scholarly journals Control of proliferation of human vascular endothelial cells. Characterization of the response of human umbilical vein endothelial cells to fibroblast growth factor, epidermal growth factor, and thrombin

1978 ◽  
Vol 77 (3) ◽  
pp. 774-788 ◽  
Author(s):  
D Gospodarowicz ◽  
KD Brown ◽  
CR Birdwell ◽  
BR Zetter
Keyword(s):  
Endothelial Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Physiological Role ◽  
Cell Types ◽  
Vascular Endothelial ◽  
Human Endothelial Cells ◽  
Epidermal Growth

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.

Epidermal Growth Factor Stimulates Prostacyclin Production by Cultured Human Vascular Endothelial Cells

1988 ◽  
Vol 59 (02) ◽  
pp. 248-250 ◽  
Author(s):  
Ari Ristimäki ◽  
Olavi Ylikorkala ◽  
Jaakko Perheentupa ◽  
Lasse Viinikka
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Fold Increase ◽  
Protein Synthesis Inhibitor ◽  
Vascular Endothelial ◽  
Synthesis Inhibitor ◽  
Epidermal Growth

SummaryEpidermal growth factor (EGF) stimulated prostacyclin (PGI2) production by cultured human umbilical vein endothelial cells, as measured by radioimmunoassay of its stable metabolite 6-keto- prostaglandin Flα. This effect of EGF was dose-dependent, the lowest stimulatory concentration of EGF was 1.0 ng/ml and 100 ng/ml caused a 2.7 ± 0.3 (mean ± SEM) fold increase in the PGI2 synthesis. The stimulation appeared at 3-6 h of incubation and lasted at least 24 h. It was suppressed by EGF antibodies and blocked by protein synthesis inhibitor cycloheximide. Cells preincubated 12 h with EGF released also higher amounts of PGI2when incubated with thrombin for 5 min. It is concluded that EGF liberated from platelets during aggregation may prevent local thrombogenesis and atherogenesis by stimulating the release of the antiaggregatory, vasodilatory PGI2 from vascular endothelial cells.

scholarly journals The ATF6-EGF Pathway Mediates the Awakening of Slow-Cycling Chemoresistant Cells and Tumor Recurrence by Stimulating Tumor Angiogenesis

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1772
Author(s):  
Jaebeom Cho ◽  
Hye-Young Min ◽  
Honglan Pei ◽  
Xuan Wei ◽  
Jeong Yeon Sim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cancer Cells ◽  
Tumor Recurrence ◽  
Vascular Endothelial Cells ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Epidermal Growth ◽  
Slow Cycling

Slow-cycling cancer cells (SCCs) with a quiescence-like phenotype are believed to perpetrate cancer relapse and progression. However, the mechanisms that mediate SCC-derived tumor recurrence are poorly understood. Here, we investigated the mechanisms underlying cancer recurrence after chemotherapy, focusing on the interplay between SCCs and the tumor microenvironment. We established a preclinical model of SCCs by exposing non-small-cell lung cancer (NSCLC) cells to either the proliferation-dependent dye carboxyfluorescein diacetate succinimidyl ester (CFSE) or chemotherapeutic drugs. An RNA sequencing analysis revealed that the established SCCs exhibited the upregulation of a group of genes, especially epidermal growth factor (EGF). Increases in the number of vascular endothelial growth factor receptor (VEGFR)-positive vascular endothelial cells and epidermal growth factor receptor (EGFR) activation were found in NSCLC cell line- and patient-derived xenograft tumors that progressed upon chemotherapy. EGFR tyrosine kinase inhibitors effectively suppressed the migration and tube formation of vascular endothelial cells. Furthermore, activating transcription factor 6 (ATF6) induced the upregulation of EGF, and its antagonism effectively suppressed these SCC-mediated events and inhibited tumor recurrence after chemotherapy. These results suggest that the ATF6-EGF signaling axis in SCCs functions to trigger the angiogenesis switch in residual tumors after chemotherapy and is thus a driving force for the switch from SCCs to actively cycling cancer cells, leading to tumor recurrence.

Egr-1 gene is induced by the systemic administration of the vascular endothelial growth factor and the epidermal growth factor

Blood ◽  
2000 ◽  
Vol 96 (5) ◽  
pp. 1772-1781
Author(s):  
Lixin Liu ◽  
Jo C. Tsai ◽  
William C. Aird
Keyword(s):  
Skeletal Muscle ◽  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Mrna Levels ◽  
Vascular Endothelial ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

Egr-1 is a transcription factor that couples short-term changes in the extracellular milieu to long-term changes in gene expression. In cultured endothelial cells, the Egr-1 gene has been shown to respond to a variety of extracellular signals. However, the physiological relevance of these findings remains unclear. To address this question, the growth factor-mediated response of the Egr-1 gene under in vivo conditions was analyzed. To that end, either vascular endothelial growth factor (VEGF) or epidermal growth factor (EGF) was injected into the intraperitoneal cavity of mice. Growth factors were delivered to all tissues examined, as evidenced by the widespread distribution of I125-labeled growth factors and the phosphorylation of their respective receptors. In Western blot analyses of whole-tissue extracts, Egr-1 protein levels were shown to be induced in the heart, brain, liver, and spleen of VEGF-treated mice, and in the heart, lung, brain, liver and skeletal muscle of EGF-treated animals. Changes in Egr-1 levels did not correlate with changes in receptor phosphorylation or ERK1/2 phosphorylation. In Northern blot analyses, VEGF induced Egr-1 mRNA levels in all tissues examined except lung and kidney, whereas EGF led to increased transcripts in all tissues except kidney. In immunofluorescence studies, VEGF induced Egr-1 in microvascular endothelial cells of the heart and liver, and EGF induced Egr-1 in the microvascular bed of skeletal muscle. Taken together, these results suggest that the Egr-1 gene is differentially regulated in response to systemically administered VEGF and EGF.

Egr-1 gene is induced by the systemic administration of the vascular endothelial growth factor and the epidermal growth factor

Blood ◽  
2000 ◽  
Vol 96 (5) ◽  
pp. 1772-1781 ◽  
Author(s):  
Lixin Liu ◽  
Jo C. Tsai ◽  
William C. Aird
Keyword(s):  
Skeletal Muscle ◽  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Mrna Levels ◽  
Vascular Endothelial ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

Abstract Egr-1 is a transcription factor that couples short-term changes in the extracellular milieu to long-term changes in gene expression. In cultured endothelial cells, the Egr-1 gene has been shown to respond to a variety of extracellular signals. However, the physiological relevance of these findings remains unclear. To address this question, the growth factor-mediated response of the Egr-1 gene under in vivo conditions was analyzed. To that end, either vascular endothelial growth factor (VEGF) or epidermal growth factor (EGF) was injected into the intraperitoneal cavity of mice. Growth factors were delivered to all tissues examined, as evidenced by the widespread distribution of I125-labeled growth factors and the phosphorylation of their respective receptors. In Western blot analyses of whole-tissue extracts, Egr-1 protein levels were shown to be induced in the heart, brain, liver, and spleen of VEGF-treated mice, and in the heart, lung, brain, liver and skeletal muscle of EGF-treated animals. Changes in Egr-1 levels did not correlate with changes in receptor phosphorylation or ERK1/2 phosphorylation. In Northern blot analyses, VEGF induced Egr-1 mRNA levels in all tissues examined except lung and kidney, whereas EGF led to increased transcripts in all tissues except kidney. In immunofluorescence studies, VEGF induced Egr-1 in microvascular endothelial cells of the heart and liver, and EGF induced Egr-1 in the microvascular bed of skeletal muscle. Taken together, these results suggest that the Egr-1 gene is differentially regulated in response to systemically administered VEGF and EGF.

scholarly journals Primary human endothelial cells secrete agents that reduce responsiveness to lysophosphatidic acid (LPA)

2012 ◽  
Vol 32 (4) ◽  
pp. 393-400 ◽  
Author(s):  
Eun Young Park ◽  
Andrius Kazlauskas
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Lysophosphatidic Acid ◽  
Umbilical Vein ◽  
Vascular Endothelial ◽  
Human Endothelial Cells ◽  
Lpa Receptor ◽  
And Migration ◽  
Endothelial Growth Factor ◽  
Proliferation And Migration

The plasma level of LPA (lysophosphatidic acid) (200–600 nM) is well within the range that promotes proliferation and migration of vascular ECs (endothelial cells), yet vessels are quiescent and stable. In this report, we considered one explanation for this paradox: that ECs secrete agents that attenuate responsiveness to LPA. Indeed, we observed that CM (conditioned medium) from confluent, quiescent cultures of primary HUVECs (human umbilical vein ECs) contained an agent that inhibited LPA-mediated signalling events and cellular responses. The putative inhibitor, which we tentatively call ILMR (inhibitor of LPA-mediated responsiveness) seemed to act on cells (instead of at the level of LPA) by suppressing the ability of LPA receptor 1 to signal. The amount and/or activity of ILMR was regulated by growth factors; exposing HUVECs to VEGF-A (vascular endothelial growth factor A), but not bFGF (basic fibroblast growth factor), reduced the amount and/or activity of ILMR in CM. We conclude that in addition to promoting angiogenesis directly, VEGF-A can also act indirectly by modulating the bioactivity of angiomodulators such as LPA.

A monokine regulates colony-stimulating activity production by vascular endothelial cells

Blood ◽  
1983 ◽  
Vol 62 (3) ◽  
pp. 663-668 ◽  
Author(s):  
GC Jr Bagby ◽  
E McCall ◽  
KA Bergstrom ◽  
D Burger
Keyword(s):  
Endothelial Cells ◽  
Bone Marrow Cells ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Cell Types ◽  
Colony Growth ◽  
Mononuclear Phagocytes ◽  
Vascular Endothelial ◽  
Blood Monocytes ◽  
Colony Stimulating Activity

Abstract Human umbilical vein endothelial cells were cultured in supernatants of peripheral blood monocytes that had been cultured for 3 days with and without lactoferrin. Colony-stimulating activity (CSA) was measured in supernatants of the endothelial cell cultures and appropriate control cultures using normal, T-lymphocyte-depleted, phagocyte-depleted, low- density bone marrow cells in colony growth (CFU-GM) assays. Monocyte- conditioned medium contained a nondialyzable, heat labile factor that enhanced 4–15--fold the production of CSA by endothelial cells. The addition of lactoferrin to monocyte cultures reduced the activity of this monokine by 69%. Lactoferrin did not inhibit CSA production by monokine-stimulated endothelial cells. Therefore, vascular endothelial cells are potent sources of CSA, the production of CSA by these cells is regulated by a stimulatory monokine, and the production and/or release of the monokine is inhibited by lactoferrin, a neutrophil- derived putative feedback inhibitor of granulopoiesis. Inasmuch as a similar monokine is known to stimulate CSA production by fibroblasts and T lymphocytes, we suggest that mononuclear phagocytes play a pivotal role in the regulation of granulopoiesis by recruiting a variety of cell types to produce CSA.

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