22 November 2006 ; accepted in final form 31 January 2007 The accumulation of low-density lipoprotein (LDL) is recogniz...
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container_title | American journal of physiology. Heart and circulatory physiology |
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creator | Sun, Nanfeng Wood, Nigel B Hughes, Alun D Thom, Simon A. M Yun Xu, X |
description | 1 Department of Chemical Engineering and 2 National Heart and Lung Institute, International Centre for Circulatory Health, Imperial College London, London, United Kingdom
Submitted 22 November 2006
; accepted in final form 31 January 2007
The accumulation of low-density lipoprotein (LDL) is recognized as one of the main contributors in atherogenesis. Mathematical models have been constructed to simulate mass transport in large arteries and the consequent lipid accumulation in the arterial wall. The objective of this study was to investigate the influences of wall shear stress and transmural pressure on LDL accumulation in the arterial wall by a multilayered, coupled lumen-wall model. The model employs the Navier-Stokes equations and Darcy's Law for fluid dynamics, convection-diffusion-reaction equations for mass balance, and Kedem-Katchalsky equations for interfacial coupling. To determine physiologically realistic model parameters, an optimization approach that searches optimal parameters based on experimental data was developed. Two sets of model parameters corresponding to different transmural pressures were found by the optimization approach using experimental data in the literature. Furthermore, a shear-dependent hydraulic conductivity relation reported previously was adopted. The integrated multilayered model was applied to an axisymmetric stenosis simulating an idealized, mildly stenosed coronary artery. The results show that low wall shear stress leads to focal LDL accumulation by weakening the convective clearance effect of transmural flow, whereas high transmural pressure, associated with hypertension, leads to global elevation of LDL concentration in the arterial wall by facilitating the passage of LDL through wall layers.
low-desity lipoprotein transport; lipid accumulation; atherosclerosis; hypertension
Address for reprint requests and other correspondence: N. Sun, Dept. of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK (e-mail: nanfeng.sun{at}imperial.ac.uk ) |
doi_str_mv | 10.1152/ajpheart.01281.2006 |
format | Article |
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Submitted 22 November 2006
; accepted in final form 31 January 2007
The accumulation of low-density lipoprotein (LDL) is recognized as one of the main contributors in atherogenesis. Mathematical models have been constructed to simulate mass transport in large arteries and the consequent lipid accumulation in the arterial wall. The objective of this study was to investigate the influences of wall shear stress and transmural pressure on LDL accumulation in the arterial wall by a multilayered, coupled lumen-wall model. The model employs the Navier-Stokes equations and Darcy's Law for fluid dynamics, convection-diffusion-reaction equations for mass balance, and Kedem-Katchalsky equations for interfacial coupling. To determine physiologically realistic model parameters, an optimization approach that searches optimal parameters based on experimental data was developed. Two sets of model parameters corresponding to different transmural pressures were found by the optimization approach using experimental data in the literature. Furthermore, a shear-dependent hydraulic conductivity relation reported previously was adopted. The integrated multilayered model was applied to an axisymmetric stenosis simulating an idealized, mildly stenosed coronary artery. The results show that low wall shear stress leads to focal LDL accumulation by weakening the convective clearance effect of transmural flow, whereas high transmural pressure, associated with hypertension, leads to global elevation of LDL concentration in the arterial wall by facilitating the passage of LDL through wall layers.
low-desity lipoprotein transport; lipid accumulation; atherosclerosis; hypertension
Address for reprint requests and other correspondence: N. Sun, Dept. of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK (e-mail: nanfeng.sun{at}imperial.ac.uk )</description><identifier>ISSN: 0363-6135</identifier><identifier>EISSN: 1522-1539</identifier><identifier>DOI: 10.1152/ajpheart.01281.2006</identifier><identifier>PMID: 17277019</identifier><identifier>CODEN: AJPPDI</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>Animals ; Atherosclerosis - metabolism ; Atherosclerosis - pathology ; Atherosclerosis - physiopathology ; Blood Pressure ; Computer Simulation ; Coronary Stenosis - metabolism ; Coronary Stenosis - pathology ; Coronary Stenosis - physiopathology ; Coronary Vessels - metabolism ; Coronary Vessels - pathology ; Coronary Vessels - physiopathology ; Humans ; Hypertension ; Hypertension - metabolism ; Hypertension - pathology ; Hypertension - physiopathology ; Lipoproteins, LDL - metabolism ; Low density lipoprotein ; Mathematical models ; Models, Cardiovascular ; Severity of Illness Index ; Shear stress ; Stress, Mechanical ; Veins & arteries</subject><ispartof>American journal of physiology. Heart and circulatory physiology, 2007-06, Vol.292 (6), p.H3148-H3157</ispartof><rights>Copyright American Physiological Society Jun 2007</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c488t-24921a1704a2b0349c6bcc309831d4c0d10444321eeeae62ea12993fa3adf4f03</citedby><cites>FETCH-LOGICAL-c488t-24921a1704a2b0349c6bcc309831d4c0d10444321eeeae62ea12993fa3adf4f03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3025,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17277019$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sun, Nanfeng</creatorcontrib><creatorcontrib>Wood, Nigel B</creatorcontrib><creatorcontrib>Hughes, Alun D</creatorcontrib><creatorcontrib>Thom, Simon A. M</creatorcontrib><creatorcontrib>Yun Xu, X</creatorcontrib><title>Effects of transmural pressure and wall shear stress on LDL accumulation in the arterial wall: a numerical study using a multilayered model</title><title>American journal of physiology. Heart and circulatory physiology</title><addtitle>Am J Physiol Heart Circ Physiol</addtitle><description>1 Department of Chemical Engineering and 2 National Heart and Lung Institute, International Centre for Circulatory Health, Imperial College London, London, United Kingdom
Submitted 22 November 2006
; accepted in final form 31 January 2007
The accumulation of low-density lipoprotein (LDL) is recognized as one of the main contributors in atherogenesis. Mathematical models have been constructed to simulate mass transport in large arteries and the consequent lipid accumulation in the arterial wall. The objective of this study was to investigate the influences of wall shear stress and transmural pressure on LDL accumulation in the arterial wall by a multilayered, coupled lumen-wall model. The model employs the Navier-Stokes equations and Darcy's Law for fluid dynamics, convection-diffusion-reaction equations for mass balance, and Kedem-Katchalsky equations for interfacial coupling. To determine physiologically realistic model parameters, an optimization approach that searches optimal parameters based on experimental data was developed. Two sets of model parameters corresponding to different transmural pressures were found by the optimization approach using experimental data in the literature. Furthermore, a shear-dependent hydraulic conductivity relation reported previously was adopted. The integrated multilayered model was applied to an axisymmetric stenosis simulating an idealized, mildly stenosed coronary artery. The results show that low wall shear stress leads to focal LDL accumulation by weakening the convective clearance effect of transmural flow, whereas high transmural pressure, associated with hypertension, leads to global elevation of LDL concentration in the arterial wall by facilitating the passage of LDL through wall layers.
low-desity lipoprotein transport; lipid accumulation; atherosclerosis; hypertension
Address for reprint requests and other correspondence: N. Sun, Dept. of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK (e-mail: nanfeng.sun{at}imperial.ac.uk )</description><subject>Animals</subject><subject>Atherosclerosis - metabolism</subject><subject>Atherosclerosis - pathology</subject><subject>Atherosclerosis - physiopathology</subject><subject>Blood Pressure</subject><subject>Computer Simulation</subject><subject>Coronary Stenosis - metabolism</subject><subject>Coronary Stenosis - pathology</subject><subject>Coronary Stenosis - physiopathology</subject><subject>Coronary Vessels - metabolism</subject><subject>Coronary Vessels - pathology</subject><subject>Coronary Vessels - physiopathology</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Hypertension - metabolism</subject><subject>Hypertension - pathology</subject><subject>Hypertension - physiopathology</subject><subject>Lipoproteins, LDL - metabolism</subject><subject>Low density lipoprotein</subject><subject>Mathematical models</subject><subject>Models, Cardiovascular</subject><subject>Severity of Illness Index</subject><subject>Shear stress</subject><subject>Stress, Mechanical</subject><subject>Veins & arteries</subject><issn>0363-6135</issn><issn>1522-1539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kUuLFDEUhYMoTjv6CwQJLtx1T171iK6GcR5Cg5txHdKpW11pUg_zYKzf4J82ZbczIrgKnHu-k8s9CL2lZENpwS70YepA-7ghlNV0wwgpn6FVnrA1Lbh8jlaEl3xdUl6coVchHAghRVXyl-iMVqyqCJUr9PO6bcHEgMcWR6-H0CevHZ48hJA8YD00-EE7h8PyFw5xGeBxwNvPW6yNSX1yOtos2AHHLgM-grc5YqE-Yo2H1GfBZCXE1Mw4BTvss57BaJ2ewUOD-7EB9xq9aLUL8Ob0nqNvN9f3V3fr7dfbL1eX27URdR3XTEhGNa2I0GxHuJCm3BnDiaw5bYQhDSVCCM4oAGgoGWjKpOSt5rppRUv4OfpwzJ38-D1BiKq3wYBzeoAxBVWRQjJe1Nn4_h_jYUx-yLspxmSZ785FNvGjyfgxBA-tmrzttZ8VJWopSv0pSv0uSi1FZerdKTrtemiemFMz2fDpaOjsvnuwHtTUzcGObtzP6iY5dw8_4mM0k0yV6o5TUaupaTN98X_6cZ-_KP4Lzz24vg</recordid><startdate>20070601</startdate><enddate>20070601</enddate><creator>Sun, Nanfeng</creator><creator>Wood, Nigel B</creator><creator>Hughes, Alun D</creator><creator>Thom, Simon A. 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M ; Yun Xu, X</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c488t-24921a1704a2b0349c6bcc309831d4c0d10444321eeeae62ea12993fa3adf4f03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Atherosclerosis - metabolism</topic><topic>Atherosclerosis - pathology</topic><topic>Atherosclerosis - physiopathology</topic><topic>Blood Pressure</topic><topic>Computer Simulation</topic><topic>Coronary Stenosis - metabolism</topic><topic>Coronary Stenosis - pathology</topic><topic>Coronary Stenosis - physiopathology</topic><topic>Coronary Vessels - metabolism</topic><topic>Coronary Vessels - pathology</topic><topic>Coronary Vessels - physiopathology</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Hypertension - metabolism</topic><topic>Hypertension - pathology</topic><topic>Hypertension - physiopathology</topic><topic>Lipoproteins, LDL - metabolism</topic><topic>Low density lipoprotein</topic><topic>Mathematical models</topic><topic>Models, Cardiovascular</topic><topic>Severity of Illness Index</topic><topic>Shear stress</topic><topic>Stress, Mechanical</topic><topic>Veins & arteries</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Nanfeng</creatorcontrib><creatorcontrib>Wood, Nigel B</creatorcontrib><creatorcontrib>Hughes, Alun D</creatorcontrib><creatorcontrib>Thom, Simon A. 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Heart and circulatory physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Nanfeng</au><au>Wood, Nigel B</au><au>Hughes, Alun D</au><au>Thom, Simon A. M</au><au>Yun Xu, X</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of transmural pressure and wall shear stress on LDL accumulation in the arterial wall: a numerical study using a multilayered model</atitle><jtitle>American journal of physiology. Heart and circulatory physiology</jtitle><addtitle>Am J Physiol Heart Circ Physiol</addtitle><date>2007-06-01</date><risdate>2007</risdate><volume>292</volume><issue>6</issue><spage>H3148</spage><epage>H3157</epage><pages>H3148-H3157</pages><issn>0363-6135</issn><eissn>1522-1539</eissn><coden>AJPPDI</coden><abstract>1 Department of Chemical Engineering and 2 National Heart and Lung Institute, International Centre for Circulatory Health, Imperial College London, London, United Kingdom
Submitted 22 November 2006
; accepted in final form 31 January 2007
The accumulation of low-density lipoprotein (LDL) is recognized as one of the main contributors in atherogenesis. Mathematical models have been constructed to simulate mass transport in large arteries and the consequent lipid accumulation in the arterial wall. The objective of this study was to investigate the influences of wall shear stress and transmural pressure on LDL accumulation in the arterial wall by a multilayered, coupled lumen-wall model. The model employs the Navier-Stokes equations and Darcy's Law for fluid dynamics, convection-diffusion-reaction equations for mass balance, and Kedem-Katchalsky equations for interfacial coupling. To determine physiologically realistic model parameters, an optimization approach that searches optimal parameters based on experimental data was developed. Two sets of model parameters corresponding to different transmural pressures were found by the optimization approach using experimental data in the literature. Furthermore, a shear-dependent hydraulic conductivity relation reported previously was adopted. The integrated multilayered model was applied to an axisymmetric stenosis simulating an idealized, mildly stenosed coronary artery. The results show that low wall shear stress leads to focal LDL accumulation by weakening the convective clearance effect of transmural flow, whereas high transmural pressure, associated with hypertension, leads to global elevation of LDL concentration in the arterial wall by facilitating the passage of LDL through wall layers.
low-desity lipoprotein transport; lipid accumulation; atherosclerosis; hypertension
Address for reprint requests and other correspondence: N. Sun, Dept. of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK (e-mail: nanfeng.sun{at}imperial.ac.uk )</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>17277019</pmid><doi>10.1152/ajpheart.01281.2006</doi></addata></record> |
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source | MEDLINE; American Physiological Society; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
subjects | Animals Atherosclerosis - metabolism Atherosclerosis - pathology Atherosclerosis - physiopathology Blood Pressure Computer Simulation Coronary Stenosis - metabolism Coronary Stenosis - pathology Coronary Stenosis - physiopathology Coronary Vessels - metabolism Coronary Vessels - pathology Coronary Vessels - physiopathology Humans Hypertension Hypertension - metabolism Hypertension - pathology Hypertension - physiopathology Lipoproteins, LDL - metabolism Low density lipoprotein Mathematical models Models, Cardiovascular Severity of Illness Index Shear stress Stress, Mechanical Veins & arteries |
title | Effects of transmural pressure and wall shear stress on LDL accumulation in the arterial wall: a numerical study using a multilayered model |
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