scholarly journals Choline Phospholipid Metabolites of Human Vascular Endothelial Cells Altered by Cyclooxygenase Inhibition, Growth Factor Depletion, and Paracrine Factors Secreted by Cancer Cells

2003 ◽  
Vol 2 (2) ◽  
pp. 153535002003031
Author(s):  
Noriko Mori ◽  
Kshama Natarajan ◽  
V. P. Chacko ◽  
Dmitri Artemov ◽  
Zaver M. Bhujwalla

Magnetic resonance studies have previously shown that solid tumors and cancer cells in culture typically exhibit high phosphocholine and total choline. Treatment of cancer cells with the anti-inflammatory agent, indomethacin (INDO), reverted the phenotype of choline phospholipid metabolites in cancer cells towards a less malignant phenotype. Since endothelial cells form a key component of tumor vasculature, in this study, we used MR spectroscopy to characterize the phenotype of choline phospholipid metabolites in human umbilical vein endothelial cells (HUVECs). We determined the effect of growth factors, the anti-inflammatory agent INDO, and conditioned media obtained from a malignant cell line, on choline phospholipid metabolites. Growth factor depletion or treatment with INDO induced similar changes in the choline phospholipid metabolites of HUVECs. Treatment with conditioned medium obtained from MDA-MB-231 cancer cells induced changes similar to the presence of growth factor supplements. These results suggest that cancer cells secrete growth factors and/or other molecules that influence the choline phospholipid metabolism of HUVECs. The ability of INDO to alter choline phospholipid metabolism in the presence of growth factor supplements suggests that the inflammatory response pathways of HUVECs may play a role in cancer cell-HUVEC interaction and in the response of HUVECs to growth factors.

1978 ◽  
Vol 77 (3) ◽  
pp. 774-788 ◽  
Author(s):  
D Gospodarowicz ◽  
KD Brown ◽  
CR Birdwell ◽  
BR Zetter

Because the response of human endothelial cells to growth factors and conditioning agents has broad implications for our understanding of wound healing angiogenesis, and human atherogenesis, we have investigated the responses of these cells to the fibroblast (FGF) and epidermal growth factors (EGF), as well as to the protease thrombin, which has been previously shown to potentiate the growth response of other cell types of FGF and EGF. Because the vascular endothelial cells that form the inner lining of blood vessels may be expected to be exposed to high thrombin concentrations after trauma or in pathological states associated with thrombosis, they are of particular interest with respect to the physiological role of this protease in potentiating cell proliferation. Our results indicate that human vascular endothelial cells respond poorly to either FGF or thrombin alone. In contrast, when cells are maintained in the presence of thrombin, their proliferative response to FGF is greatly increased even in cultures seeded at a density as low as 3 cells/mm2. Human vascular endothelial cells also respond to EGF and thrombin, although their rate of proliferation is much slower than when maintained with FGF and thrombin. In contrast, bovine vascular endothelial cells derived from vascular territories as diverse as the bovine heart, aortic arch, and umbilical vein respond maximally to FGF alone and neither respond to nor bind EGF. Furthermore, the response of bovine vascular endothelial cells to FGF was not potentiated by thrombin, indicating that the set of factors controlling the proliferation of vascular endothelial cells could be species-dependent. The requirement of cultured human vascular endothelial cells for thrombin could explain why the human cells, in contrast to bovine endothelial cells, are so difficult to maintain in tissue culture. Our results demonstrate that by using FGF and thrombin one can develop cultures of human vascular endothelial cells capable of being passage repeatedly while maintaining a high mitotic index. The stock cultures used for these studies have been passed weekly with a split ratio of 1 to 10 and are currently in their 30th passage. These cultures are indistinguishable from earlier passages when examined for the presence of Weibel-Palade bodies or Factor VIII antigen. We conclude that the use of FGF and thrombin can prevent the precocious senescence observed in most human endothelial cells cultures previously described.


2021 ◽  
pp. 039139882110431
Author(s):  
Andreas Groger ◽  
Ioannis-Fivos Megas ◽  
Ernst Magnus Noah ◽  
Norbert Pallua ◽  
Gerrit Grieb

In general, matrices for tissue engineering must maintain structural integrity during the process of tissue formation and promote vascularization of developing tissue. Therefore, collagen sponges, manufactured by an approach that offers the potential of unidirectional pore size, were seeded with human umbilical vein endothelial cells (HUVEC) to demonstrate a positive effect on cell proliferation. In addition, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have been used to promote proliferation of HUVEC on optimized collagen sponges. Growth and viability of the cells were evaluated. Potential unidirectional pore structure demonstrated an improvement of both, endothelial cell growth and viability. Supplementation of growth factors showed an additional increase of endothelial cell growth on collagen sponges, which confirmed the high potential of combining this biomaterial with growth factors. The results suggest that a collagen sponge with a potential specific pore size could be a suitable scaffold for endothelial cells and might be a promising implantable biomaterial with enhanced angiogenic capabilities for future clinical applications.


2019 ◽  
Vol 17 (4) ◽  
pp. 379-387 ◽  
Author(s):  
Yan Sun ◽  
Xiao-li Liu ◽  
Dai Zhang ◽  
Fang Liu ◽  
Yu-jing Cheng ◽  
...  

Background:Intraplaque angiogenesis, the process of generating new blood vessels mediated by endothelial cells, contributes to plaque growth, intraplaque hemorrhage, and thromboembolic events. Platelet-derived Exosomes (PLT-EXOs) affect angiogenesis in multiple ways. The ability of miR-126, one of the best-characterized miRNAs that regulates angiogenesis, carried by PLT-EXOs to influence angiogenesis via the regulation of the proliferation and migration of endothelial cells is unknown. In this study, we aimed to investigate the effects of PLT-EXOs on angiogenesis by Human Umbilical Vein Endothelial Cells (HUVECs).Methods:We evaluated the levels of miR-126 and angiogenic factors in PLT-EXOs from Acute Coronary Syndrome (ACS) patients and healthy donors by real-time Polymerase Chain Reaction (PCR) and western blotting. We incubated HUVECs with PLT-EXOs and measured cell proliferation and migration with the Cell Counting Kit-8 assay and scratch assay, respectively. We also investigated the expression of miR-126 and angiogenic factors in HUVECs after exposure to PLT-EXOs by western blotting and real-time PCR.Results:PLT-EXOs from ACS patients contained higher levels of miR-126 and angiogenic factors, including Vascular Endothelial Growth Factor (VEGF), basic Fibroblast Growth Factor (bFGF), and Transforming Growth Factor Beta 1 (TGF-β1), than those from healthy donors (p<0.05). Moreover, the levels of exosomal miR-126 and angiogenic factors were increased after stimulation with thrombin (p<0.01). HUVEC proliferation and migration were promoted by treatment with activated PLT-EXOs (p<0.01); they were accompanied by the over-expression of miR-126 and angiogenic factors, including VEGF, bFGF, and TGF-β1 (p<0.01).Conclusion:Activated PLT-EXOs promoted the proliferation and migration of HUVECs, and the overexpression of miR-126 and angiogenic factors, thereby elucidating potential new therapeutic targets for intraplaque angiogenesis.


2021 ◽  
Vol 9 ◽  
pp. 205031212110268
Author(s):  
Samar Sultan

Objectives: This study reports the levels of cytokines, chemokines, and growth factors previously identified as taking part in the pathology of atherosclerosis in human umbilical vein endothelial cells derived from mothers with type 2 diabetes and compares them with those in human umbilical vein endothelial cells derived from healthy mothers under normal glucose conditions. Methods: Cytokine analysis measures of human umbilical vein endothelial cell lysates were obtained using a multiple analyte profiling (xMAP) assay based on magnetic bead-based technology, using the MAGPIX instrument. The correlation between cytokines, chemokines, and growth factors was examined statistically in human umbilical vein endothelial cells derived from mothers with type 2 diabetes. Results: This study showed that the expression of proinflammatory cytokine interleukin-1 alpha was significantly greater in human umbilical vein endothelial cells derived from mothers with type 2 diabetes than those derived from healthy mothers. The protein level of granulocyte colony-stimulating factor was higher in human umbilical vein endothelial cells derived from mothers with type 2 diabetes than those derived from healthy mothers. A significant positive correlation was demonstrated between the protein expression of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in human umbilical vein endothelial cells derived from mothers with type 2 diabetes. Conclusion: Diabetes evokes a persistent inflammatory phenotype in human umbilical vein endothelial cells, as indicated by the enhanced production of cytokines and growth factors under normal glucose conditions.


Sign in / Sign up

Export Citation Format

Share Document