Abstract

Atherosclerosis develops at arterial sites where endothelial cells (ECs) are exposed to low time-averaged shear stress, in particular in regions of recirculating disturbed flow. To understand how hemodynamics contributes to EC dysfunction in atheroma development, an in vitro parallel plate flow chamber gasket was modified with protruding baffles to produce large recirculating flow regions. Computational fluid dynamics (CFD) predicted that more than 60% of the flow surface area was below the 12 dynes/cm2 atheroprotective threshold. Bovine aortic endothelial cells (BAECs) were then seeded in the parallel plate flow chamber with either the standard laminar or the new disturbed flow gasket (DFG) and exposed to flow for 36 h. Cell morphology, nitric oxide (NO), proliferation, permeability, and monocyte adhesion were assessed by phase contrast and confocal microscopy. BAEC exposed to 20 dynes/cm2 shear stress in the laminar flow device aligned and elongated in the flow direction while increasing nitric oxide, decreasing permeability, and maintaining low proliferation and monocyte adhesion. BAEC in the recirculating flow and low shear stress disturbed flow device regions did not elongate or align, produced less nitric oxide, and showed higher proliferation, permeability, and monocyte adhesion than cells in the laminar flow device. However, cells in disturbed flow device regions exposed to atheroprotective shear stress did not consistently align or decrease permeability, and these cells demonstrated low nitric oxide levels. The new parallel plate DFG provides a means to study recirculating flow, highlighting the complex relationship between hemodynamics and endothelial function.

References

References
1.
Davies
,
P. F.
,
Civelek
,
M.
,
Fang
,
Y.
, and
Fleming
,
I.
,
2013
, “
The Atherosusceptible Endothelium: Endothelial Phenotypes in Complex Haemodynamic Shear Stress Regions In Vivo
,”
Cardiovasc. Res.
,
99
(
2
), pp.
315
327
.10.1093/cvr/cvt101
2.
Barbee
,
K. A.
,
Davies
,
P. F.
, and
Lal
,
R.
,
1994
, “
Shear Stress-Induced Reorganization of the Surface Topography of Living Endothelial Cells Imaged by Atomic Force Microscopy
,”
Circ. Res.
,
74
(
1
), pp.
163
171
.10.1161/01.RES.74.1.163
3.
Conway
,
D. E.
,
Coon
,
B. G.
,
Budatha
,
M.
,
Arsenovic
,
P. T.
,
Orsenigo
,
F.
,
Wessel
,
F.
,
Zhang
,
J.
,
Zhuang
,
Z.
,
Dejana
,
E.
,
Vestweber
,
D.
, and
Schwartz
,
M. A.
,
2017
, “
VE-Cadherin Phosphorylation Regulates Endothelial Fluid Shear Stress Responses Through the Polarity Protein LGN
,”
Curr. Biol.
, 27(14), pp.
2219
2225
.
4.
Coon
,
B. G.
,
Baeyens
,
N.
,
Han
,
J.
,
Budatha
,
M.
,
Ross
,
T. D.
,
Fang
,
J. S.
,
Yun
,
S.
,
Thomas
,
J. L.
, and
Schwartz
,
M. A.
,
2015
, “
Intramembrane Binding of VE-Cadherin to VEGFR2 and VEGFR3 Assembles the Endothelial Mechanosensory Complex
,”
J. Cell Biol.
,
208
(
7
), pp.
975
986
.10.1083/jcb.201408103
5.
Kim
,
D. W.
,
Gotlieb
,
A. I.
, and
Langille
,
B. L.
,
1989
, “
In Vivo Modulation of Endothelial F-Actin Microfilaments by Experimental Alterations in Shear Stress
,”
Aeteriosclerosis
,
9
(
4
), pp.
439
445
.10.1161/01.ATV.9.4.439
6.
Kemeny
,
S. F.
, and
Clyne
,
A. M.
,
2011
, “
A Simplified Implementation of Edge Detection in MATLAB Is Faster and More Sensitive Than Fast Fourier Transform for Actin Fiber Alignment Quantification
,”
Microsc. Microanal.
,
17
(
2
), pp.
156
166
.10.1017/S143192761100002X
7.
Wozniak
,
M. A.
,
Modzelewska
,
K.
,
Kwong
,
L.
, and
Keely
,
P. J.
,
2004
, “
Focal Adhesion Regulation of Cell Behavior
,”
Biochim. Biophys. Acta, Mol. Cell Res.
, 1692(2–3), pp.
103
119
.
8.
Galbraith
,
G. G.
,
Skalak
,
R.
, and
Chien
,
S.
,
1998
, “
Shear Stress Induces Spatial Reorganization of the Endothelial Cell Cytoskeleton
,”
Cell Motil. Cytoskeleton
,
40
(
4
), p.
317
.10.1002/(SICI)1097-0169(1998)40:4<317::AID-CM1>3.0.CO;2-8
9.
Miao
,
H.
,
Hu
,
Y.-L.
,
Shiu
,
Y.-T.
,
Yuan
,
S.
,
Zhao
,
Y.
,
Kaunas
,
R.
,
Wang
,
Y.
,
Jin
,
G.
,
Usami
,
S.
, and
Chien
,
S.
,
2005
, “
Effect of Flow Patterns on the Localization and Expression of VE-Cadherin at Vascular Endothelial Cell Junctions: In Vivo and In Vitro Investigations
,”
J. Vasc. Res.
,
42
(
1
), p.
77
.10.1159/000083094
10.
Gavard
,
J.
, and
Gutkind
,
J. S.
,
2006
, “
VEGF Controls Endothelial-Cell Permeability by Promoting the Beta-Arrestin-Dependent Endocytosis of VE-Cadherin
,”
Nat. Cell Biol.
,
8
(
11
), pp.
1223
1234
.10.1038/ncb1486
11.
Schulte
,
D.
,
Kuppers
,
V.
,
Dartsch
,
N.
,
Broermann
,
A.
,
Li
,
H.
,
Zarbock
,
A.
,
Kamenyeva
,
O.
,
Kiefer
,
F.
,
Khandoga
,
A.
,
Massberg
,
S.
, and
Vestweber
,
D.
,
2011
, “
Stabilizing the VE-Cadherin-Catenin Complex Blocks Leukocyte Extravasation and Vascular Permeability
,”
EMBO J.
,
30
(
20
), pp.
4157
4170
.10.1038/emboj.2011.304
12.
Cerutti
,
C.
, and
Ridley
,
A. J.
,
2017
, “
Endothelial Cell-Cell Adhesion and Signaling
,”
Exp. Cell Res.
, 358(1), pp.
31
38
.10.1016/j.yexcr.2017.06.003
13.
Chiu
,
J. J.
,
Chen
,
C. N.
,
Lee
,
P. L.
,
Yang
,
C. T.
,
Chuang
,
H. S.
,
Chien
,
S.
, and
Usami
,
S.
,
2003
, “
Analysis of the Effect of Disturbed Flow on Monocytic Adhesion to Endothelial Cells
,”
J. Biomech.
,
36
(
12
), pp.
1883
1895
.10.1016/S0021-9290(03)00210-0
14.
Tardy
,
Y.
,
Resnick
,
N.
,
Nagel
,
T.
,
Gimbrone
,
M. A.
, Jr.
, and
Dewey
,
C. F.
,
1997
, “
Shear Stress Gradients Remodel Endothelial Monolayers In Vitro Via a Cell-Proliferation-Migration-Loss Cycle
,”
Arterioscler. Thromb. Vasc. Biol.
,
17
(
11
), pp.
3102
3106
.10.1161/01.ATV.17.11.3102
15.
Won
,
D.
,
Zhu
,
S. N.
,
Chen
,
M.
,
Teichert
,
A. M.
,
Fish
,
J. E.
,
Matouk
,
C. C.
,
Bonert
,
M.
,
Ojha
,
M.
,
Marsden
,
P. A.
, and
Cybulsky
,
M. I.
,
2007
, “
Relative Reduction of Endothelial Nitric-Oxide Synthase Expression and Transcription in Atherosclerosis-Prone Regions of the Mouse Aorta and in an In Vitro Model of Disturbed Flow
,”
Am. J. Pathol.
,
171
(
5
), pp.
1691
1704
.10.2353/ajpath.2007.060860
16.
Heo
,
K.-S.
,
Fujiwara
,
K.
, and
Abe
,
J.
,
2011
, “
Disturbed-Flow-Mediated Vascular Reactive Oxygen Species Induce Endothelial Dysfunction
,”
Circ. J.
,
75
(
12
), pp.
2722
2730
.10.1253/circj.CJ-11-1124
17.
Chiu
,
J. J.
, and
Chien
,
S.
,
2011
, “
Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives
,”
Physiol. Rev.
,
91
(
1
), pp.
327
387
.10.1152/physrev.00047.2009
18.
Jenkins
,
N. T.
,
Padilla
,
J.
,
Boyle
,
L. J.
,
Credeur
,
D. P.
,
Laughlin
,
M. H.
, and
Fadel
,
P. J.
,
2013
, “
Disturbed Blood Flow Acutely Induces Activation and Apoptosis of the Human Vascular Endothelium
,”
Hypertension
,
61
(
3
), pp.
615
621
.10.1161/HYPERTENSIONAHA.111.00561
19.
Sorescu
,
G. P.
,
Sykes
,
M.
,
Weiss
,
D.
,
Platt
,
M. O.
,
Saha
,
A.
,
Hwang
,
J.
,
Boyd
,
N.
,
Boo
,
Y. C.
,
Vega
,
J. D.
,
Taylor
,
W. R.
, and
Jo
,
H.
,
2003
, “
Bone Morphogenic Protein 4 Produced in Endothelial Cells by Oscillatory Shear Stress Stimulates an Inflammatory Response
,”
J. Biol. Chem.
,
278
(
33
), pp.
31128
31135
.10.1074/jbc.M300703200
20.
Dolan
,
J. M.
,
Meng
,
H.
,
Sim
,
F. J.
, and
Kolega
,
J.
,
2013
, “
Differential Gene Expression by Endothelial Cells Under Positive and Negative Streamwise Gradients of High Wall Shear Stress
,”
Am. J. Physiol. Cell Physiol.
, 305(8), pp. C854–C866.10.1152/ajpcell.00315.2012
21.
Szymanski
,
M. P.
,
Metaxa
,
E.
,
Meng
,
H.
, and
Kolega
,
J.
,
2008
, “
Endothelial Cell Layer Subjected to Impinging Flow Mimicking the Apex of an Arterial Bifurcation
,”
Ann. Biomed. Eng.
,
36
(
10
), pp.
1681
1689
.10.1007/s10439-008-9540-x
22.
Noris
,
M.
,
Morigi
,
M.
,
Donadelli
,
R.
,
Aiello
,
S.
,
Foppolo
,
M.
,
Todeschini
,
M.
,
Orisio
,
S.
,
Remuzzi
,
G.
,
Remuzzi
,
A.
,
Noris
,
M.
,
Todeschini
,
M.
,
Orisio
,
S.
,
Remuzzi
,
G.
, and
Remuzzi
,
A.
,
1995
, “
Nitric Oxide Synthesis by Cultured Endothelial Cells Is Modulated by Flow Conditions
,”
Circ. Res.
,
76
(
4
), pp.
536
543
.10.1161/01.RES.76.4.536
23.
Dewey
,
C. F.
,
Bussolari
,
S. R.
,
Gimbrone
,
M. A.
, and
Davies
,
P. F.
,
1981
, “
The Dynamic Response of Vascular Endothelial Cells to Fluid Shear Stress
,”
ASME J. Biomech. Eng.
,
103
(
3
), p.
177
.10.1115/1.3138276
24.
Buschmann
,
M. H.
,
Dieterich
,
P.
,
Adams
,
N. A.
, and
Schnittler
,
H. J.
,
2005
, “
Analysis of Flow in a Cone-and-Plate Apparatus With Respect to Spatial and Temporal Effects on Endothelial Cells
,”
Biotechnol. Bioeng.
,
89
(
5
), pp.
493
502
.10.1002/bit.20165
25.
Franzoni
,
M.
,
Cattaneo
,
I.
,
Ene-Iordache
,
B.
,
Oldani
,
A.
,
Righettini
,
P.
, and
Remuzzi
,
A.
,
2016
, “
Design of a Cone-and-Plate Device for Controlled Realistic Shear Stress Stimulation on Endothelial Cell Monolayers
,”
Cytotechnology
,
68
(
5
), pp.
1885
1896
.10.1007/s10616-015-9941-2
26.
Brown
,
T. D.
,
2000
, “
Techniques for Mechanical Stimulation of Cells In Vitro: A Review
,”
J. Biomech.
,
33
(
1
), pp.
3
14
.10.1016/S0021-9290(99)00177-3
27.
Dardik
,
A.
,
Chen
,
L.
,
Frattini
,
J.
,
Asada
,
H.
,
Aziz
,
F.
,
Kudo
,
F. A.
, and
Sumpio
,
B. E.
,
2005
, “
Differential Effects of Orbital and Laminar Shear Stress on Endothelial Cells
,”
J. Vasc. Surg.
,
41
(
5
), pp.
869
880
.10.1016/j.jvs.2005.01.020
28.
Lu
,
Y.
,
Li
,
W.
,
Oraifige
,
I.
, and
Wang
,
W.
,
2014
, “
Converging Parallel Plate Flow Chambers for Studies on the Effect of the Spatial Gradient of Wall Shear Stress on Endothelial Cells
,”
J. Biosci. Med.
,
2
, pp.
50
56
.10.4236/jbm.2014.22008
29.
DePaola
,
N.
,
Davies
,
P. F.
,
Pritchard
,
W. F.
,
Florez
,
L.
,
Harbeck
,
N.
, and
Polacek
,
D. C.
,
1999
, “
Spatial and Temporal Regulation of Gap Junction Connexin43 in Vascular Endothelial Cells Exposed to Controlled Disturbed Flows In Vitro
,”
Proc. Natl. Acad. Sci.
, 96(6), pp.
3154
3159
.10.1073/pnas.96.6.3154
30.
Kock
,
S. A.
,
Nygaard
,
J. V.
,
Eldrup
,
N.
,
Fründ
,
E. T.
,
Klærke
,
A.
,
Paaske
,
W. P.
,
Falk
,
E.
, and
Yong Kim
,
W.
,
2008
, “
Mechanical Stresses in Carotid Plaques Using MRI-Based Fluid-Structure Interaction Models
,”
J. Biomech.
, 41(8), pp.
1651
1658
.10.1016/j.jbiomech.2008.03.019
31.
Slagger
,
C. J.
,
Wentzell
,
J. J.
,
Gijsen
,
F. J. H.
,
Thury
,
A.
,
van der Waal
,
A. C.
,
Schaar
,
J. A.
, and
Serruys
,
P. W.
,
2005
, “
The Role of Shear Stress in the Destabilization of Vulnerable Plaques and Related Therapeutic Implications
,”
Nat. Clin. Pract. Cardiovasc. Med.
, 2(9), pp.
456
464
.10.1038/ncpcardio0298
32.
Itoh
,
Y.
,
Ma
,
F. H.
,
Hoshi
,
H.
,
Oka
,
M.
,
Noda
,
K.
,
Ukai
,
Y.
,
Kojima
,
H.
,
Nagano
,
T.
, and
Toda
,
N.
,
2000
, “
Determination and Bioimaging Method for Nitric Oxide in Biological Specimens by Diaminofluorescein Fluorometry
,”
Anal. Biochem.
,
287
(
2
), pp.
203
209
.10.1006/abio.2000.4859
33.
Dubrovskyi
,
O.
,
Birukova
,
A. A.
, and
Birukov
,
K.
,
2013
, “
Measurement of Local Permeability at Subcellular Level in Cell Models of Agonist- and Ventilator-Induced Lung Injury
,”
Lab. Invest.
,
93
(
2
), pp.
254
263
.10.1038/labinvest.2012.159
34.
Maltsev
,
V. P.
,
Hoekstra
,
A. G.
, and
Yurkin
,
M. A.
,
2011
, “
Optics of White Blood Cells: Optical Models, Simulations, and Experiments
,”
Advanced Optical Flow Cytometry: Methods and Disease Diagnoses
, Wiley, Hoboken, NJ, Chap.
4
.
35.
Schoch
,
R. L.
,
Kapinos
,
L. E.
, and
Lim
,
R. Y. H.
,
2012
, “
Supporting Information: Nuclear Transport Receptor Binding Avidity Triggers a Self-Healing Collapse Transition in FG-Nucleoporin Molecular Brushes
,”
PNAS
,
109
(
42
), pp.
16911
16916
.10.1073/pnas.1208440109
36.
Canver
,
A. C.
, and
Clyne
,
A. M.
,
2017
, “
Quantification of Multicellular Organization, Junction Integrity, and Substrate Features in Collective Cell Migration
,”
Microsc. Microanal.
,
23
(
1
), pp.
22
33
.10.1017/S1431927617000071
37.
Scholzen
,
T.
, and
Gerdes
,
J.
,
2000
, “
The Ki-67 Protein: From the Known and the Unknown
,”
J. Cell. Physiol.
, 182(3), pp.
311
322
.10.1002/(SICI)1097-4652(200003)182:33.0.CO;2-9
38.
Otsu
,
N.
,
1979
, “
A Threshold Selection Method From Gray-Level Histograms
,”
IEEE Trans. Syst. Man. Cybern.
, 9(1), pp.
62
66
.10.1109/TSMC.1979.4310076
39.
Kornilov
,
A.
, and
Safonov
,
I.
,
2018
, “
An Overview of Watershed Algorithm Implementations in Open Source Libraries
,”
J. Imaging
,
4
(
10
), p.
123
.10.3390/jimaging4100123
40.
Kohn
,
J. C.
,
Zhou
,
D. W.
,
Bordeleau
,
F.
,
Zhou
,
A. L.
,
Mason
,
B. N.
,
Mitchell
,
M. J.
,
King
,
M. R.
, and
Reinhart-King
,
C. A.
,
2015
, “
Cooperative Effects of Matrix Stiffness and Fluid Shear Stress on Endothelial Cell Behavior
,”
Biophys. J.
,
108
(
3
), pp.
471
478
.10.1016/j.bpj.2014.12.023
41.
Heo
,
K. S.
,
Lee
,
H.
,
Nigro
,
P.
,
Thomas
,
T.
,
Le
,
N. T.
,
Chang
,
E.
,
McClain
,
C.
,
Reinhart-King
,
C. A.
,
King
,
M. R.
,
Berk
,
B. C.
,
Fujiwara
,
K.
,
Woo
,
C. H.
, and
Abe
,
J.
,
2011
, “
PKCzeta Mediates Disturbed Flow-Induced Endothelial Apoptosis Via P53 SUMOylation
,”
J. Cell Biol.
,
193
(
5
), pp.
867
884
.10.1083/jcb.201010051
42.
Davies
,
P. F.
,
Remuzzi
,
A.
,
Gordon
,
E. J.
,
Dewey
,
C. F.
, and
Gimbrone
,
M. A.
,
1986
, “
Turbulent Fluid Shear Stress Induces Vascular Endothelial Cell Turnover In Vitro
,”
Proc. Natl. Acad. Sci. U. S. A.
,
83
(
7
), pp.
2114
2117
.10.1073/pnas.83.7.2114
43.
DePaola
,
N.
,
Gimbrone
,
M. A.
,
Davies
,
P. F.
, and
Dewey
,
C. F.
,
1992
, “
Vascular Endothelium Responds to Fluid Shear Stress Gradients
,”
Arterioscler. Thromb. Vasc. Biol.
,
12
(
11
), pp.
1254
1257
.10.1161/01.ATV.12.11.1254
44.
Estrada
,
R.
,
Giridharan
,
G. A.
,
Nguyen
,
M. D.
,
Prabhu
,
S. D.
, and
Sethu
,
P.
,
2011
, “
Microfluidic Endothelial Cell Culture Model to Replicate Disturbed Flow Conditions Seen in Atherosclerosis Susceptible Regions
,”
Biomicrofluidics
,
5
(
3
), p.
032006
.10.1063/1.3608137
45.
Patibandla
,
P. K.
,
Rogers
,
A. J.
,
Giridharan
,
G. A.
,
Pallero
,
M. A.
,
Murphy-Ullrich
,
J. E.
, and
Sethu
,
P.
,
2014
, “
Hyperglycemic Arterial Disturbed Flow Niche as an In Vitro Model of Atherosclerosis
,”
Anal. Chem.
,
86
(
21
), pp.
10948
10954
.10.1021/ac503294p
46.
Wang
,
X. Q.
,
Nigro
,
P.
,
World
,
C.
,
Fujiwara
,
K.
,
Yan
,
C.
, and
Berk
,
B. C.
,
2012
, “
Thioredoxin Interacting Protein Promotes Endothelial Cell Inflammation in Response to Disturbed Flow by Increasing Leukocyte Adhesion and Repressing Kruppel-Like Factor 2
,”
Circ. Res.
,
110
(
4
), pp.
560
568
.10.1161/CIRCRESAHA.111.256362
47.
Ostrowski
,
M. A.
,
Huang
,
N. F.
,
Walker
,
T. W.
,
Verwijlen
,
T.
,
Poplawski
,
C.
,
Khoo
,
A. S.
,
Cooke
,
J. P.
,
Fuller
,
G. G.
, and
Dunn
,
A. R.
,
2014
, “
Microvascular Endothelial Cells Migrate Upstream and Align Against the Shear Stress Field Created by Impinging Flow
,”
Biophys. J.
,
106
(
2
), pp.
366
374
.10.1016/j.bpj.2013.11.4502
48.
Launay
,
G.
,
Mignot
,
E.
,
Riviere
,
N.
, and
Perkins
,
R.
,
2017
, “
An Experimental Investigation of the Laminar Horseshoe Vortex Around an Emerging Obstacle
,”
J. Fluid Mech.
,
830
, p.
257
.10.1017/jfm.2017.582
49.
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
50.
Balcerczyk
,
A.
,
Soszynski
,
M.
, and
Bartosz
,
G.
,
2005
, “
On the Specificity of 4-Ammino-5-Methylamino-2′,7′-Diflurorofluorescein as a Probe for Nitric Oxide
,”
Free Radical Biol. Med.
,
39
(
3
), pp.
327
335
.10.1016/j.freeradbiomed.2005.03.017
51.
Valiunas
,
V.
,
Polosina
,
Y. Y.
,
Miller
,
H.
,
Potapova
,
I. A.
,
Valiuniene
,
L.
,
Doronin
,
S.
,
Mathias
,
R. T.
,
Robinson
,
R. B.
,
Rosen
,
M. R.
,
Cohen
,
I. S.
, and
Brink
,
P. R.
,
2005
, “
Connexin-Specific Cell-to-Cell Transfer of Short Interfering RNA by Gap Junctions
,”
J. Physiol.
, 568(2), pp.
459
468
.10.1113/jphysiol.2005.090985
52.
Thuringer
,
D.
,
Jego
,
G.
,
Berthenet
,
K.
,
Hammann
,
A.
,
Solary
,
E.
, and
Garrido
,
C.
,
2016
, “
Gap Junction-Mediated Transfer of MiR-145-5p From Microvascular Endothelial Cells to Colon Cancer Cells Inhibits Angiogenesis
,”
Oncotarget
,
7
(
19
), pp.
28160
28168
.10.18632/oncotarget.8583
53.
Zong
,
L.
,
Zhu
,
Y.
,
Liang
,
R.
, and
Zhao
,
H. B.
,
2016
, “
Gap Junction Mediated MiRNA Intercellular Transfer and Gene Regulation: A Novel Mechanism for Intercellular Genetic Communication
,”
Sci. Rep.
, 6, p.
19884
.10.1038/srep19884
54.
LaMack
,
J. A.
, and
Friedman
,
M. H.
,
2007
, “
Individual and Combined Effects of Shear Stress Magnitude and Spatial Gradient on Endothelial Cell Gene Expression
,”
Am. J. Physiol.: Heart Circ. Physiol.
, 293(5), pp. H2853–H2859.10.1152/ajpheart.00244.2007
55.
Balaguru
,
U. M.
,
Sundaresan
,
L.
,
Manivannan
,
J.
,
Majunathan
,
R.
,
Mani
,
K.
,
Swaminathan
,
A.
,
Venkatesan
,
S.
,
Kasiviswanathan
,
D.
, and
Chatterjee
,
S.
,
2016
, “
Disturbed Flow Mediated Modulation of Shear Forces on Endothelial Plane: A Proposed Model for Studying Endothelium Around Atherosclerotic Plaques
,”
Sci. Rep.
,
6
(
1
), p.
27304
.10.1038/srep27304
56.
Deshmane
,
S. L.
,
Kremlev
,
S.
,
Amini
,
S.
, and
Sawaya
,
B. E.
,
2009
, “
Monocyte Chemoattractant Protein-1 (MCP-1): An Overview
,”
J. Interferon Cytokine Res.
, 29(6), pp.
313
326
.10.1089/jir.2008.0027
57.
Shyy
,
J. Y. J.
, and
Chien
,
S.
,
2002
, “
Role of Integrins in Endothelial Mechanosensing of Shear Stress
,”
Circ. Res.
, 91(9), pp.
769
775
.10.1161/01.RES.0000038487.19924.18
58.
Huang
,
D. L.
,
Bax
,
N. A.
,
Buckley
,
C. D.
,
Weis
,
W. I.
, and
Dunn
,
A. R.
,
2017
, “
Vinculin Forms a Directionally Asymmetric Catch Bond With F-Actin
,”
Science
,
357
(
6352
), p.
703
.10.1126/science.aan2556
59.
Yoshino
,
D.
,
Sakamoto
,
N.
, and
Sato
,
M.
,
2017
, “
Fluid Shear Stress Combined With Shear Stress Spatial Gradients Regulates Vascular Endothelial Morphology
,”
Integr. Biol.
,
9
(
7
), p.
584
.10.1039/C7IB00065K
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