Abstract

Although sedentary behavior (characterized by prolonged sitting without otherwise being active in daily life) is widely regarded as a risk factor for peripheral artery disease (PAD), underlying biomechanical mechanisms remain insufficiently understood. In this study, geometrical models of ten external iliac arteries were reconstructed based on angiographic data acquired from five healthy young subjects resting in supine and sitting (mimicked by side lying with bent legs) positions, respectively, which were further combined with measured blood flow velocity waveforms in the common iliac arteries (with each body posture being maintained for 30 min) to build computational models for simulating intra-arterial hemodynamics. Morphological analyses showed that the external iliac arteries suffered from evident bending deformation upon the switch of body posture from supine to sitting. Measured blood flow velocity waveforms in the sitting position exhibited a marked decrease in mean flow velocity while increase in retrograde flow ratio compared with those in the supine position. Hemodynamic computations further revealed that sitting significantly altered blood flow patterns in the external iliac arteries, leading to a marked enlargement of atheroprone wall regions exposed to low and oscillatory wall shear stress (WSS), and enhanced multidirectional disturbance of WSS that may further impair endothelial function. In summary, our study demonstrates that prolonged sitting induces atheropromoting hemodynamic changes in the external iliac artery due to the combined effects of vascular bending deformation and changes in flow velocity waveform, which may provide important insights for understanding the involvement of biomechanical factors in sedentary behavior-related PAD.

References

1.
Cooke John
,
P.
, and
Meng
,
S.
,
2020
, “
Vascular Regeneration in Peripheral Artery Disease
,”
Aeterioscler. Thromb. Vasc. Biol.
,
40
(
7
), pp.
1627
1634
.10.1161/ATVBAHA.120.312862
2.
Fowkes
,
F. G.
,
Rudan
,
D.
,
Rudan
,
I.
,
Aboyans
,
V.
,
Denenberg
,
J. O.
,
McDermott
,
M. M.
,
Norman
,
P. E.
,
Sampson
,
U. K.
,
Williams
,
L. J.
,
Mensah
,
G. A.
, and
Criqui
,
M. H.
,
2013
, “
Comparison of Global Estimates of Prevalence and Risk Factors for Peripheral Artery Disease in 2000 and 2010: A Systematic Review and Analysis
,”
Lancet
,
382
(
9901
), pp.
1329
1340
.10.1016/S0140-6736(13)61249-0
3.
Selvin
,
E.
, and
Erlinger
,
T. P.
,
2004
, “
Prevalence of and Risk Factors for Peripheral Arterial Disease in the United States: Results From the National Health and Nutrition Examination Survey, 1999-2000
,”
Circulation
,
110
(
6
), pp.
738
743
.10.1161/01.CIR.0000137913.26087.F0
4.
Unkart
,
J. T.
,
Allison
,
M. A.
,
Parada
,
H.
,
Criqui
,
M. H.
,
Qi
,
Q.
,
Diaz
,
K. M.
,
Carlson
,
J. A.
,
Sotres-Alvarez
,
D.
,
Ostfeld
,
R. J.
,
Raij
,
L.
, and
Bellettiere
,
J.
,
2020
, “
Sedentary Time and Peripheral Artery Disease: The Hispanic Community Health Study/Study of Latinos
,”
Am. Heart J.
,
222
, pp.
208
219
.10.1016/j.ahj.2020.02.005
5.
Credeur
,
D. P.
,
Miller
,
S. M.
,
Jones
,
R.
,
Stoner
,
L.
,
Dolbow
,
D. R.
,
Fryer
,
S. M.
,
Stone
,
K.
, and
McCoy
,
S. M.
,
2019
, “
Impact of Prolonged Sitting on Peripheral and Central Vascular Health
,”
Am. J. Cardiol.
,
123
(
2
), pp.
260
266
.10.1016/j.amjcard.2018.10.014
6.
Carter
,
S.
,
Hartman
,
Y.
,
Holder
,
S.
,
Thijssen
,
D. H.
, and
Hopkins
,
N. D.
,
2017
, “
Sedentary Behavior and Cardiovascular Disease Risk: Mediating Mechanisms
,”
Exerc. Sport Sci. Rev.
,
45
(
2
), pp.
80
86
.10.1249/JES.0000000000000106
7.
Restaino
,
R. M.
,
Walsh
,
L. K.
,
Morishima
,
T.
,
Vranish
,
J. R.
,
Martinez-Lemus
,
L. A.
,
Fadel
,
P. J.
, and
Padilla
,
J.
,
2016
, “
Endothelial Dysfunction Following Prolonged Sitting is Mediated by a Reduction in Shear Stress
,”
Am. J. Physiol. Heart Circ. Physiol.
,
310
(
5
), pp.
H648
H653
.10.1152/ajpheart.00943.2015
8.
Thosar
,
S.
,
Johnson
,
B.
,
Johnston
,
J.
, and
Wallace
,
J.
,
2012
, “
Sitting and Endothelial Dysfunction: The Role of Shear Stress
,”
Med. Sci. Mon. Int. Med. J. Exp. Clin. Res.
,
18
(
12
), pp.
RA173
RA180
.10.12659/MSM.883589
9.
Traub
,
O.
, and
Berk
,
B. C.
,
1998
, “
Laminar Shear Stress
,”
Aeterioscler., Thromb., Vasc. Biol.
,
18
(
5
), pp.
677
685
.10.1161/01.ATV.18.5.677
10.
Padilla
,
J.
, and
Fadel
,
P. J.
,
2017
, “
Prolonged Sitting Leg Vasculopathy: Contributing Factors and Clinical Implications
,”
Am. J. Physiol.-Heart Circ. Physiol.
,
313
(
4
), pp.
H722
H728
.10.1152/ajpheart.00326.2017
11.
Amiri
,
F.
,
Virdis
,
A.
,
Neves
,
M. F.
,
Iglarz
,
M.
,
Seidah
,
N. G.
,
Touyz
,
R. M.
,
Reudelhuber
,
T. L.
, and
Schiffrin
,
E. L.
,
2004
, “
Endothelium-Restricted Overexpression of Human Endothelin-1 Causes Vascular Remodeling and Endothelial Dysfunction
,”
Circulation
,
110
(
15
), pp.
2233
2240
.10.1161/01.CIR.0000144462.08345.B9
12.
Li
,
M. W.
,
Mian
,
M. O. R.
,
Barhoumi
,
T.
,
Rehman
,
A.
,
Mann
,
K.
,
Paradis
,
P.
, and
Schiffrin
,
E. L.
,
2013
, “
Endothelin-1 Overexpression Exacerbates Atherosclerosis and Induces Aortic Aneurysms in Apolipoprotein E Knockout Mice
,”
Aeterioscler. Thromb. Vasc. Biol.
,
33
(
10
), pp.
2306
2315
.10.1161/ATVBAHA.113.302028
13.
Walsh
,
L. K.
,
Restaino
,
R. M.
,
Martinez-Lemus
,
L. A.
, and
Padilla
,
J.
,
2017
, “
Prolonged Leg Bending Impairs Endothelial Function in the Popliteal Artery
,”
Physiol. Rep.
,
5
(
20
), p.
e13478
.10.14814/phy2.13478
14.
Restaino
,
R. M.
,
Holwerda
,
S. W.
,
Credeur
,
D. P.
,
Fadel
,
P. J.
, and
Padilla
,
J.
,
2015
, “
Impact of Prolonged Sitting on Lower and Upper Limb Micro- and Macrovascular Dilator Function
,”
Exp. Physiol.
,
100
(
7
), pp.
829
838
.10.1113/EP085238
15.
Li
,
X.
,
Liu
,
X.
,
Li
,
X.
,
Xu
,
L.
,
Chen
,
X.
, and
Liang
,
F.
,
2019
, “
Tortuosity of the Superficial Femoral Artery and Its Influence on Blood Flow Patterns and Risk of Atherosclerosis
,”
Biomech. Model. Mechanobiol.
,
18
(
4
), pp.
883
896
.10.1007/s10237-019-01118-4
16.
Wood
,
N. B.
,
Zhao
,
S. Z.
,
Zambanini
,
A.
,
Jackson
,
M.
,
Gedroyc
,
W.
,
Thom
,
S. A.
,
Hughes
,
A. D.
, and
Xu
,
X. Y.
,
2006
, “
Curvature and Tortuosity of the Superficial Femoral Artery: A Possible Risk Factor for Peripheral Arterial Disease
,”
J. Appl. Physiol. (1985)
,
101
(
5
), pp.
1412
1418
.10.1152/japplphysiol.00051.2006
17.
Smedby
,
Ö.
, and
Bergstrand
,
L.
,
1996
, “
Tortuosity and Atherosclerosis in the Femoral Artery: What is Cause and What is Effect?
,”
Ann. Biomed. Eng.
,
24
(
4
), pp.
474
480
.10.1007/BF02648109
18.
Mohamied
,
Y.
,
Rowland
,
E. M.
,
Bailey
,
E. L.
,
Sherwin
,
S. J.
,
Schwartz
,
M. A.
, and
Weinberg
,
P. D.
,
2015
, “
Change of Direction in the Biomechanics of Atherosclerosis
,”
Ann. Biomed. Eng.
,
43
(
1
), pp.
16
25
.10.1007/s10439-014-1095-4
19.
Peiffer
,
V.
,
Sherwin
,
S. J.
, and
Weinberg
,
P. D.
,
2013
, “
Computation in the Rabbit Aorta of a New Metric—The Transverse Wall Shear Stress—To Quantify the Multidirectional Character of Disturbed Blood Flow
,”
J. Biomech.
,
46
(
15
), pp.
2651
2658
.10.1016/j.jbiomech.2013.08.003
20.
Mohamied
,
Y.
,
Sherwin
,
S. J.
, and
Weinberg
,
P. D.
,
2017
, “
Understanding the Fluid Mechanics Behind Transverse Wall Shear Stress
,”
J. Biomech.
,
50
, pp.
102
109
.10.1016/j.jbiomech.2016.11.035
21.
Peiffer
,
V.
,
Sherwin
,
S. J.
, and
Weinberg
,
P. D.
,
2013
, “
Does Low and Oscillatory Wall Shear Stress Correlate Spatially With Early Atherosclerosis? A Systematic Review
,”
Cardiovasc. Res.
,
99
(
2
), pp.
242
250
.10.1093/cvr/cvt044
22.
Vranish
,
J. R.
,
Young
,
B. E.
,
Kaur
,
J.
,
Patik
,
J. C.
,
Padilla
,
J.
, and
Fadel
,
P. J.
,
2017
, “
Influence of Sex on Microvascular and Macrovascular Responses to Prolonged Sitting
,”
Am. J. Physiol. Heart Circ. Physiol.
,
312
(
4
), pp.
H800
H805
.10.1152/ajpheart.00823.2016
23.
Padilla
,
J.
,
Sheldon
,
R. D.
,
Sitar
,
D. M.
, and
Newcomer
,
S. C.
,
2009
, “
Impact of Acute Exposure to Increased Hydrostatic Pressure and Reduced Shear Rate on Conduit Artery Endothelial Function: A Limb-Specific Response
,”
Am. J. Physiol. Heart Circ. Physiol.
,
297
(
3
), pp.
H1103
H1108
.10.1152/ajpheart.00167.2009
24.
Vranish
,
J. R.
,
Young
,
B. E.
,
Stephens
,
B. Y.
,
Kaur
,
J.
,
Padilla
,
J.
, and
Fadel
,
P. J.
,
2018
, “
Brief Periods of Inactivity Reduce Leg Microvascular, but Not Macrovascular, Function in Healthy Young Men
,”
Exp. Physiol.
,
103
(
10
), pp.
1425
1434
.10.1113/EP086918
25.
Myers
,
J. G.
,
Moore
,
J. A.
,
Ojha
,
M.
,
Johnston
,
K. W.
, and
Ethier
,
C. R.
,
2001
, “
Factors Influencing Blood Flow Patterns in the Human Right Coronary Artery
,”
Ann. Biomed. Eng.
,
29
(
2
), pp.
109
120
10.1114/1.1349703.
26.
Zhou
,
X.
,
Yin
,
L.
,
Xu
,
L.
, and
Liang
,
F.
,
2020
, “
Non-Periodicity of Blood Flow and Its Influence on Wall Shear Stress in the Carotid Artery Bifurcation: An In Vivo Measurement-Based Computational Study
,”
J. Biomech.
,
101
, p.
109617
10.1016/j.jbiomech.2020.109617.
27.
Xu
,
L.
,
Yin
,
L.
,
Liu
,
Y.
, and
Liang
,
F.
,
2020
, “
A Computational Study on the Influence of Aortic Valve Disease on Hemodynamics in Dilated Aorta
,”
Math. Biosci. Eng.
,
17
(
1
), pp.
606
626
10.3934/mbe.2020031.
28.
Cho
,
Y. I.
, and
Kensey
,
K. R.
,
1991
, “
Effects of the Non-Newtonian Viscosity of Blood on Flows in a Diseased Arterial Vessel. Part 1: Steady Flows
,”
Biorheology
,
28
(
3–4
), pp.
241
262
.10.3233/BIR-1991-283-415
29.
Liang
,
F. Y.
,
Takagi
,
S.
,
Himeno
,
R.
, and
Liu
,
H.
,
2009
, “
Biomechanical Characterization of Ventricular–Arterial Coupling During Aging: A Multi-Scale Model Study
,”
J. Biomech.
,
42
(
6
), pp.
692
704
.10.1016/j.jbiomech.2009.01.010
30.
De Nisco
,
G.
,
Zhang
,
P.
,
Calò
,
K.
,
Liu
,
X.
,
Ponzini
,
R.
,
Bignardi
,
C.
,
Rizzo
,
G.
,
Deng
,
X.
,
Gallo
,
D.
, and
Morbiducci
,
U.
,
2018
, “
What is Needed to Make Low-Density Lipoprotein Transport in Human Aorta Computational Models Suitable to Explore Links to Atherosclerosis? Impact of Initial and Inflow Boundary Conditions
,”
J. Biomech.
,
68
, pp.
33
42
.10.1016/j.jbiomech.2017.12.009
31.
Özkan
,
S.
,
Vural
,
B.
,
Çalışkan
,
E.
,
Bodur
,
H.
,
Türköz
,
E.
, and
Vural
,
F.
,
2007
, “
Color Doppler Sonographic Analysis of Uterine and Ovarian Artery Blood Flow in Women With Polycystic Ovary Syndrome
,”
J. Clin. Ultrasound
,
35
(
6
), pp.
305
313
.10.1002/jcu.20358
32.
Hashimoto
,
J.
, and
Ito
,
S.
,
2010
, “
Pulse Pressure Amplification, Arterial Stiffness, and Peripheral Wave Reflection Determine Pulsatile Flow Waveform of the Femoral Artery
,”
Hypertension
,
56
(
5
), pp.
926
933
.10.1161/HYPERTENSIONAHA.110.159368
33.
Schlager
,
O.
,
Zehetmayer
,
S.
,
Seidinger
,
D.
,
van der Loo
,
B.
, and
Koppensteiner
,
R.
,
2014
, “
Wall Shear Stress in the Stented Superficial Femoral Artery in Peripheral Arterial Disease
,”
Atherosclerosis
,
233
(
1
), pp.
76
82
.10.1016/j.atherosclerosis.2013.12.035
34.
Singh
,
J.
,
Brunner
,
G.
,
Morrisett
,
J. D.
,
Ballantyne
,
C. M.
,
Lumsden
,
A. B.
,
Shah
,
D. J.
, and
Decuzzi
,
P.
,
2018
, “
Patient-Specific Flow Descriptors and Normalized Wall Index in Peripheral Artery Disease: A Preliminary Study
,”
Comput. Methods Biomech. Biomed. Eng. Imaging Vis.
,
6
(
2
), pp.
119
127
.10.1080/21681163.2016.1184589
35.
Malek
,
A. M.
,
Alper
,
S. L.
, and
Izumo
,
S.
,
1999
, “
Hemodynamic Shear Stress and Its Role in Atherosclerosis
,”
JAMA
,
282
(
21
), pp.
2035
2042
.10.1001/jama.282.21.2035
36.
Bonert
,
M.
,
Myers
,
J. G.
,
Fremes
,
S.
,
Williams
,
J.
, and
Ethier
,
C. R.
,
2002
, “
A Numerical Study of Blood Flow in Coronary Artery Bypass Graft Side-to-Side Anastomoses
,”
Ann. Biomed. Eng.
,
30
(
5
), pp.
599
611
.10.1114/1.1481052
37.
Morawietz
,
H.
,
Talanow
,
R.
,
Szibor
,
M.
,
Rueckschloss
,
U.
,
Schubert
,
A.
,
Bartling
,
B.
,
Darmer
,
D.
, and
Holtz
,
J.
,
2000
, “
Regulation of the Endothelin System by Shear Stress in Human Endothelial Cells
,”
J. Physiol.
,
525
(
3
), pp.
761
770
.10.1111/j.1469-7793.2000.00761.x
38.
Wang
,
C.
,
Baker
,
B. M.
,
Chen
,
C. S.
, and
Schwartz
,
M. A.
,
2013
, “
Endothelial Cell Sensing of Flow Direction
,”
Aeterioscler. Thromb. Vasc. Biol.
,
33
(
9
), pp.
2130
2136
.10.1161/ATVBAHA.113.301826
39.
Desyatova
,
A.
,
MacTaggart
,
J.
,
Romarowski
,
R.
,
Poulson
,
W.
,
Conti
,
M.
, and
Kamenskiy
,
A.
,
2018
, “
Effect of Aging on Mechanical Stresses, Deformations, and Hemodynamics in Human Femoropopliteal Artery Due to Limb Flexion
,”
Biomech. Model. Mechanobiol.
,
17
(
1
), pp.
181
189
.10.1007/s10237-017-0953-z
40.
Morishima
,
T.
,
Restaino
,
R. M.
,
Walsh
,
L. K.
,
Kanaley
,
J. A.
,
Fadel
,
P. J.
, and
Padilla
,
J.
,
2016
, “
Prolonged Sitting-Induced Leg Endothelial Dysfunction is Prevented by Fidgeting
,”
Am. J. Physiol.-Heart Circ. Physiol.
,
311
(
1
), pp.
H177
H182
.10.1152/ajpheart.00297.2016
41.
Kim
,
Y.-H.
,
Kim
,
J.-E.
,
Ito
,
Y.
,
Shih
,
A.
,
Brott
,
B.
, and
Anayiotos
,
A.
,
2008
, “
Hemodynamic Analysis of a Compliant Femoral Artery Bifurcation Model Using a Fluid Structure Interaction Framework
,”
Ann. Biomed. Eng.
,
36
(
11
), pp.
1753
1763
.10.1007/s10439-008-9558-0
42.
Moradicheghamahi
,
J.
,
Sadeghiseraji
,
J.
, and
Jahangiri
,
M.
,
2019
, “
Numerical Solution of the Pulsatile, non-Newtonian and Turbulent Blood Flow in a Patient Specific Elastic Carotid Artery
,”
Int. J. Mech. Sci.
,
150
, pp.
393
403
.10.1016/j.ijmecsci.2018.10.046
43.
Khan
,
M. O.
,
Valen-Sendstad
,
K.
, and
Steinman
,
D. A.
,
2019
, “
Direct Numerical Simulation of Laminar-Turbulent Transition in a Non-Axisymmetric Stenosis Model for Newtonian vs. Shear-Thinning Non-Newtonian Rheologies
,”
Flow Turbul. Combust.
,
102
(
1
), pp.
43
72
.10.1007/s10494-018-9905-7
44.
Tan
,
F.
,
Soloperto
,
G.
,
Bashford
,
S.
,
Wood
,
N.
,
Thom
,
S.
,
Hughes
,
A.
, and
Xu
,
X.
,
2008
, “
Analysis of Flow Disturbance in a Stenosed Carotid Artery Bifurcation Using Two-Equation Transitional and Turbulence Models
,”
ASME J. Biomech. Eng.
,
130
(
6
), p.
061008
.10.1115/1.2978992
45.
Kim
,
C. S.
,
Kiris
,
C.
,
Kwak
,
D.
, and
David
,
T.
,
2006
, “
Numerical Simulation of Local Blood Flow in the Carotid and Cerebral Arteries Under Altered Gravity
,”
ASME J. Biomech. Eng.
,
128
(
2
), pp.
194
202
.10.1115/1.2165691
You do not currently have access to this content.