scholarly journals Axl Is Essential for in-vitro Angiogenesis Induced by Vitreous From Patients With Proliferative Diabetic Retinopathy

2021 ◽  
Vol 8 ◽  
Author(s):  
Wenyi Wu ◽  
Huizuo Xu ◽  
Zhishang Meng ◽  
Jianxi Zhu ◽  
Siqi Xiong ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Tyrosine Kinases ◽  
Vascular Endothelial Cells ◽  
Specific Inhibitor ◽  
Cell Types ◽  
Specific Protein ◽  
Vascular Endothelial

Proliferative diabetic retinopathy (PDR), characterized mainly with abnormal epiretinal angiogenesis forming fibrovascular membranes (FVMs), threatens vision of people with diabetes; FVMs consist of extracellular matrix and a variety of cell types including vascular endothelial cells. Axl, one of receptor tyrosine kinases, can be activated indirectly by vascular endothelial growth factor-A (VEGF-A) via an intracellular route for promoting angiogenesis. In this study, we revealed that growth arrest-specific protein 6 (Gas6), a specific ligand of Axl, was elevated in vitreous from patients with PDR and that Axl was activated in FVMs from patients with PDR. In addition, we demonstrated that in cultured human retinal microvascular endothelial cells (HRECs), Axl inhibition via suppression of Axl expression with Clustered Regularly Interspaced Short Palindromic Repeats/ CRISPR-associated protein 9 or through inactivation with its specific inhibitor R428 blocked PDR vitreous-induced Akt activation and proliferation of HRECs. Furthermore, PDR vitreous-heightened migration and tube formation of HRECs were also blunted by restraining Axl. These results indicate that in the pathogenesis of PDR, Axl can be activated by Gas6 binding directly and by VEGF-A via an intracellular route indirectly, suggesting that Axl plays a pivotal role in the development of PDR and that Axl inhibition shows a bright promise for PDR therapy.

Origin and diversity of embryonic endothelium/endocardium

2018 ◽  
Author(s):  
LeShana SaintJean ◽  
H.S. Baldwin
Keyword(s):  
Endothelial Cells ◽  
Heart Development ◽  
Vascular Endothelial Cells ◽  
Coronary Vessels ◽  
Cell Types ◽  
Genetic Profile ◽  
Vascular Endothelial ◽  
Tremendous Progress

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.

Prostacyclin: Production by Vascular Endothelium and Effects on Platelet Aggregation

1979 ◽  
Author(s):  
S. Moncada ◽  
S. Bunting
Keyword(s):  
Endothelial Cells ◽  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Vascular Endothelium ◽  
Vascular Endothelial Cells ◽  
Specific Inhibitor ◽  
Inhibitory Effect ◽  
Vascular Endothelial ◽  
Prostacyclin Production

The inhibitory effect of vascular endothelial cells on platelet aggregation is due to their ability to release prostacyclin. The existence of an ADPase has been confirmed in endothelial cells but this enzymes does not seem to be related to the anti-aggregating properties of vascular endothelium. In vitro, the release of prostacyclin by humand and rabbit endothelial cells persists after several subcultures. The production of PGI2 can be demonstrated by its inhibition by aspirin-like drugs or 15-hydroperoxy arachidonic acid (a specific inhibitor of PGI2 synthesis). Moreover, the antiaggregating activity is antagonised by an antibody to 5,6 dihydro prostacyclin which cross reacts and neutralises prostacyclin.

Morphilogy and Ultrastructure of in Vitro Cultures of Aortic Endothelial Cells Interacting with Antibodies

1979 ◽  
Author(s):  
S. Korach ◽  
D. Ngo
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Vascular Endothelial Cells ◽  
Intercellular Junctions ◽  
Cell Types ◽  
Endothelial Damage ◽  
Antibody Concentration ◽  
High Yields ◽  
Scanning Em

Adult pig aortas, sectioned longitudinally, were incubated in 0.1% collagenase-PBS (15 mn, 37°C). Gentle scraping of the lumenal surface resulted in high yields (3-4 x 106 cell/aorta) of viable endothelial cells, essentially devoid of other cell types by morphological and immunochemical (F VIII-antigen) criteria. Confluent monolayers were incubated for various times (5 mn to 1 wk) with decomplemented rabbit antisera raised against pig endothelial cells. Changes in cell morphology appeared to depend on antibody concentration rather than on duration of contact with antiserum. High concentrations of antiserum (5 to 20%) led to cytoplasmic shredding, bulging of cells and extensive vacuolization, whereas at lower concentrations, cells appeared almost normal. Transmission EM studies by the indirect immunoperoxydase method showed antibodies reacting with unfixed cells to be distributed all over the upper cell surface, in the outer parts of intercellular junctions, and within numerous pinocytotic vesicles. Much weaker reactions could also be seen at the lower cell surface. When viewed under the Scanning EM, antiserum-treated endothelial cells also disclosed antibody concentration-dependent bulging and release of cells from their substrate. In vitro studies of gradual modifications of vascular endothelial cells acted upon by antibodies should provide a better understanding of the structural and biochemical processes underlying endothelial damage and detachment.

scholarly journals Synthesis and physiological activity of heterodimers comprising different splice forms of vascular endothelial growth factor and placenta growth factor

1996 ◽  
Vol 316 (3) ◽  
pp. 703-707 ◽  
Author(s):  
Ralf BIRKENHÄGER ◽  
Bernard SCHNEPPE ◽  
Wolfgang RÖCKL ◽  
Jörg WILTING ◽  
Herbert A. WEICH ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Vascular Endothelial Cells ◽  
Physiological Activity ◽  
Expression System ◽  
Vascular Endothelial ◽  
Placenta Growth Factor ◽  
Splice Forms

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.

scholarly journals Regulation of capillary tubules and lipid formation in vascular endothelial cells and macrophages via extracellular vesicle-mediated microRNA-4306 transfer

2018 ◽  
Vol 47 (1) ◽  
pp. 453-469 ◽  
Author(s):  
Ying Yang ◽  
Hui Luo ◽  
Can Zhou ◽  
Rongyi Zhang ◽  
Si Liu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Vascular Endothelial Cells ◽  
Density Lipoprotein ◽  
Extracellular Vesicle ◽  
Luciferase Reporter ◽  
Vascular Endothelial ◽  
Human Coronary Artery ◽  
Lipid Formation

Objective This study aimed to examine regulation of capillary tubules and lipid formation in vascular endothelial cells and macrophages via extracellular vesicle-mediated microRNA (miRNA)-4306 transfer Methods Whole blood samples (12 mL) were collected from 53 patients, and miR-4306 levels in extracellular vesicles (EVs) were analyzed by reverse transcription-polymerase chain reaction. Human coronary artery vascular endothelial cells (HCAECs) and human monocyte-derived macrophages (HMDMs) were transfected with a scrambled oligonucleotide, an miR-4306 mimic, or an anti-miR-4306 inhibitor. The direct effect of miR-4306 on the target gene was analyzed by a dual-luciferase reporter assay. Results EV-contained miR-4306 released from HMDMs was significantly upregulated in coronary artery disease. Oxidized low-density lipoprotein (ox-LDL)-stimulated HMDM-derived EVs inhibited proliferation, migration, and angiogenesis abilities of HCAECs in vitro. However, ox-LDL-stimulated HCAEC-derived EVs enhanced lipid formation of HMDMs. The possible mechanism of these findings was partly due to EV-mediated miR-4306 upregulation of the Akt/nuclear factor kappa B signaling pathway. Conclusions Paracrine cellular crosstalk between HCAECs and HMDMs probably supports the pro-atherosclerotic effects of EVs under ox-LDL stress.

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