scholarly journals The Combined Contribution of Vascular Endothelial Cell Migration and Adhesion to Stent Re-endothelialization

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaoli Wang ◽  
Fei Fang ◽  
Yinghao Ni ◽  
Hongchi Yu ◽  
Jia Ma ◽  
...  
Keyword(s):  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Mechanical Damage ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial ◽  
Stent Deployment ◽  
Stent Restenosis ◽  
Endothelial Denudation ◽  
And Migration

Coronary stent placement inevitably causes mechanical damage to the endothelium, leading to endothelial denudation and in-stent restenosis (ISR). Re-endothelialization depends mainly on the migration of vascular endothelial cells (VECs) adjacent to the damaged intima, as well as the mobilization and adhesion of circulating VECs. To evaluate the combined contribution of VEC migration and adhesion to re-endothelialization under flow and the influence of stent, in vitro models were constructed to simulate various endothelial denudation scales (2 mm/5 mm/10 mm) and stent deployment depths (flat/groove/bulge). Our results showed that (1) in 2 mm flat/groove/bulge models, both VEC migration and adhesion combined completed the percentage of endothelial recovery about 27, 16, and 12%, and migration accounted for about 21, 15, and 7%, respectively. It was suggested that the flat and groove models were in favor of VEC migration. (2) With the augmentation of the injury scales (5 and 10 mm), the contribution of circulating VEC adhesion on endothelial repair increased. Taken together, endothelial restoration mainly depended on the migration of adjacent VECs when the injury scale was 2 mm. The adhered cells contributed to re-endothelialization in an injury scale-dependent way. This study is helpful to provide new enlightenment for surface modification of cardiovascular implants.

CYLD regulates angiogenesis by mediating vascular endothelial cell migration

Blood ◽  
2010 ◽  
Vol 115 (20) ◽  
pp. 4130-4137 ◽  
Author(s):  
Jinmin Gao ◽  
Lei Sun ◽  
Lihong Huo ◽  
Min Liu ◽  
Dengwen Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Tube Formation ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial

Cylindromatosis (CYLD) is a deubiquitinase that was initially identified as a tumor suppressor and has recently been implicated in diverse normal physiologic processes. In this study, we have investigated the involvement of CYLD in angiogenesis, the formation of new blood vessels from preexisting ones. We find that knockdown of CYLD expression significantly impairs angiogenesis in vitro in both matrigel-based tube formation assay and collagen-based 3-dimensional capillary sprouting assay. Disruption of CYLD also remarkably inhibits angiogenic response in vivo, as evidenced by diminished blood vessel growth into the angioreactors implanted in mice. Mechanistic studies show that CYLD regulates angiogenesis by mediating the spreading and migration of vascular endothelial cells. Silencing of CYLD dramatically decreases microtubule dynamics in endothelial cells and inhibits endothelial cell migration by blocking the polarization process. Furthermore, we identify Rac1 activation as an important factor contributing to the action of CYLD in regulating endothelial cell migration and angiogenesis. Our findings thus uncover a previously unrecognized role for CYLD in the angiogenic process and provide a novel mechanism for Rac1 activation during endothelial cell migration and angiogenesis.

scholarly journals Immobilized DNA aptamers used as potent attractors for vascular endothelial cell: in vitro study of female rat

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Jung-Joon Cha ◽  
Hoyeon Lee ◽  
Miyoung Kim ◽  
Juyoung Kang ◽  
Hanlim Song ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Function ◽  
Therapeutic Potential ◽  
Vascular Endothelial Cells ◽  
Specific Binding ◽  
Vascular Endothelial Cell ◽  
Dna Aptamers ◽  
Female Rat ◽  
Vascular Endothelial

Abstract Vascular endothelial cells are essential to vascular function and maintenance. Dysfunction of these cells can lead to the development of cardiovascular disease or contribute to tumorigenesis. As such, the therapeutic modulation and monitoring of vascular endothelial cells are of significant clinical interest, and several endothelial-specific ligands have been developed for drug delivery and the monitoring of endothelial function. However, the application of these ligands has been limited by their high cost and tendency to induce immune responses, highlighting a need for alternate methods of targeting vascular endothelial cells. In the present study, we explore the therapeutic potential of DNA aptamers. Using cell-SELEX technology, we identified two aptamers with specific binding affinity for vascular endothelial cells and propose that these molecules show potential for use as new ligands for drug and biomarker research concerning vascular endothelial cells.

Estrogens modulate bovine vascular endothelial cell permeability and HSP 25 expression concomitantly

1998 ◽  
Vol 275 (3) ◽  
pp. H1011-H1015 ◽  
Author(s):  
F. Delarue ◽  
S. Daunes ◽  
R. Elhage ◽  
A. Garcia ◽  
F. Bayard ◽  
...  
Keyword(s):  
Vascular Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Vascular Endothelial Cell ◽  
Density Lipoprotein ◽  
Endothelial Permeability ◽  
Fluid Phase ◽  
Cell Permeability ◽  
Vascular Endothelial ◽  
Macromolecular Transport

The atheroprotective properties of estrogens are supported by clinical data from postmenopausal women who use estrogen replacement therapy. However, the mechanisms mediating activity remain unknown, and it has been suggested that estrogens may help to modulate endothelial permeability to atherogenic lipoproteins. In these studies we used bovine vascular endothelial cells as an in vitro model to show that estrogens were able to regulate low-density lipoprotein transport and permeability of the endothelial monolayer. Macromolecular transport was observed to be a second-order polynomial function of estrogen concentration. Moreover, this regulation was correlated with expression of heat shock protein (HSP) 25, which is known to influence fluid phase pinocytosis and cytoskeleton remodeling, thus suggesting a role for HSP 25 in the estrogenic control of transcellular permeability of the endothelium monolayer.

scholarly journals Biphasic Effect of Pirfenidone on Angiogenesis

2022 ◽  
Vol 12 ◽  
Author(s):  
Donghao Gan ◽  
Wenxiang Cheng ◽  
Liqing Ke ◽  
Antonia RuJia Sun ◽  
Qingyun Jia ◽  
...  
Keyword(s):  
Vascular Endothelial Cells ◽  
Tube Formation ◽  
Endothelial Cell Migration ◽  
High Concentration ◽  
Low Concentrations ◽  
Biphasic Effect ◽  
High Concentrations ◽  
And Migration ◽  
The Impact

Pirfenidone (PFD), a synthetic arsenic compound, has been found to inhibit angiogenesis at high concentrations. However, the biphasic effects of different PFD concentrations on angiogenesis have not yet been elucidated, and the present study used an in vitro model to explore the mechanisms underlying this biphasic response. The effect of PFD on the initial angiogenesis of vascular endothelial cells was investigated through a Matrigel tube formation assay, and the impact of PFD on endothelial cell migration was evaluated through scratch and transwell migration experiments. Moreover, the expression of key migration cytokines, matrix metalloproteinase (MMP)-2 and MMP-9, was examined. Finally, the biphasic mechanism of PFD on angiogenesis was explored through cell signaling and apoptosis analyses. The results showed that 10–100 μM PFD has a significant and dose-dependent inhibitory effect on tube formation and migration, while 10 nM–1 μM PFD significantly promoted tube formation and migration, with 100 nM PFD having the strongest effect. Additionally, we found that a high concentration of PFD could significantly inhibit MMP-2 and MMP-9 expression, while low concentrations of PFD significantly promoted their expression. Finally, we found that high concentrations of PFD inhibited EA.hy926 cell tube formation by promoting apoptosis, while low concentrations of PFD promoted tube formation by increasing MMP-2 and MMP-9 protein expression predominantly via the EGFR/p-p38 pathway. Overall, PFD elicits a biphasic effect on angiogenesis through different mechanisms, could be used as a new potential drug for the treatment of vascular diseases.

scholarly journals Zeb1 promotes corneal neovascularization by regulation of vascular endothelial cell proliferation

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Lei Jin ◽  
Yingnan Zhang ◽  
Wei Liang ◽  
Xiaoqin Lu ◽  
Niloofar Piri ◽  
...  
Keyword(s):  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Intrinsic Factor ◽  
Corneal Neovascularization ◽  
Endothelial Cell Proliferation ◽  
Vascular Endothelial ◽  
Independent Mechanism ◽  
Antiangiogenic Factors ◽  
And Migration ◽  
Proliferation And Migration

AbstractAngiogenesis is required for tissue repair; but abnormal angiogenesis or neovascularization (NV) causes diseases in the eye. The avascular status in the cornea is a prerequisite for corneal clarity and thought to be maintained by the equilibrium between proangiogenic and antiangiogenic factors that controls proliferation and migration of vascular endothelial cells (ECs) sprouting from the pericorneal plexus. VEGF is the most important intrinsic factor for angiogenesis; anti-VEGF therapies are available for treating ocular NV. However, the effectiveness of the therapies is limited because of VEGF-independent mechanism(s). We show that Zeb1 is an important factor promoting vascular EC proliferation and corneal NV; and a couple of small molecule inhibitors can evict Ctbp from the Zeb1–Ctbp complex, thereby reducing EC Zeb1 expression, proliferation, and corneal NV. We conclude that Zeb1-regulation of angiogenesis is independent of Vegf and that the ZEB1–CtBP inhibitors can be of potential therapeutic significance in treating corneal NV.

Vascular endothelial cell lineage-specific promoter in transgenic mice

Development ◽  
1995 ◽  
Vol 121 (4) ◽  
pp. 1089-1098 ◽  
Author(s):  
T.M. Schlaeger ◽  
Y. Qin ◽  
Y. Fujiwara ◽  
J. Magram ◽  
T.N. Sato
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Vascular Endothelial Cells ◽  
Es Cells ◽  
Vascular Endothelial Cell ◽  
Cell Lineage ◽  
Vascular Endothelial ◽  
Lacz Reporter

Vascular endothelial cells play essential roles in the function and development of the cardiovascular system. However, due to the lack of lineage-specific markers suitable for molecular and biochemical analyses, very little is known about the molecular mechanisms that regulate endothelial cell differentiation. We report the first vascular endothelial cell lineage-specific (including angioblastic precursor cells) 1.2 kb promoter in transgenic mice. Moreover, deletion analysis of this promoter region in transgenic embryos revealed multiple elements that are required for the maximum endothelial cell lineage-specific expression. This is a powerful molecular tool that will enable us to identify factors and cellular signals essential for the establishment of vascular endothelial cell lineage. It will also allow us to deliver genes specifically into this cell type in vivo to test specifically molecules that have been implicated in cardiovascular development. Furthermore, we have established embryonic stem (ES) cells from the blastocysts of the transgenic mouse that carry the 1.2 kb promoter-LacZ reporter transgene. These ES cells were able to differentiate in vitro to form cystic embryoid bodies (CEB) that contain endothelial cells determined by PECAM immunohistochemistry. However, these in vitro differentiated endothelial cells did not express the LacZ reporter gene. This indicates the lack of factors and/or cellular interactions which are required to induce the expression of the reporter gene mediated by this 1.2 kb promoter in this in vitro differentiation system. Thus this system will allow us to screen for the putative inducers that exist in vivo but not in vitro. These putative inducers are presumably important for in vivo differentiation of vascular endothelial cells.

scholarly journals The vascular endothelial cell-expressed prion protein doppel promotes angiogenesis and blood-brain barrier development

Development ◽  
2020 ◽  
Vol 147 (18) ◽  
pp. dev193094
Author(s):  
Zhihua Chen ◽  
John E. Morales ◽  
Naze Avci ◽  
Paola A. Guerrero ◽  
Ganesh Rao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Blood Vessel ◽  
Prion Protein ◽  
Tyrosine Kinases ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
And Migration ◽  
Migration Analysis

ABSTRACTThe central nervous system (CNS) contains a complex network of blood vessels that promote normal tissue development and physiology. Abnormal control of blood vessel morphogenesis and maturation is linked to the pathogenesis of various neurodevelopmental diseases. The CNS-specific genes that regulate blood vessel morphogenesis in development and disease remain largely unknown. Here, we have characterized functions for the gene encoding prion protein 2 (Prnd) in CNS blood vessel development and physiology. Prnd encodes the glycosylphosphatidylinositol (GPI)-linked protein doppel, which is expressed on the surface of angiogenic vascular endothelial cells, but is absent in quiescent endothelial cells of the adult CNS. During CNS vascular development, doppel interacts with receptor tyrosine kinases and activates cytoplasmic signaling pathways involved in endothelial cell survival, metabolism and migration. Analysis of mice genetically null for Prnd revealed impaired CNS blood vessel morphogenesis and associated endothelial cell sprouting defects. Prnd−/− mice also displayed defects in endothelial barrier integrity. Collectively, these data reveal novel mechanisms underlying doppel control of angiogenesis in the developing CNS, and may provide new insights about dysfunctional pathways that cause vascular-related CNS disorders.

scholarly journals Capsule protects against intracellular killing and enables vascular endothelial cell translocation during invasive pneumococcal disease

2021 ◽  
Author(s):  
Terry Brissac ◽  
Eriel Martínez ◽  
Katherine L. Kruckow ◽  
Ashleigh N. Riegler ◽  
Feroze Ganaie ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Vascular Endothelial Cells ◽  
Survival Rates ◽  
Antioxidant Properties ◽  
Vascular Endothelial Cell ◽  
Invasive Disease ◽  
Vascular Endothelial ◽  
Virulence Determinants

ABSTRACTStreptococcus pneumoniae (Spn) is a leading cause of invasive disease. Chief among its virulence determinants is capsular polysaccharide which protects the bacterium from phagocytosis. While 100 antigenically distinct capsule types are produced by Spn, i.e. serotypes, only 20-30 are commonly associated with invasive disease. A frequency that suggests serotypespecific properties of the capsule influence virulence. Herein, we show capsule has strong antioxidant properties. Moreover, that this property promotes invasive disease by protecting Spn taken up by vascular endothelial cells during bacteremia from endosome-killing and enhancing the translocation rate into organs. Crucially, isogenic capsule-switch mutants of Spn varied considerably in their resistance to H2O2-killing in culture and measured levels correlated positively with intracellular survival rates in vitro, organ invasion rates in vivo, and epidemiologically-established human attack rates for the corresponding serotype. The amount of capsule produced and specific biochemical features of a serotype, such as acetylation, also influenced Spn resistance to oxidative stress. Autolysin-mediated shedding was also found to be necessary, indicating that capsule worked as a distal sink for reactive oxygen species. Our results outline a new role for capsular polysaccharide, as an intracellular antioxidant. They help to explain why certain serotypes of Spn have greater propensity for human disease.

scholarly journals Flt-1 regulates vascular endothelial cell migration via a protein tyrosine kinase-7–dependent pathway

Blood ◽  
2011 ◽  
Vol 117 (21) ◽  
pp. 5762-5771 ◽  
Author(s):  
Hyung Keun Lee ◽  
Sunil K. Chauhan ◽  
EunDuk Kay ◽  
Reza Dana
Keyword(s):  
Endothelial Cells ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Vascular Endothelial Cell ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial ◽  
Protein Tyrosine ◽  
Protein Tyrosine Kinase 7

Abstract Protein tyrosine kinase 7 (PTK7) is a pseudokinase whose precise function in regulating angiogenesis remains unknown. The purpose of this study was to define the mechanisms by which PTK7 promotes vascular endothelial growth factor-A (VEGF-A)–induced angiogenesis in vivo and in vitro. Immunoblotting was used to measure PTK7 expression in several types of vascular endothelial cells. Using both immunoprecipitation and immunoblotting, PTK7 was found to join a receptor complex with Flt-1 (VEGFR1), but not with KDR/Flk-1 (VEGFR2) or with Flt-4 (VEGFR3). By surface plasmon resonance analysis, the interaction between Flt-1 and PTK7 was confirmed and found to be intensified by VEGF-A. Flt-1 phosphorylation and downstream signals of Akt, and focal adhesion kinase (FAK) thus induced were down-regulated by inhibition of PTK7 expression using siRNA. Moreover, PTK7 overexpression in endothelial cells resulted in enhanced angiogenesis in vitro. In contrast, neovascularization induced in vivo by VEGF-A pellets was significantly decreased by injection of siRNA targeting PTK7. These data suggest that PTK7 serves an essential role in Flt-1–mediated angiogenesis.

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