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1.
Venetsanou K Fildissis G Tokta R Brinias C Baltopoulos G 《European journal of applied physiology》2012,112(2):677-687
Nitric oxide (NO) acts as a regulator in cell proliferation and expression of growth factors and forms peroxynitrite (ONOO−) in oxidative conditions. The aim of the study was to investigate the role of NO in cellular response to hyperbaric oxygen
(HBO). NO and nitrotyrosine (NT), biochemical marker for ONOO−, cell proliferation and growth factors, were ex-vivo studied in cell cultures under HBO and normobaric (NOR) conditions.
A549 (epithelial), L929 (fibroblast) and SVEC (endothelial) were exposed to 100% O2, at P = 280 kPa for t = 60 min, once daily for five sessions. Cell proliferation was determined as the incorporation of bromodeoxyuridine (BrdU)
into cells and NO as nitrates/nitrites (NO3
−/ NO2
−) Gries reaction product in cell culture supernatant (CCSP). NT, vascular endothelial growth factor (VEGF) and transforming
growth factor-beta 1 (TGFb1) were measured with enzyme-inked immunosorbent assay (ELISA) in CCSP. The time course of total
NO was opposite to that of cell proliferation in HBO conditions, peaking after the second HBO session, while cell proliferation
showed a reverse trend, minimizing at the same time, suggesting a reverse and transient anti-proliferative effect. Released
growth factors were significantly increased in late HBO sessions. NT peaked after second treatment, indicating the formation
of ONOO−. In control cultures (NOR), proliferation rate was downward and no significant differences were found for the other parameters.
In conclusion, the data suggested a key role for NO in the beneficial HBO action, depending on its concentration, which fluctuated
with the time of HBO exposure and the activation of oxidant–antioxidant (REDOX) mechanisms, regardless of cell type. 相似文献
2.
We have utilized soft lithography techniques to create three-dimensional arrays of blood microchannels and gas pathways in
poly(dimethylsiloxane) (PDMS) that approach the microvascular scale of the natural lung. The blood microchannels were lined
with endothelial cells in an effort to provide a non-thrombogenic surface that might ultimately reduce the need for systemic
anticoagulation. A novel design and fabrication method were developed to create prototype modules for gas permeance and cell
culture testing. The gas permeance modules contained 6 layers, four gas and two blood, while the modules for cell culture
testing contained two layers of blood channels. The gas permeance of the modules was examined and maximum values of 9.16 × 10−6 and 3.55 × 10−5 mL/s/cm2/cmHg, for O2 and CO2 respectively, were obtained. Finally, endothelial cells were seeded and dynamically cultured in prototype cell culture modules.
Confluent and viable cell monolayers were achieved after 10 days of perfusion. 相似文献
3.
4.
Xin Huang Stefan Zauscher Bruce Klitzman George A. Truskey William M. Reichert Daniel J. Kenan Mark W. Grinstaff 《Annals of biomedical engineering》2010,38(6):1965-1976
Resorbable scaffolds such as polyglycolic acid (PGA) are employed in a number of clinical and tissue engineering applications
owing to their desirable property of allowing remodeling to form native tissue over time. However, native PGA does not promote
endothelial cell adhesion. Here we describe a novel treatment with hetero-bifunctional peptide linkers, termed “interfacial
biomaterials” (IFBMs), which are used to alter the surface of PGA to provide appropriate biological cues. IFBMs couple an
affinity peptide for the material with a biologically active peptide that promotes desired cellular responses. One such PGA
affinity peptide was coupled to the integrin binding domain, Arg-Gly-Asp (RGD), to build a chemically synthesized bimodular
27 amino acid peptide that mediated interactions between PGA and integrin receptors on endothelial cells. Quartz crystal microbalance
with dissipation monitoring (QCMD) was used to determine the association constant (K
A 1 × 107 M−1) and surface thickness (~3.5 nm). Cell binding studies indicated that IFBM efficiently mediated adhesion, spreading, and
cytoskeletal organization of endothelial cells on PGA in an integrin-dependent manner. We show that the IFBM peptide promotes
a 200% increase in endothelial cell binding to PGA as well as 70–120% increase in cell spreading from 30 to 60 minutes after
plating. 相似文献
5.
Mutsumi Takagi PhD Toshihide Haraguchi PhD Hisanori Kawai BS Kouji Shiwaku BS Takeomi Inoue MS Yoshiki Sawa MD PhD Hikaru Matsuda MD PhD Toshiomi Yoshida PhD 《Journal of artificial organs》2001,4(3):220-225
The effect of plasma discharge treatment of a microporous polypropylene hollow-fiber membrane commonly used for gas exchange
in a conventional artificial lung on the adhesion of endothelial cells was investigated with the aim of constructing a hybrid
artificial lung bearing endothelial cells on the membrane. The initial adhesion density and growth rate of the cells on the
membrane were markedly increased following plasma discharge treatment (13.56 MHz, 30W) of the membrane for 5 to 20 min in
the presence of 0.05 mmHg of various gases, such as ammonia, oxygen, and water vapor. Treatment of the membrane with ammonia
for 5 min resulted in the highest increase in the cell adhesion density on 5 days from 1.4×102 to 2.0×103 cells/cm2, and the cell density reached 5.0×103 cells/cm2 after cultivation for 14 days. Increasing the inoculum cell concentration from 3.3×105 to 3.2×106 cells/ml resulted in an initial cell adhesion of 0.9×105 cells/cm2, even after 1 day. It was observed under a microscope that the cells were distributed uniformly to cover almost all of the
surface area of the membrane. After the plasma discharge treatment, the permeability of the membrane to water increased to
9% of that of a polyethylene hollow fiber having pore diameters larger than 0.4 μm. 相似文献
6.
Neutrophils isolated from human peripheral blood added to a monolayer of human endothelial cells (ECV-304 cell line) stimulated
with LPS (100 ng ml−1) resulted in: (a) neutrophil activation, measured by spreading and release of leukotriene B4 (LTB4); (b) neutrophil degranulation, measured by release of matrix pro-metalloproteinase-9 (proMMP-9) and (c) loss of the monolayer
integrity due to detachment of the endothelial cells. Stimulation of endothelial cells with tumor necrosis factor-α (TNF-α
10 ng ml−1) or interleukin-1 (IL-1; 10 ng ml−1) induced a similar dose-dependent increase in the neutrophil activation and endothelial cell detachment. Pre-treatment of
LPS-activated ECV-304 cells with [Phe22]BigET-1(19–37) (10−9 M; an inhibitor of endothelin converting enzyme (ECE)) or addition of BQ-123 (10−6 M; a selective endothelin A (ETA) receptor antagonist) to the co-cultures, significantly reduced neutrophil spreading (50–70% inhibition) as well as the levels
of LTB4 (70–100% inhibition) and proMMP-9 (40–50% inhibition) in the co-culture supernatants. In addition, the detachment of endothelial
cells was also reduced (60–75% inhibition). Moreover, the exogenous addition of ET-1 (10−9 M) to neutrophil suspensions induced neutrophil spreading and release of LTB4 and proMMP-9. Taken together, these findings indicate that neutrophils added to stimulated endothelial cells in the co-culture
system employed in this study, get activated by products of these cells and degranulate. In parallel, the detachment of endothelial
cell monolayer from the culture plates, possibly by the action of neutrophil granule-derived gelatinases, is observed. Endothelins
(ETs) produced by the endothelial cells are suggested to play an essential role in these phenomena. 相似文献
7.
Polarographic current transients following a voltage step (turn-on transient) were measured with bare cathodes (25 μm diameter)
and shallowly recessed oxygen microelectrodes (<5μm diameter). Except for the initial part of the current transient, the experimental
measurements were in excellent agreement with simple models in the literature, which predict an inverse relationship with
. Turn-on transients were measured in aqueous solutions with known physical properties, and in aortic wall tissue from three
different species (n=6 rabbits, n=3 dogs, and n=1 miniature pig). Oxygen diffusion coefficients (D) were determinedin vitro by comparing time constants measured by the same microelectrode in saline and in strips of aortic wall tissue at 37°C. On
the inner side (endothelium and intima) of the aorta, D averaged (±S.E.) 7.0 (±0.8)×10−6 cm2/s in 6 rabbits, 6.4 (±1.0)×10−6 cm2/s in 3 dogs, and was 4.6×10−6 cm2/s in the pig. On the adventitial side, D was 9.5×10−6 cm2/s in 1 rabbit, 11.4 (±1.2)×10−6 cm2/s in 3 dogs, and 8.1×10−6 cm2/s in the pig. For every aortic strip on which D was measured from both sides, D for the inner wall was always lower, overall
by a little more than one third (p<0.001). The lower D on the endothelial side may limit oxygen transport to the vascular
wall and play a role in atherogenesis. 相似文献
8.
Patricia A. Gonnella Pedro J. Del Nido Francis X. McGowan 《Journal of clinical immunology》2009,29(4):434-443
Introduction Experimental autoimmune myocarditis (EAM) is mediated by myocardial infiltration by myosin-specific T cells secreting inflammatory
cytokines.
Materials and methods To clarify the role of cytokines in EAM, we compared STAT 6-deficient (−/−) with STAT 4−/− and wild-type (BALB/CJ) mice following immunization with cardiac myosin peptide (614–629).
Results Wild-type mice developed severe disease with a small increase in severity in STAT 6−/− mice, while STAT 4−/− mice were resistant to EAM. STAT 6−/− mice had increased splenocyte proliferation and INF-γ production versus wild type, while STAT 4−/− mice had decreased proliferation and INF-γ. Following oral administration of myosin (614–629), tolerization was induced in
wild-type mice evidenced by amelioration of myocarditis and up-regulation of IL-4. Adoptive transfer of splenocytes from orally
tolerized mice resulted in inhibition of disease in STAT 6−/− mice.
Conclusion These results demonstrate that oral tolerization ameliorates EAM in BALB/CJ mice and indicate a down-regulatory role for STAT
6 genes. 相似文献
9.
Endothelial cells in vivo are exposed to blood shear forces and flow perturbations induce their activation. Such modifications of hemodynamic can be
observed in patients with cancer. We have submitted endothelial cells (HUVEC) to shear stress (13 dynes/cm2) and isolated their extracellular matrix (ECM) prior perfusion with breast adenocarcinoma cells (MDA-MB-231) in whole blood
at a shear rate of 1500 s−1. Exposure of HUVEC to 13 dynes/cm2 (τ13) for 2 h enhanced the secretion of von Willebrand factor (vWF) and thrombospondin-1 (TSP-1) in the ECM. Moreover, MDA-MB-231
cell adhesion was enhanced to such treated-ECM. This over-adhesion was inhibited by pre-incubating the ECM with anti-vWF or
anti-TSP-1 antibodies, or by blocking tumour cell αvβ3 integrin. Although blood platelets were involved in tumour cell adhesion to ECM, blockade of platelet GPIb or αIIbβ3 receptors did not specifically inhibit the enhanced tumour cell adhesion observed on τ13. ECM. These findings indicate that shear stress can modulate the expression of adhesive proteins in ECM, which favours direct
tumour cell adhesion via αvβ3 and other receptors. 相似文献
10.
Jones CI Zhu H Martin SF Han Z Li Y Alevriadou BR 《Annals of biomedical engineering》2007,35(5):683-693
Exposure of vascular endothelial cells (ECs) to steady laminar shear stress activates the NF-E2-related factor 2 (Nrf2) which
binds to the antioxidant response element (ARE) and upregulates the expression of several genes. The onset of shear is known
to increase the EC reactive oxygen species (ROS) production, and oxidative stress can activate the ARE. ARE-regulated genes
include phase 2 enzymes, such as glutathione-S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), and antioxidants, such as glutathione reductase (GR), glutathione
peroxidase (GPx) and catalase. We examined how shear stress affects the antioxidant/phase 2 enzyme activities and whether
ROS mediate these effects. ROS production, measured by dichlorofluorescin fluorescence, depended on level and time of shear
exposure and EC origin, and was inhibited by either an endothelial nitric oxide synthase (eNOS) inhibitor or a superoxide
dismutase (SOD) mimetic and peroxynitrite (ONOO−) scavenger. Shear stress (10 dynes/cm2, 16 h) significantly increased the NQO1 activity, did not change significantly the glutathione (GSH) content, and significantly
decreased the GR, GPx, GST and catalase activities in human umbilical vein ECs. Either eNOS inhibition or superoxide radical
(O2•−)/ONOO− scavenging differentially modulated the shear effects on enzyme activities suggesting that the intracellular redox status
coordinates the shear-induced expression of cytoprotective genes. 相似文献
11.
Endothelial Cell Layer Subjected to Impinging Flow Mimicking the Apex of an Arterial Bifurcation 总被引:1,自引:0,他引:1
Little is known about endothelial responses to the impinging flow hemodynamics that occur at arterial bifurcation apices,
where intracranial aneurysms usually form. Such hemodynamic environments are characterized by high wall shear stress (WSS
>40 dynes/cm2) and high wall shear stress gradients (WSSG >300 dynes/cm3). In this study, confluent bovine aortic endothelial cells were exposed to impinging flow in a T-shaped chamber designed
to mimic a bifurcation. After 24–72 h under flow, cells around the stagnation point maintained polygonal shapes but cell density
was reduced, whereas cells in adjacent downstream regions exposed to very high WSS and WSSG were elongated, aligned parallel
to flow, and at higher density. Such behavior was not blocked by inhibiting proliferation, indicating that cells migrated
downstream from the stagnation point in response to impinging flow. Furthermore, although the area of highest cell density
moved downstream and away from the impingement point over time, it never moved beyond the WSS maximum. The accumulation of
cells upstream of maximal WSS and downstream of maximal WSSG suggests that positive WSSG is responsible for the observed migration.
These results demonstrate a unique endothelial response to aneurysm-promoting flow environments at bifurcation apices. 相似文献
12.
Lior Dayan Andrew P. Levy Shany Blum Rachel Miller-Lotan Uzi Melman Jonia Alshiek Giris Jacob 《European journal of applied physiology》2009,106(4):639-644
Endothelial function (EnF) is impaired in patients with diabetes mellitus (DM) due in large part to an increase in oxidative
stress. Haptoglobin (Hp) is a potent antioxidant protein which is encoded by two different alleles (1 and 2) with the Hp 1
protein being a superior antioxidant to the Hp 2 protein. We hypothesized that DM individuals with the Hp 2-2 genotype would
have greater endothelial dysfunction as compared to DM individuals with the Hp 1-1 genotype. We studied EnF in 16 Hp 2-2,
14 Hp 1-1 DM individuals and 14 healthy subjects. DM patients’ groups were matched in terms of age, cardiovascular risk factors
and metabolic characteristics. EnF was assessed using post-ischemic reactive hyperemia and strain gauge plethysmography and
expressed either as the maximal flow after the ischemic period or as the area under the flow–time curve (AUC). We showed that
EnF indices, AUC and maximal flow, were also higher in the healthy and Hp 1-1 groups compared with Hp 2-2 genotype group (615 ± 60
and 600 ± 40 vs. 450 ± 50 ml dl−1, 29 ± 2.6 and 25 ± 3 vs. 14 ± 1.8 ml min−1 dl−1, P < 0.003 and P < 0.05, for AUC and maximal flow, one-way ANOVA, respectively). We concluded that Hp 2-2 diabetic patients had a worse EnF
than controls and Hp 1-1 diabetic subjects. 相似文献
13.
Masaru Kojima Masami Suzuki Kazuhiko Shimizu Nobuhide Masawa 《Endocrine pathology》2009,20(3):186-190
Inflammatory pseudotumor of the thyroid gland (IPT) appears to be exceedingly rare. Histologically, 14 previously reported
cases demonstrated plasma cell granuloma variant. We report here an IPT showing a predominantly fibrohistiocytic proliferation
that occurred in a 75-year-old Japanese woman. Histologically, the lesion was characterized by haphazardly arranged spindle
cells, histiocytes having foamy cytoplasm containing intracytoplasmic brown pigments, and small lymphocytes. Immunohistochemical
study demonstrated that the spindle cells were vimentin+, desmin−, muscle-specific actin+, cytokeratin−, endomysial antibody−,
anaplastic lymphoma kinase−, CD34-− CD68+/−, CD99−, cyclin D1−, bcl-2−, and antifollicular dendritic cell antibody−. IPT showing
a predominant fibrohistiocytic proliferation should be differentiated from various nonneoplastic or neoplastic disorders showing
spindle cell proliferation and/or exuberant fibrosis. They include Riedel’s thyroiditis, fibrous variant of chronic thyroiditis,
papillary carcinoma with exuberant nodular fasciitis-like stroma, paucicellular variant of anaplastic thyroid carcinoma, and
solitary fibrous tumor. 相似文献
14.
Teichmann J Morgenstern A Seebach J Schnittler HJ Werner C Pompe T 《Biomaterials》2012,33(7):1959-1969
Endothelial cells constitute the natural inner lining of blood vessels and possess anti-thrombogenic properties. This characteristic is frequently used by seeding endothelial cells on vascular prostheses. As the type of anchorage of adhesion ligands to materials surfaces is known to determine the mechanical balance of adherent cells, we investigated herein the behaviour of endothelial cells under physiological shear stress conditions. The adhesion ligand fibronectin was anchored to polymer surfaces of four physicochemical characteristics exhibiting covalent and non-covalent attachment as well as high and low hydrophobicity. The in situ analysis combined with cell tracking of shear stress-induced effects on cultured isolated cells and monolayers under venous (0.5 dyn/cm2) and arterial (12 dyn/cm2) shear stress over a time period of 24 h revealed distinct differences in their morphological and migratory features. Most pronounced, unidirectional and bimodal migration patterns of endothelial cells in or against flow direction were found in dependence on the type of substrate-matrix anchorage. Combined by an immunofluorescent analysis of the actin cytoskeleton, cell-cell junctions, cell-matrix adhesions, and matrix reorganization these results revealed a distinct balance of laminar shear stress, cell-cell contacts and substrate-matrix anchorage in affecting endothelial cell fate under flow conditions. This analysis underlines the importance of materials surface parameters as well as primary and secondary adhesion ligand anchorage in the context of artificial blood vessels for future therapeutic devices. 相似文献
15.
《Biomaterials》2015
Clinical acceptance of photodynamic therapy is currently hindered by poor depth efficacy and inefficient activation of the cell death machinery in cancer cells during treatment. To address these issues, photoactivation using two-photon absorption (TPA) is currently being examined. Mitochondria-targeted therapy represents a promising approach to target tumors selectively and may overcome the resistance in current anticancer therapies. Herein, four ruthenium(II) polypyridyl complexes (RuL1–RuL4) have been designed and developed to act as mitochondria-targeted two-photon photodynamic anticancer agents. These complexes exhibit very high singlet oxygen quantum yields in methanol (0.74–0.81), significant TPA cross sections (124–198 GM), remarkable mitochondrial accumulation, and deep penetration depth. Thus, RuL1–RuL4 were utilized as one-photon and two-photon absorbing photosensitizers in both monolayer cells and 3D multicellular spheroids (MCSs). These Ru(II) complexes were almost nontoxic towards cells and 3D MCSs in the dark and generate sufficient singlet oxygen under one- and two-photon irradiation to trigger cell death. Remarkably, RuL4 exhibited an IC50 value as low as 9.6 μM in one-photon PDT (λirr = 450 nm, 12 J cm−2) and 1.9 μM in two-photon PDT (λirr = 830 nm, 800 J cm−2) of 3D MCSs; moreover, RuL4 is an order of magnitude more toxic than cisplatin in the latter test system. The combination of mitochondria-targeting and two-photon activation provides a valuable paradigm to develop ruthenium(II) complexes for PDT applications. 相似文献
16.
Rodger FE; Young FM; Fraser HM; Illingworth PJ 《Human reproduction (Oxford, England)》1997,12(8):1723-1729
The corpus luteum is essential for the maintenance of early pregnancy in
women. Angiogenesis may be one factor involved in luteal rescue. The aim of
this study was to determine the changes in endothelial cell proliferation
throughout the luteal phase and in human chorionic gonadotrophin
(HCG)-simulated early pregnancy. Human corpora lutea obtained throughout
the luteal phase and in simulated early pregnancy were immunostained with
antibodies for endothelial and proliferating cells. Number and distribution
of endothelial and proliferating cells were examined. Endothelial cells
were least abundant in the early luteal phase, increasing in the mid-luteal
phase (P < 0.03). Endothelial numbers did not differ significantly
between the late and the rescued corpora lutea. Endothelial cell
proliferation was greatest in the early luteal phase and continued at a
lower level during later stages. Simulated early pregnancy resulted in no
change in endothelial cell proliferation. These results showed that a high
degree of endothelial cell proliferation is associated with formation of
the human corpus luteum. Unchanging levels of proliferation following HCG
treatment (for 5-8 days from day 12 to day 16 post-ovulation, at 125 IU to
16,000 IU, following a daily doubling of dose) suggest that alternative
processes are involved during luteal rescue.
相似文献
17.
A. V. Semeikin V. M. Rzheznikov O. N. Minailova Ya. V. Dobrynin E. E. Mayatskaya 《Bulletin of experimental biology and medicine》1999,127(3):272-274
Antiproliferative effect of bis-β-chlorethylamine estrogen derivatives on human ovarian adenocarcinoma CaOV cells depends
on the dose of the drug. In concentrations of 10−5 and 5×10−6 M they inhibit, while in a dose of 5×10−7 M stimulate cell proliferation. It is assumed that CaOV cells express estradiol receptors. The interaction of these cytostatics
with estrogen-binding sites on CaOV cells is demonstrated.
Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 3, pp. 302–304, March, 1999 相似文献
18.
Michael Harrison Ronan P. Murphy Paul L. O’Connor Donal J. O’Gorman Noel McCaffrey Philip M. Cummins Niall M. Moyna 《European journal of applied physiology》2009,106(4):555-562
Triglyceride-rich postprandial
lipoproteins are known to activate endothelial cells in vitro,
contributing to atherosclerosis. Endothelial microparticles (EMP)
are membranous vesicles released into the circulation from vascular
endothelial cells that permit cell activation to be monitored
in vivo. The objective of the study was to examine changes in EMP
following a high fat meal, consumed with and without prior exercise.
Eight recreationally active young men underwent two oral fat
tolerance tests following either 100 min exercise at 70%
VO2peak
(EX trial) or no exercise (CON trial) on the previous evening.
Postprandial triglycerides were reduced
(1.97 ± 0.31 vs. 1.17 ± 0.13 mmol L−1,
p < 0.05) and HDL-cholesterol
(HDL-C) increased (1.20 ± 0.07 vs. 1.30 ± 0.08 mmol L−1,
p < 0.05) in the EX compared
to CON trial. EMP (CD31+/42b−) increased postprandially
(p < 0.05). However,
counts were not different between trials (postprandial CON and EX
trial counts × 103 μL−1,
3.10 ± 0.14 vs. 3.26 ± 0.37). There were no changes in sICAM-1 or
sVCAM-1 postprandially and no differences between trials.
Interleukin-6 (IL-6) and leukocytes increased postprandially
(p < 0.05). IL-6 values
were not different between trials. Leukocytes were higher at
0 h in the EX trial with CON and EX trial values similar at 6 h.
EMP, but not sICAM-1 or sVCAM-1, increase in response to a high
fat meal. However, EMP are not attenuated by acute exercise,
despite a considerable reduction in postprandial lipemia and
an increase in HDL-C.
M. Harrison and R. P. Murphy contributed equally to this work. 相似文献
19.
Membrane fragments from cultured endothelial cells for use in screening anti-FGF receptor antibodies
Subramaniam Venkateswaran Vincent D. Blanckaert Margaret E. Schelling 《Methods in Cell Science》1992,14(3):159-162
Summary Endothelial cell properties may be studied by either detecting their functional activity or immunologic reactivity. Antibodies against the fibroblast growth factor (FGF) receptor may help delineate signal transduction pathways involved in the proliferation of endothelial cells and angiogenesis. This paper describes membrane fragment preparation from cultured coronary venular endothelial cells for obtaining intact FGF receptors for the assay of the anti-receptor antibodies. 相似文献
20.
To study the effect of disturbed flow patterns on endothelial cells, the channels found within a modular tissue engineering
construct were reproduced in a microfluidic chip and lined with endothelial cells whose resulting phenotype under flow was
assessed using confocal microscopy. Modular tissue engineered constructs formed by the random packing of sub-millimetre, cylindrically
shaped, endothelial cell-covered modules into a larger container creates interconnected channels that permit the flow of fluids
such as blood. Due to the random packing, the flow path is tortuous and has the potential to create disturbed flow, resulting
in an activated endothelium. At an average shear stress of 2.8 dyn cm
−2, endothelial cells within channels of varying geometries showed higher amounts of activation, as evidenced by an increase
in ICAM-1 and VCAM-1 levels with respect to static controls. VE-cadherin expression also increased, however, it appeared discontinuous
around the perimeter of the cells. An increase in flow (15.6 dyn cm
−2) was sufficient to reduce ICAM-1 and VCAM-1 expression to a level below that of static controls for many disturbed flow-prone
channels that contained branches, curves, expansions and contractions. VE-cadherin expression was also reduced and became
discontinuous in all channels, possibly due to paracrine signaling. Other than showing a mild correlation to VE-cadherin,
which may be linked through a cAMP-initiated pathway, KLF2 was found to be largely independent of shear stress for this system.
To gauge the adhesiveness of the endothelium to leukocytes, THP-1 cells were introduced into flow-conditioned channels and
their attachment measured. Relative to static controls, THP-1 adhesion was reduced in straight and bifurcating channels. However,
even in the presence of flow, areas where multiple channels converged were found to be the most prone to THP-1 attachment.
The microfluidic system enabled a full analysis of the effect of the tortuous flow expected in a modular construct on endothelial
cell phenotype. 相似文献