Interaction between vascular endothelial cells and vascular intimal spindle-shaped cells in vitro

1983 ◽  
Vol 60 (1) ◽  
pp. 89-102
Author(s):  
D de Bono ◽  
C. Green

The interactions between human or bovine vascular endothelial cells and fibroblast-like vascular intimal spindle-shaped cells have been studied in vitro, using species-specific antibodies to identify the different components in mixed cultures. Pure cultures of endothelial cells grow as uniform, nonoverlapping monolayers, but this growth pattern is lost after the addition of spindle cells, probably because the extracellular matrix secreted by the latter causes the endothelial cells to modify the way they are attached to the substrate. The result is a network of tubular aggregates of endothelial cells in a three-dimensional ‘polylayer’ of spindle-shaped cells. On the other hand, endothelial cells added to growth-inhibited cultures of spindle-shaped cells will grow in sheets over the surface of the culture. Human endothelial cells grown in contact with spindle-shaped cells have a reduced requirement for a brain-derived endothelial growth factor. The interactions of endothelial cells and other connective tissue cells in vitro may be relevant to the mechanisms of endothelial growth and blood vessel formation in vivo, and emphasize the potential importance of extracellular matrix in controlling endothelial cell behaviour.

Author(s):  
Lowell Taylor Edgar ◽  
James E. Guilkey ◽  
Clayton J. Underwood ◽  
Brenda Baggett ◽  
Urs Utzinger ◽  
...  

The process of angiogenesis is regulated by both chemical and mechanical signaling. While the role of chemical factors such as vascular endothelial growth factor (VEGF) during angiogenesis has been extensively studied, the influence of the mechanostructural environment on new vessel generation has received significantly less attention. During angiogenesis, endothelial cells in the existing vasculature detach and migrate out into the surrounding extracellular matrix (ECM), forming tubular structures that eventually mature into new blood vessels. This process is modulated by the structure and composition of the ECM [1]. The ECM is then remodeled by endothelial cells in the elongating neovessel tip, resulting in matrix condensation and changes in fiber orientation [2]. The mechanism as to how angiogenic vasculature and the ECM influence each other is poorly understood.


2014 ◽  
Vol 1623 ◽  
Author(s):  
Frances D. Liu ◽  
Adam S. Zeiger ◽  
Krystyn J. Van Vliet

ABSTRACTInteractions between biological cells and surrounding extracellular matrix (ECM) materials modulate many cell behaviors including adhesion and migration. One key example of this cellmatrix reciprocity is in the context of angiogenesis, the sprouting of new blood vessels from preexisting vasculature. Vascular endothelial cells (VECs) create and remodel the ECM during this process. In vivo, the surrounding fluid environment includes high concentrations of macromolecules, and is considered “crowded” in comparison to in vitro environments. Here, we quantified the amount and organization of collagen IV, a prominent ECM component of VECs, that was produced by these cells over four weeks in vitro in the presence or absence of macromolecular crowder (MMC) nanoparticles that approximated in vivo crowding. In the presence of MMCs, the amount and degree of alignment of collagen IV was greater. This ECM difference emerged within one week and was sustained for over four weeks. We explored the effect of initial cell density (cells/µm2) on this matrix production, to consider potential differences at a wound site versus an intact vessel. Moreover, we found the biophysical effect of MMCs to be unmodulated by secretions from an adjacent cell type in microvessels (pericytes). These results suggest that macromolecular crowding plays a direct role in remodeling the basement membrane, and that such crowding can be induced in vitro to more closely approximate the cell microenvironment.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Juliete A. F. Silva ◽  
Xiaoping Qi ◽  
Maria B. Grant ◽  
Michael E. Boulton

AbstractThe vascular endothelial growth factor receptors (VEGFRs) can shape the neovascular phenotype of vascular endothelial cells when translocated to the nucleus, however the spatial and temporal changes in the intracellular distribution and translocation of VEGFRs to the nucleus and the organelles involved in this process is unclear. This study reports the effect of exogenous VEGF on translocation of VEGFRs and organelles in micro- and macrovascular endothelial cells. We showed that VEGF is responsible for: a rapid and substantial nuclear translocation of VEGFRs; VEGFR1 and VEGFR2 exhibit distinct spatial, temporal and structural translocation characteristics both in vitro and in vivo and this determines the nuclear VEGFR1:VEGFR2 ratio which differs between microvascular and macrovascular cells; VEGFR2 nuclear translocation is associated with the endosomal pathway transporting the receptor from Golgi in microvascular endothelial cells; and an increase in the volume of intracellular organelles. In conclusion, the nuclear translocation of VEGFRs is both receptor and vessel (macro versus micro) dependent and the endosomal pathway plays a key role in the translocation of VEGFRs to the nucleus and the subsequent export to the lysosomal system. Modulating VEGF-mediated VEGFR1 and VEGFR2 intracellular transmigration pathways may offer an alternative for the development of new anti-angiogenic therapies.


1996 ◽  
Vol 316 (3) ◽  
pp. 703-707 ◽  
Author(s):  
Ralf BIRKENHÄGER ◽  
Bernard SCHNEPPE ◽  
Wolfgang RÖCKL ◽  
Jörg WILTING ◽  
Herbert A. WEICH ◽  
...  

Vascular endothilial growth factor (VEGF) and placenta growth factor (PIGF) are members of a dimeric-growth-factor family with angiogenic properties. VEGF is a highly potent and specific mitogen for endothelial cells, playing a vital role in angiogenesis in vivo. The role of PIGF is less clear. We expressed the monomeric splice forms VEGF-165, VEGF-121, PIGF-1 and PlGF-2 as unfused genes in Escherichia coli using the pCYTEXP expression system. In vitro dimerization experiments revealed that both homo- and hetero-dimers can be formed from these monomeric proteins. The dimers were tested for their ability to promote capillary growth in vivo and stimulate DNA synthesis in cultured human vascular endothelial cells. Heterodimers comprising different VEGF splice forms, or combinations of VEGF/PlGF splice forms, showed mitogenic activity. The results demonstrate that four different heterodimeric growth factors are likely to have as yet uncharacterized functions in vivo.


Blood ◽  
2010 ◽  
Vol 115 (20) ◽  
pp. 4130-4137 ◽  
Author(s):  
Jinmin Gao ◽  
Lei Sun ◽  
Lihong Huo ◽  
Min Liu ◽  
Dengwen Li ◽  
...  

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.


Author(s):  
LeShana SaintJean ◽  
H.S. Baldwin

The endocardium represents a distinct population of endothelial cells that arises during the initiation of heart development. Endocardial cells can easily be distinguished from most of the other cardiac cell types. However, endocardial and vascular endothelial cells contain a similar genetic profile that limits the ability to study each group independently. Despite these limitations, tremendous progress has been made in identifying the different roles of endocardial cells throughout heart development. Initial studies focused on the origin of endocardial cells and their role in valvulogenesis, trabeculation, and formation of the ventricular and atrial septum. With the advancement of microscopy and the availability of endocardial specific reporter models (in vitro and in vivo) we have obtained more insight into the molecular, structural, and functional complexity of the endocardium. Additional studies have demonstrated how the endocardium is also involved in the development of coronary vessels within the compact myocardium and in heart regeneration.


2017 ◽  
Vol 38 (5) ◽  
pp. 3153-3159 ◽  
Author(s):  
Xinwen Wang ◽  
Weifeng Xu ◽  
Shenglin Wang ◽  
Feqiang Yu ◽  
Jinyi Feng ◽  
...  

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