scholarly journals Role of vitamin D in cell-cell interaction of fetal endothelial progenitor cells and umbilical cord endothelial cells in a preeclampsia-like model

2019 ◽  
Vol 317 (2) ◽  
pp. C348-C357 ◽  
Author(s):  
L. Brodowski ◽  
B. Schröder-Heurich ◽  
C. A. Hubel ◽  
T. H. Vu ◽  
C. S. von Kaisenberg ◽  
...  
Keyword(s):  
Vitamin D ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Endothelial Progenitor ◽  
Cord Serum ◽  
Mediated Effects ◽  
Fetal Serum

Maternal endothelial dysfunction is a cental feature of preeclampsia (PE), a hypertensive disorder of pregnancy. Factors in the maternal circulation are thought to contribute to this endothelial dysfunction. Although understudied, factors in the fetal circulation may influence fetal endothelial cell interactions with endothelial progenitor cells as critical steps in placental angiogenesis. We hypothesize that cell-cell interactions that are important for pregnancy health are impaired by fetal serum from PE pregnancies and that 1,25(OH)2-vitamin D3 attenuates the negative effects of this serum on cell function. We tested the ability of fetal cord blood-derived endothelial progenitor cells [endothelial colony-forming cells (ECFCs)] to invade into established monolayers and capillary tubule-like structures of human fetal umbilical venous endothelial cells (HUVECs), while in the presence/absence of fetal cord serum from uncomplicated or PE pregnancies, and tested the ability of 1,25(OH)2-vitamin D3 to modulate the serum-mediated effects. PE cord serum reduced the invasion of fetal ECFCs into HUVEC monolayers or tubule networks. Vitamin D attenuated these effects of PE fetal serum on endothelial functional properties. Immunocytochemical studies revealed involvement of VE-cadherin contacts in interactions between ECFCs and mature fetal endothelial cells. PE cord serum reduces the ability of fetal endothelial progenitor cells to incorporate into fetal endothelial cell networks. Physiologic concentrations of vitamin D reverse these PE serum-mediated effects. These data appear consistent with lines of evidence that vitamin D has antipreeclampsia effects.

Abstract 894: Leptin Potentiates the Angiogenic Properties of Endothelial Progenitor Cells In Vitro and In Vivo

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Nana-Maria Heida ◽  
Marco R Schroeter ◽  
I-Fen Cheng ◽  
Elena I Deryugina ◽  
Thomas Korff ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Tube Length ◽  
Endothelial Progenitor ◽  
Signal Transduction Inhibitors ◽  
Stimulation Of

Endothelial progenitor cells (EPC) have been reported to contribute to neovascularization. We have previously shown that the adipocytokine leptin may enhance the adhesive properties of EPC by upregulating specific integrins. To investigate whether the angiogenic effects of leptin may be mediated by modulation of EPC function, mononuclear cells were isolated from healthy human volunteers and cultivated under endothelial cell conditions for 7 days. In the matrigel assay, pretreatment of EPC with recombinant leptin for 24 hours dose-dependently enhanced their incorporation into tubular structures provided by mature endothelial cells. For example, 138.3 ± 7.6% (P = 0.001) and 145.3 ± 5.5% (P = 0.0001) CM-DiI-labeled EPC were detected after stimulation with 10 and 100 ng/mL leptin, respectively (control-treated EPC defined as 100%). Furthermore, in the spheroid angiogenesis assay, stimulation of EPC with 10 ng/mL leptin increased the number of sprouts (P < 0.0001) and tube length (P < 0.0001) of coincubated mature endothelial cells, and the outgrowth of EPC (P < 0.0001). Addition of 100-fold excess of leptin-neutralizing or leptin-receptor-binding antibodies completely reversed these effects. Moreover, EPC adhesion onto endothelial cell tubules could be reduced by addition of RGD peptides (from 159 ± 13.7% to 101.8 ± 14.6%; P = 0.02), or of neutralizing antibodies against αvβ3 (from 165.3 ± 11.8% to 103.8 ± 13.3%; P = 0.006) or αvβ5 (to 93.5 ± 15.8%; P = 0.005). Further experiments using specific signal transduction inhibitors (10 μM of LY294002, PD98059, or SB203580), as well as Western blot analysis, revealed that leptin signaling in EPC involves phosphoinositide-3 kinase and p42/44, but not by p38 MAP kinase. The effects of leptin could also be confirmed under in vivo conditions. Stimulation of EPC with 100 ng/mL leptin potentiated the insprout of newly formed avian vessels into collagen onplants placed on the chorion allantoic membrane of chicken embryos (angiogenic index, 0.58 ± 0.24) compared to control-treated EPC (0.44 ± 0.27; P = 0.07) and endothelial basal medium alone (0.31 ± 0.26; P = 0.0007). Thus, our in vitro and in vivo results suggest that the angiogenic effects of leptin may partly depend on its specific interaction with endothelial progenitor cells.

Fluid shear stress induces arterial differentiation of endothelial progenitor cells

2009 ◽  
Vol 106 (1) ◽  
pp. 203-211 ◽  
Author(s):  
Syotaro Obi ◽  
Kimiko Yamamoto ◽  
Nobutaka Shimizu ◽  
Shinichiro Kumagaya ◽  
Tomomi Masumura ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Peripheral Blood ◽  
Consensus Sequence ◽  
Mrna Levels ◽  
Endothelial Progenitor ◽  
Cell Markers

Endothelial progenitor cells (EPCs) are mobilized from bone marrow to peripheral blood and contribute to angiogenesis in tissues. In the process, EPCs are exposed to the shear stress generated by blood flow and tissue fluid flow. Our previous study showed that shear stress promotes differentiation of EPCs into mature endothelial cells. In this study, we investigated whether EPCs differentiate into arterial or venous endothelial cells in response to shear stress. When cultured EPCs derived from human peripheral blood were exposed to controlled levels of shear stress in a flow-loading device, the mRNA levels of the arterial endothelial cell markers ephrinB2, Notch1/3, Hey1/2, and activin receptor-like kinase 1 increased, but the mRNA levels of the venous endothelial cell markers EphB4 and neuropilin-2 decreased. Both the ephrinB2 increase and the EphB4 decrease were shear stress dependent rather than shear rate dependent. EphrinB2 protein was increased in shear-stressed EPCs, and the increase in ephrinB2 expression was due to activated transcription and not mRNA stabilization. Deletion analysis of the ephrinB2 promoter indicated that the cis-element (shear stress response element) is present within 106 bp 5′ upstream from the transcription initiation site. This region contains the Sp1 consensus sequence, and a mutation in its sequence decreased the basal level of transcription and abolished shear stress-induced ephrinB2 transcription. Electrophoretic mobility shift assays and chromatin immunoprecipitation assays showed that shear stress markedly increased binding of Sp1 to its consensus sequence. These results indicate that shear stress induces differentiation of EPCs into arterial endothelial cells by increasing ephrinB2 expression in EPCs through Sp1 activation.

Abstract 3668: Endothelial Progenitor Cells Express Connexins which may be Important for the Functional Integration of Circulating Progenitor Cells into the Endothelium

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Vasileios Petoumenos ◽  
Georg Nickenig ◽  
Nikos Werner
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Mononuclear Cells ◽  
Functional Integration ◽  
Dye Transfer ◽  
Human Coronary Artery ◽  
Endothelial Progenitor ◽  
Calcein Am

Bone marrow (BM)-derived endothelial progenitor cells (EPC) enhance endothelial cell (EC) repair after focal EC damage, improve endothelial dysfunction, and are an important cellular risk predictor for cardiovascular mortality. For an effective EC repair, functional integration of circulating EPC into the damaged endothelium is a pre-requisite. Here, we determine the importance of connexins (Cx) for the interaction with mature ECs. Expression of Cx was evaluated on magnetic-bead selected CD133+ cells using immunocytochemistry and flow cytometry. CD133+ cells expressed Cx 40 and Cx 43 but not Cx 37. Mononuclear cells were cultivated to obtain early outgrowth EPC or colony forming units-endothelial cells (CFU-EC). Cx 37, 40, and 43 were expressed on cultured EPC. Co-culture experiments with mature human coronary artery endothelial cells (HCAEC) and EPC demonstrated the development of Cx 40, and 43 positive gap-junctions between both cells types. In order to investigate whether the interaction between HCAEC and EPC results in a functional communication between cells, dye transfer experiments were performed. Di-Ac-LDL labelled EPC transformed into Di-Ac-LDL and Calcein AM double positive cells when co-cultured with Calcein AM positive HCAEC and vice versa. In order to study the role of connexins in reendothelialization, C57bl6 (wild-type, WT) mice were subjected to a focal endothelial cell denudation and repetitively treated with WT and Cx37−/− deficient mononuclear cells. In contrast to the treatment with WT mononuclear cells, treatment with Cx37−/− cells was not associated with enhanced reendothelialization. Furthermore, endothelial function of isolated aortic rings derived from Cx37−/− mice showed an impaired endothelial-dependent vasorelaxation compared to WT mice. We provide evidence that connexins are differentially expressed on immature naíve EPC and cultured early-outgrowth EPC. The expression of connexin 37, 40, and 43 may be required for the functional integration of endothelial progenitor cells into the damaged endothelium.

Presence of endothelial progenitor cells, distinct from mature endothelial cells, within human CD146+ blood cells

2005 ◽  
Vol 94 (12) ◽  
pp. 1270-1279 ◽  
Author(s):  
Bruno Delorme ◽  
Agnès Basire ◽  
Carla Gentile ◽  
Florence Sabatier ◽  
Frédéric Monsonis ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Network Formation ◽  
Mononuclear Cells ◽  
Circulating Endothelial Cells ◽  
Endothelial Progenitor ◽  
Color Flow ◽  
Immunodeficient Mice ◽  
Circulating Cells

SummaryCD146 is an adhesion molecule present on endothelial cells throughout the vascular tree. CD146 is also expressed by circulating endothelial cells (CECs) widely considered to be mature endothelial cells detached from injured vessels. The discovery of circulating endothelial progenitor cells (EPCs) originating from bone marrow prompted us to investigate whether CD146 circulating cells could also contains EPCs. We tested this hypothesis using an approach combining elimination of CECs by an adhesion step, followed by immunomagnetic sorting of remaining CD146+ cells from the non adherent fraction of cord blood mononuclear cells. When cultured under endothelial-promoting conditions, these cells differentiated as late outgrowth endothelial colonies: they grew as a cobblestone monolayer, were uniformly positive for endothelial markers and did not express leukocyte antigens. They highly proliferated and were expanded in long-term culture without alterations of their phenotypic and functional properties (DiI-ac-LDL uptake, wound repair, capillary-like network formation, and TNFα response). Moreover, these cells colonized a Matrigel plug in immunodeficient mice (NOD/SCID). Finally, using 4-color flow cytometry analysis of purified CD34+ cells, we clearly discriminated, CD146+ EPCs (CD146+ CD34+ CD45+ CD133+ or CD117+), and CD146+ CECs (CD146+ CD34+, CD45− CD133− or CD117−), both in cord and adult peripheral blood. The relative proportions of the two CD146+ subsets varied in patients with myocardial infarction as compared to healthy subjects. Our study establishes that, beside CECs, CD146+ circulating cells contain a subpopulation of EPCs with potential use in proangiogenic therapy. In addition, the dual measurement of CD146+ CECs and CD146+ EPCs offers a promising tool for monitoring vascular injury/regeneration processes in clinical situations.

scholarly journals Immune privilege of endothelial cells differentiated from endothelial progenitor cells

2010 ◽  
Vol 88 (1) ◽  
pp. 121-129 ◽  
Author(s):  
Juliane Ladhoff ◽  
Bernhard Fleischer ◽  
Yoshiaki Hara ◽  
Hans-Dieter Volk ◽  
Martina Seifert
Keyword(s):  
Endothelial Cells ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Immune Privilege ◽  
Endothelial Progenitor
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