The transport of macromolecules, such as low density lipoproteins (LDLs), across the artery wall and their accumulation in the wall is a key step in atherogenesis. Our objective was to model fluid flow within both the lumen and wall of a constricted, axisymmetric tube simulating a stenosed artery, and to then use this flow pattern to study LDL mass transport from the blood to the artery wall. Coupled analysis of lumenal blood flow and transmural fluid flow was achieved through the solution of Brinkman’s model, which is an extension of the Navier-Stokes equations for porous media. This coupled approach offers advantages over traditional analyses of this problem, which have used possibly unrealistic boundary conditions at the blood-wall interface; instead, we prescribe a more natural pressure boundary condition at the adventitial vasa vasorum, and allow variations in wall permeability due to the occurrence of plaque. Numerical complications due to the convection dominated mass transport process (low LDL diffusivity) are handled by the streamline upwind/Petrov-Galerkin (SUPG) finite element method. This new fluid-plus-porous-wall method was implemented for conditions typical of LDL transport in a stenosed artery with a 75 percent area reduction (Peclet number=2×108). The results show an elevated LDL concentration at the downstream side of the stenosis. For the higher Darcian wall permeability thought to occur in regions containing atheromatous lesions, this leads to an increased transendothelial LDL flux downstream of the stenosis. Increased transmural filtration in such regions, when coupled with a concentration-dependent endothelial permeability to LDL, could be an important contributor to LDL infiltration into the arterial wall. Experimental work is needed to confirm these results.

1.
Caro
,
C. G.
,
Fitz-Gerald
,
J. M.
, and
Schroter
,
R. C.
,
1971
, “
Atheroma and Arterial Wall Shear. Observation, Correlation and Proposal of a Shear Dependent Mass Transfer Mechanism for Atherogenesis
,”
Proc. R. Soc. London, Ser. B
,
177
, pp.
109
159
.
2.
Hoff
,
H. F.
,
Heideman
,
C. L.
,
Jackson
,
R. L.
,
Bayardo
,
R. J.
,
Kim
,
H. S.
, and
Gotto
,
A. M.
, Jr.
,
1975
, “
Localization Patterns of Plasma Apolipoproteins in Human Atherosclerotic Lesions
,”
Circ. Res.
,
37
, pp.
72
79
.
3.
Hoff
,
H. F.
,
Titus
,
J. L.
,
Bajardo
,
R. J.
,
Jackson
,
R. L.
,
Gotto
,
A. M.
,
DeBakey
,
M. E.
, and
Lie
,
J. T.
,
1975
, “
Lipoproteins in Atherosclerotic Lesions. Localization by Immunofluorescence of Apo-Low Density Lipoproteins in Human Atherosclerotic Arteries From Normal and Hyperlipoproteinemics
,”
Arch. Pathol.
,
99
, pp.
253
258
.
4.
Andre
,
P.
,
Baldit
,
S. C.
,
Bonneau
,
M.
,
Pignaud
,
G.
,
Hainaud
,
P.
,
Azzam
,
K.
, and
Drouet
,
L.
,
1996
, “
Which Experimental Model to Choose to Study Arterial Thrombosis and Evaluate Potentially Useful Therapeutics?
,”
Haemostasis
,
26
Suppl 4, pp.
55
69
.
5.
Scott, R. F., Daoud, A. S., and Florentin, R. A., 1972, “Animal Models in Atherosclerosis,” The Pathogenesis of Atherosclerosis, R. W. Wissler and J. C. Geer, eds., The Williams and Wilkins Company, Baltimore.
6.
Huang
,
Z. J.
, and
Tarbell
,
J. M.
,
1997
, “
Numerical Simulation of Mass Transfer in Porous Media of Blood Vessel Walls
,”
Am. J. Phys.
,
273
, pp.
H464–H477
H464–H477
.
7.
Kim
,
W. S.
, and
Tarbell
,
J. M.
,
1994
, “
Macromolecular Transport Through the Deformable Porous Media of an Artery Wall
,”
ASME J. Biomech. Eng.
,
116
, pp.
156
163
.
8.
Yuan
,
F.
,
Chien
,
S.
, and
Weinbaum
,
S.
,
1991
, “
A New View of Convective-Diffusive Transport Processes in the Arterial Intima
,”
ASME J. Biomech. Eng.
,
113
, pp.
314
329
.
9.
Deng
,
X.
,
Marois
,
Y.
,
How
,
T.
,
Merhi
,
Y.
,
King
,
M.
,
Guidoin
,
R.
, and
Karino
,
T.
,
1995
, “
Luminal Surface Concentration of Lipoprotein (LDL) and Its Effect on the Wall Uptake of Cholesterol by Canine Carotid Arteries
,”
J. Vasc. Surg.
,
21
, pp.
135
145
.
10.
Karmakar
,
N.
, and
Dhar
,
P.
,
1996
, “
Effect of Steady Shear Stress on Fluid Filtration Through the Rabbit Arterial Wall in the Presence of Macromolecules
,”
Clin. Exp. Pharmacol. Physiol.
,
23
, pp.
299
304
.
11.
Rappitsch
,
G.
, and
Perktold
,
K.
,
1996
, “
Computer Simulation of Convective Diffusion Processes in Large Arteries
,”
J. Biomech.
,
29
, pp.
207
215
.
12.
Deng
,
X.
,
King
,
M. W.
, and
Guidoin
,
R.
,
1995
, “
Localization of Atherosclerosis in Arterial Junctions. Concentration Distribution of Low Density Lipoproteins at the Luminal Surface in Regions of Disturbed Flow
,”
ASAIO J.
,
41
, pp.
58
67
.
13.
Ma
,
P.
,
Li
,
X.
, and
Ku
,
D. N.
,
1997
, “
Convective Mass Transfer at the Carotid Bifurcation
,”
J. Biomech.
,
30
, pp.
565
571
.
14.
Rappitsch
,
G.
, and
Perktold
,
K.
,
1996
, “
Pulsatile Albumin Transport in Large Arterics: a Numerical Simulation Study
,”
ASME J. Biomech. Eng.
,
118
, pp.
511
519
.
15.
Karner, G., and Perktold, K., 1999, “Numerical modeling of mass transport in the arterial wall,” V. K. Goel et al., eds., Proceedings, 1999 Bioengincering Conference, BED Vol. 42, ASME Press, New York, pp. 739–740.
16.
Stangeby, D. K., and Ethier, C. R., 2000, “Computational analysis of convection dominated transport in two media: arterial mass transport,” Proceedings, Conference on Mathematical Modeling and Scientific Computing.
17.
Friedman, M. H., 1986, Principles and Models of Biological Transport, Springer-Verlag, Berlin.
18.
Back
,
L. H.
,
1975
, “
Theoretical Investigation of Mass Transport to Arterial Walls in Various Blood Flow Regions—I. Flow Field and Lipoprotein Transport
,”
Math. Biosci.
,
27
, pp.
231
262
.
19.
Tedgui
,
A.
, and
Lever
,
M. J.
,
1984
, “
Filtration Through Damaged and Undamaged Rabbit Thoracic Aorta
,”
Am. J. Phys.
,
247
, pp.
H784–H791
H784–H791
.
20.
Wilens
,
S. L.
, and
McCluskey
,
R. T.
,
1952
, “
The Comparative Filtration Properties of Excised Arteries and Veins
,”
Am. J. Med. Sci.
,
224
, pp.
540
547
.
21.
Probstein, R. F., 1989, Physicochemical Hydrodynamics: an Introduction, Butterworths Publishers, Boston, MA.
22.
Nichols, W. W., and O’Rourke, M. F., 1990, McDonald’s Blood Flow in Arteries, Lea & Febiger, Philadelphia.
23.
Ethier, C. R., Steinman, D. A., and Ojha, M., 1999, “Comparisons between computational hemodynamics, photochromic dye flow visualization and magnetic resonance velocimetry,” Haemodynamics of Arterial Organs. X. Y. Xu and M. W. Collins, eds., WIT Press, Southampton, pp. 131–183.
24.
Friedman
,
M. H.
, and
Ehrlich
,
L. W.
,
1975
, “
Effect of Spatial Variations in Shear on Diffusion at the Wall of an Arterial Branch
,”
Circ. Res.
,
37
, pp.
446
454
.
25.
Truskey
,
G. A.
,
Roberts
,
W. L.
,
Herrmann
,
R. A.
, and
Malinauskas
,
R. A.
,
1992
, “
Measurement of Endothelial Permeability to 1251-Low Density Lipoproteins in Rabbit Arteries by Use of En Face Preparations
,”
Circ. Res.
,
71
, pp.
883
897
.
26.
Schneiderman
,
G.
, and
Goldstick
,
T. K.
,
1978
, “
Significance of Luminal Plasma Layer Resistance in Arterial Wall Oxygen Supply
,”
Atherosclerosis
,
31
, pp.
11
20
.
27.
Tompkins
,
R. G.
,
1991
, “
Quantitative Analysis of Blood Vessel Permeability of Squirrel Monkeys
,”
Am. J. Phys.
,
260
, pp.
H1194–H1204
H1194–H1204
.
28.
Kim
,
A.
,
Wang
,
C. H.
,
Johnson
,
M.
, and
Kamm
,
R.
,
1991
, “
The Specific Hydraulic Conductivity of Bovine Serum Albumin
,”
Biorheology
,
28
, pp.
401
419
.
29.
Laurent
,
T. C.
, and
Pietruszkiewicz
,
A.
,
1961
, “
The effect of hyaluronic acid on the sedimentation rate of other substances
,”
Biochimica et Biophysica Acta
,
49
, pp.
258
264
.
30.
Laurent
,
T. C.
,
Bjork
,
I.
,
Pietruszkiewicz
,
A.
, and
Persson
,
H.
,
1963
, “
On the interaction between polysaccharides and other macromolecules: II. The transport of globular particles through hyaluronic acid solutions
,”
Biochimica et Biophysica Acta
,
78
, pp.
351
359
.
31.
Levick
,
J. R.
,
1987
, “
Flow Through Interstitium and Other Fibrous Matrices
,”
Q. J. Exp. Physiol.
,
72
, pp.
409
437
.
32.
Moore
,
J. A.
, and
Ethier
,
C. R.
,
1997
, “
Oxygen Mass Transfer Calculations in Large Arteries
,”
ASME J. Biomech. Eng.
,
119
, pp.
469
475
.
33.
Guretzki
,
H. J.
,
Gerbitz
,
K. D.
,
Olgemoller
,
B.
, and
Schleicher
,
E.
,
1994
, “
Atherogenic Levels of Low Density Lipoprotein Alter the Permeability and Composition of the Endothelial Barrier
,”
Atherosclerosis
,
107
, pp.
15
24
.
34.
Colton
,
C. K.
,
Friedman
,
S.
,
Wilson
,
D. E.
, and
Lees
,
R. S.
,
1972
, “
Ultrafiltration of Lipoproteins Through a Synthetic Membrane. Implications for the Filtration Theory of Atherogenesis
,”
J. Clin. Invest.
,
51
, pp.
2472
2481
.
35.
Ethier
,
C. R.
,
1991
, “
Flow Through Mixed Fibrous Porous Materials
,”
AIChE J.
,
37
, pp.
1227
1236
.
36.
Neale
,
G.
, and
Nader
,
W.
,
1974
, “
Practical Significance of Brinkman’s Extension of Darcy’s Law: Coupled Parallel Flows Within a Channel and a Bounding Porous Medium
,”
Can. J. Chem. Eng.
,
52
, pp.
475
478
.
37.
Wang
,
D. M.
, and
Tarbell
,
J. M.
,
1995
, “
Modeling Interstitial Flow in an Artery Wall Allows Estimation of Wall Shear Stress on Smooth Muscle Cells
,”
ASME J. Biomech. Eng.
,
117
, pp.
358
363
.
38.
Wada, S., and Karino, T., 1999, “Relationship between wall shear stress and surface concentration of lipoproteins calculated for a multiple bend of the human right coronary artery,” V. K. Goel et al., eds., Proceedings, 1999 Bioengineering Conference, BED Vol. 42, ASME Press, New York, pp. 735–736.
39.
Whale
,
M. D.
,
Grodzinsky
,
A. J.
, and
Johnson
,
M.
,
1996
, “
The Effect of Aging and Pressure on the Specific Hydraulic Conductivity of the Aortic Wall
,”
Biorheology
,
33
, pp.
17
44
.
40.
Curmi
,
P. A.
,
Juan
,
L.
, and
Tedgui
,
A.
,
1990
, “
Effect of Transmural Pressure on Low Density Lipoprotein and Albumin Transport and Distribution Across the Intact Arterial Wall
,”
Circ. Res.
,
66
, pp.
1692
1702
.
41.
Goldstein
,
J. L.
, and
Brown
,
M. S.
,
1977
, “
The Low-Density Lipoprotein Pathway and Its Relation to Atherosclerosis
,”
Annu. Rev. Biochem.
,
46
, pp.
897
930
.
42.
McIntire
,
L. V.
,
Wagner
,
J. E.
,
Papadaki
,
M.
,
Whitson
,
P. A.
, and
Eskin
,
S. G.
,
1998
, “
Effect of Flow on Gene Regulation in Smooth Muscle Cells and Macromolecular Transport Across Endothelial Cell Monolayers
,”
Biol. Bull.
,
194
, pp.
394
399
.
43.
Phelps
,
J. E.
, and
DePaola
,
N.
,
2000
, “
Spatial Variations in Endothelial Barrier Function in Disturbed Flows in Vitro
,”
American Journal of Physiology: Heart Circulatory Physiology
,
278
, pp.
H469–H476
H469–H476
.
44.
Jo
,
H.
,
Dull
,
R. O.
,
Hollis
,
T. M.
, and
Tarbell
,
J. M.
,
1991
, “
Endothelial Albumin Permeability Is Shear Dependent, Time Dependent, and Reversible
,”
Am. J. Phys.
,
260
, pp.
H1992–H1996
H1992–H1996
.
45.
Sprague
,
E. A.
,
Steinbach
,
B. L.
,
Nerem
,
R. M.
, and
Schwartz
,
C. J.
,
1987
, “
Influence of a Laminar Steady-State Fluid-Imposed Wall Shear Stress on the Binding, Internalization, and Degradation of Low-Density Lipoproteins by Cultured Arterial Endothelium
,”
Circulation
,
76
, pp.
648
656
.
46.
Herman
,
I. M.
,
Brant
,
A. M.
,
Warty
,
V. S.
,
Bonaccorso
,
J.
,
Klein
,
E. C.
,
Kormos
,
R. L.
, and
Borovetz
,
H. S.
,
1987
, “
Hemodynamics and the Vascular Endothelial Cytoskeleton
,”
J. Cell Biol.
,
105
, pp.
291
302
.
47.
Mandarino
,
W. A.
,
Berceli
,
S. A.
,
Sheppeck
,
R. A.
, and
Borovetz
,
H. S.
,
1992
, “
Experimental Determination of Velocity Profiles and Wall Shear Rate Along the Rabbit Aortoiliac Bifurcation: Relationship to Vessel Wall Low-Density Lipoprotein (LDL) Metabolism
,”
J. Biomech.
,
25
, pp.
985
993
.
48.
Neumann
,
S. J.
,
Berceli
,
S. A.
,
Sevick
,
E. M.
,
Lincoff
,
A. M.
,
Warty
,
V. S.
,
Brant
,
A. M.
,
Herman
,
I. M.
, and
Borovetz
,
H. S.
,
1990
, “
Experimental Determination and Mathematical Model of the Transient Incorporation of Cholesterol in the Arterial Wall
,”
Bull. Math. Biol.
,
52
, pp.
711
732
.
49.
Caro
,
C. G.
,
1973
, “
Transport of 14C-4 Cholesterol Between Intra-Luminal Serum and Artery Wall in Isolated Dog Common Carotid Artery
,”
J. Physiol. (Lond)
,
233
, pp.
37P–38P
37P–38P
.
50.
Caro
,
C. G.
,
1974
, “
Transport of 14C-4-Cholesterol Between Perfusing Serum and Dog Common Carotid Artery: a Shear Dependent Process
,”
Cardiovasc. Res.
,
8
, pp.
194
203
.
51.
Caro
,
C. G.
, and
Nerem
,
R. M.
,
1973
, “
Transport of 14C-4-Cholesterol Between Serum and Wall in the Perfused Dog Common Carotid Artery
,”
Cardiovasc. Res.
,
32
, pp.
187
205
.
52.
Baldwin
,
A. L.
,
Wilson
,
L. M.
,
Gradus-Pizlo
,
I.
,
Wilensky
,
R.
, and
March
,
K.
,
1997
, “
Effect of Atherosclerosis on Transmural Convection an Arterial Ultrastructure. Implications for Local Intravascular Drug Delivery
,”
Arterioscler., Thromb., Vasc. Biol.
,
17
, pp.
3365
3375
.
53.
Steinman
,
D. A.
,
Vinh
,
B.
,
Ethier
,
C. R.
,
Ojha
,
M.
,
Cobbold
,
R. S.
, and
Johnston
,
K. W.
,
1993
, “
A Numerical Simulation of Flow in a Two-Dimensional End-to-Side Anastomosis Model
,”
ASME J. Biomech. Eng.
,
115
, pp.
112
118
.
54.
Steinman, D. A., 1993, “Numerical Analysis of Flow in a 2-D Distensible Model of an End-to-Side Anastomosis,” Ph.D. thesis, University of Toronto.
55.
Brooks
,
A. N.
, and
Hughes
,
T. J. R.
,
1982
, “
Streamline Upwind/Petrov-Galerkin Formulations for Convection Dominated Flows With Particular Emphasis on the Incompressible Navier-Stokes Equations
,”
Comput. Methods Appl. Mech. Eng.
,
32
, pp.
199
259
.
56.
Asakura
,
T.
, and
Karino
,
T.
,
1990
, “
Flow Patterns and Spatial Distribution of Atherosclerotic Lesions in Human Coronary Arteries
,”
Circ. Res.
,
66
, pp.
1045
1066
.
57.
Giddens
,
D. P.
,
Zarins
,
C. K.
, and
Glagov
,
S.
,
1993
, “
The Role of Fluid Mechanics in the Localization and Detection of Atherosclerosis
,”
ASME J. Biomech. Eng.
,
115
, pp.
588
594
.
58.
Zarins
,
C. K.
,
Giddens
,
D. P.
,
Bharadvaj
,
B. K.
,
Sottiurai
,
V. S.
,
Mabon
,
R. F.
, and
Glagov
,
S.
,
1983
, “
Carotid Bifurcation Atherosclerosis. Quantitative Correlation of Plaque Localization With Flow Velocity Profiles and Wall Shear Stress
,”
Circulation Research
,
53
, pp.
502
514
.
59.
Dirksen
,
M. T.
,
van der Wal
,
A. C.
,
van den Berg
,
F. M.
,
van der Loos
,
C. M.
, and
Becker
,
A. E.
,
1998
, “
Distribution of Inflammatory Cells in Atherosclerotic Plaques Relates to the Direction of Flow
,”
Circulation
,
98
, pp.
2000
2003
.
60.
Smedby
,
O.
,
1997
, “
Do Plaques Grow Upstream or Downstream?: an Angiographic Study in the Femoral Artery
,”
Arterioscler., Thromb., Vasc. Biol.
,
17
, pp.
912
918
.
61.
Gown
,
A. M.
,
Tsukada
,
T.
, and
Ross
,
R.
,
1986
, “
Human Atherosclerosis. II. Immunocytochemical Analysis of the Cellular Composition of Human Atherosclerotic Lesions
,”
Am. J. Pathol.
,
125
, pp.
191
207
.
62.
Gan
,
L.
,
Sjogren
,
L. S.
,
Doroudi
,
R.
, and
Jern
,
S.
,
1999
, “
A New Computerized Biomechanical Perfusion Model for Ex Vivo Study of Fluid Mechanical Forces in Intact Conduit Vessels
,”
J. Vasc. Res.
,
36
, pp.
68
78
.
63.
Vorp
,
D. A.
,
Severyn
,
D. A.
,
Steed
,
D. L.
, and
Webster
,
M. W.
,
1996
, “
A Device for the Application of Cyclic Twist and Extension on Perfused Vascular Segments
,”
Am. J. Phys.
,
270
, pp.
H787–H795
H787–H795
.
64.
Labadie
,
R. F.
,
Antaki
,
J. F.
,
Williams
,
J. L.
,
Katyal
,
S.
,
Ligush
,
J.
,
Watkins
,
S. C.
,
Pham
,
S. M.
, and
Borovetz
,
H. S.
,
1996
, “
Pulsatile Perfusion System for Ex Vivo Investigation of Biochemical Pathways in Intact Vascular Tissue
,”
Am. J. Phys.
,
270
, pp.
H760–H768
H760–H768
.
65.
Larson
,
R. E.
, and
Higdon
,
J. J. L.
,
1987
, “
Microscopic Flow Near the Surface of Two-Dimensional Porous Media. Part 2. Transverse Flow
,”
J. Fluid Mech.
,
178
, pp.
119
136
.
66.
Larson
,
R. E.
, and
Higdon
,
J. J. L.
,
1986
, “
Microscopic Flow Near the Surface of Two-Dimensional Porous Media. Part 1. Axial Flow
,”
J. Fluid Mech.
,
166
, pp.
472
472
.
67.
Fatouraec, N., Deng, X., De Champlain, A., and Guidoin, R., 1999, “Numerical simulation of lipid transport through arterial stenoses,” V. K. Goel et al., eds., Proceedings, 1999 Bioengineering Conference, BED Vol. 42, ASME Press, New York, pp. 733–734.
You do not currently have access to this content.