FGFR-1 regulates angiogenesis through cytokines interleukin-4 and pleiotrophin

The role of fibroblast growth factors (FGFs) in blood vessel formation has remained unclear. We used differentiating stem-cell cultures (embryoid bodies) and teratomas to show that FGF receptor-1 (FGFR-1) exerts a negative regulatory effect on endothelial cell function in these models. Embryoid bodies lacking expression of FGFR-1 as a result of gene targeting (Fgfr-1−/−) displayed increased vascularization and a distinct, elongated vessel morphology. Teratomas derived from FGFR-1–deficient stem cells were characterized by an increased growth rate and abundant, morphologically distinct vessels. Transmission electron microscopy of the Fgfr-1−/− teratomas showed a compact and voluminous but functional endothelium, which anastomosed with the host circulation. The increased vascularization and altered endothelial cell morphology was dependent on secreted factor(s), based on the transfer of the Fgfr-1−/− vascular phenotype by conditioned medium to Fgfr-1+/− embryoid bodies. Antibody and transcript arrays showed down-regulation of interleukin-4 (IL-4) and up-regulation of pleiotrophin in Fgfr-1−/− embryoid bodies, compared with the heterozygous cultures. We used neutralizing antibodies to show that IL-4 and pleiotrophin act as negative and positive angiogenic regulators, respectively. We conclude that FGFR-1 negatively regulates endothelial cell function by altering the balance of modulatory cytokines.

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Endothelial Cell Function, Including Tissue Factor Expression, Under Flow Conditions

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642664 ◽

1995 ◽

Vol 74 (01) ◽

pp. 123-128 ◽

Cited By ~ 40

Author(s):

Eric F Grabowski ◽

Frances P Lam

Keyword(s):

Endothelial Cell ◽

Tissue Factor ◽

Cell Function ◽

Tissue Factor Expression ◽

Flow Conditions ◽

Endothelial Cell Function ◽

Factor Expression

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Do DPP-4 inhibitors improve endothelial cell function?

10.35841/cardiology.1.1.12-14 ◽

2017 ◽

Vol 01 (01) ◽

Author(s):

Hiroshi Nomoto ◽

Hideaki Miyoshi ◽

Akinobu Nakamura ◽

Tatsuya Atsumi ◽

Naoki Manda ◽

...

Keyword(s):

Endothelial Cell ◽

Cell Function ◽

Endothelial Cell Function

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Estrogen Restores Endothelial Cell Function in an Experimental Model of Vascular Injury

Circulation ◽

10.1161/01.cir.96.5.1624 ◽

1997 ◽

Vol 96 (5) ◽

pp. 1624-1630 ◽

Cited By ~ 60

Author(s):

C. Roger White ◽

Jonathan Shelton ◽

Shi-Juan Chen ◽

Victor Darley-Usmar ◽

Leslie Allen ◽

...

Keyword(s):

Endothelial Cell ◽

Experimental Model ◽

Vascular Injury ◽

Cell Function ◽

Endothelial Cell Function

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Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia

Journal of Endocrinology ◽

10.1530/joe-16-0340 ◽

2017 ◽

Vol 232 (1) ◽

pp. R27-R44 ◽

Cited By ~ 90

Author(s):

D S Boeldt ◽

I M Bird

Keyword(s):

Endothelial Cell ◽

Endothelial Dysfunction ◽

Cell Function ◽

Endothelial Cell Dysfunction ◽

Hypertensive Disorders Of Pregnancy ◽

Endothelial Cell Function ◽

Vascular Adaptation ◽

Cell Dysfunction ◽

Maternal Adaptation ◽

Flow Through

Maternal vascular adaptation to pregnancy is critically important to expand the capacity for blood flow through the uteroplacental unit to meet the needs of the developing fetus. Failure of the maternal vasculature to properly adapt can result in hypertensive disorders of pregnancy such as preeclampsia (PE). Herein, we review the endocrinology of maternal adaptation to pregnancy and contrast this with that of PE. Our focus is specifically on those hormones that directly influence endothelial cell function and dysfunction, as endothelial cell dysfunction is a hallmark of PE. A variety of growth factors and cytokines are present in normal vascular adaptation to pregnancy. However, they have also been shown to be circulating at abnormal levels in PE pregnancies. Many of these factors promote endothelial dysfunction when present at abnormal levels by acutely inhibiting key Ca2+ signaling events and chronically promoting the breakdown of endothelial cell–cell contacts. Increasingly, our understanding of how the contributions of the placenta, immune cells, and the endothelium itself promote the endocrine milieu of PE is becoming clearer. We then describe in detail how the complex endocrine environment of PE affects endothelial cell function, why this has contributed to the difficulty in fully understanding and treating this disorder, and how a focus on signaling convergence points of many hormones may be a more successful treatment strategy.

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Shear stress regulates endothelial cell function through SRB1-eNOS signaling pathway

Cardiovascular Therapeutics ◽

10.1111/1755-5922.12199 ◽

2016 ◽

Vol 34 (5) ◽

pp. 308-313 ◽

Cited By ~ 8

Author(s):

Ying Zhang ◽

Bin Liao ◽

Miaoling Li ◽

Min Cheng ◽

Yong Fu ◽

...

Keyword(s):

Shear Stress ◽

Endothelial Cell ◽

Signaling Pathway ◽

Cell Function ◽

Endothelial Cell Function

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Hypothermic machine perfusion of rat livers preserves endothelial cell function

Transplantation Proceedings ◽

10.1016/j.transproceed.2004.11.075 ◽

2005 ◽

Vol 37 (1) ◽

pp. 335-337 ◽

Cited By ~ 6

Author(s):

H. Xu ◽

J.X. Zhang ◽

J.W. Jones ◽

J.H. Southard ◽

M.G. Clemens ◽

...

Keyword(s):

Endothelial Cell ◽

Cell Function ◽

Machine Perfusion ◽

Endothelial Cell Function ◽

Hypothermic Machine Perfusion ◽

Rat Livers

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Abstract 203: Glucose Stimulated Endothelial Microparticles Increase Endothelial Cell Apoptotic Susceptibility

Circulation Research ◽

10.1161/res.121.suppl_1.203 ◽

2017 ◽

Vol 121 (suppl_1) ◽

Author(s):

Tyler Bammert ◽

Jamie Hijmans ◽

Whitney Reiakvam ◽

Ma’ayan Levy ◽

Kelly Stockelman ◽

...

Keyword(s):

Endothelial Cell ◽

Caspase 3 ◽

Cell Function ◽

Culture Media ◽

Umbilical Vein ◽

Endothelial Cell Function ◽

Cellular Expression ◽

Apoptotic Effect ◽

Clinical Interest ◽

Umbilical Vein Endothelial Cells

Clinical interest in endothelial cell-derived microparticles (EMPs) has increased due to their role in the pathogenesis of vascular disease. Although released by the endothelium, EMPs have autocrine properties that can significantly impact endovascular health. Hyperglycemic conditions, such as diabetes, are known to stimulate EMP release; however, the effects of these glucose-related microparticles on endothelial cell function are not well understood. High glucose concentrations induce endothelial cell apoptosis through a caspase-3-dependent mechanism. The aim of this study was to determine the effect of EMPs derived from a hyperglycemic condition on endothelial cell susceptibility to apoptosis. Human umbilical vein endothelial cells (HUVECs) were cultured (3 rd passage) and plated in 6-well plates at a density of 5.0 x 10 5 cell/condition. Cells were incubated with RPMI 1640 media containing 25mM D-glucose (concentration representing a diabetic glycemic state) or 5mM D-glucose (control, normoglycemic, condition) for 48 h to generate EMPs. EMPs derived from both conditions were pelleted by centrifugation and resuspended in culture media. EMP identification (CD144 + expression) and number was determined by flow cytometry. HUVECs (2 x10 6 cells/condition) were treated with EMPs (2:1 ratio) generated from either the hyperglycemic or normoglycemic conditions for 24 h. Thereafter, cells were treated with staurosporine (1μmol/L) for 3 h at 37°C and biotin-ZVKD-fmk inhibitor for 1 h at 37°C. Intracellular concentration of active caspase-3 was determined by enzyme immune assay. Cellular expression of miR-Let7a, an anti-apoptotic microRNA, was determined by RT-PCR using the ΔΔCT normalized to RNU6. Hyperglycemic EMPs resulted in significant increase in basal (1.5 + 0.1 vs 1.0 + 0.1 ng/mL) and staurosporine-stimulated (2.2 + 0.2 vs 1.4 + 0.1 ng/mL) caspase-3 activity compared with normoglycemic EMPs. Additional, the expression of miR-Let7a was markedly reduced (~140%) in response to hyperglycemic EMPs (0.43 + 0.17 fold vs control). These results demonstrate that hyperglycemic-induced EMPs increase endothelial cell apoptotic susceptibility. This apoptotic effect may be mediated, at least in part, by a reduction in miR-Let7a expression.

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Enhanced Vascular Endothelial Cell Function on Nanostructured Titanium Surface Features: The Role of Nano to Submicron Roughness

MRS Proceedings ◽

10.1557/proc-1136-dd04-04 ◽

2008 ◽

Vol 1136 ◽

Cited By ~ 2

Author(s):

Jing Lu ◽

Dongwoo Khang ◽

Thomas J. Webster

Keyword(s):

Cell Adhesion ◽

Endothelial Cell ◽

Cell Function ◽

Vascular Endothelial Cell ◽

Vascular Endothelial ◽

Endothelial Cell Function ◽

Titanium Surfaces ◽

Endothelial Cell Adhesion

ABSTRACTTo study the contribution of different surface feature properties in improving vascular endothelial cell adhesion, rationally designed nano/sub-micron patterns with various dimensions were created on titanium surfaces in this study. In vitro results indicated that endothelial cell adhesion was improved when the titanium pattern dimensions decreased into the nano-scale. Specifically, endothelial cells preferred to adhere on sub-micron and nano rough titanium substrates compared to flat titanium. Moreover, titanium with nano and sub-micron roughness and with the same chemistry as compared to flat titanium, had significantly greater surface energy. Thus, the present study indicated the strong potential of surface nanotopography and nano/sub-micron roughness for improving current vascular stent design.

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