<i>In Vitro</i> and <i>In Vivo</i> Effects of Human Monocytes and their Subsets on New Vessel Formation

Czepluch, Frauke S.; Bernhardt, Markus; Kuschicke, Hendrik; Gogiraju, Rajinikanth; Schroeter, Marco R.; Riggert, Joachim; Hasenfuß, Gerd; Schäfer, Katrin

doi:10.1111/micc.12100

Cited by 7 publications

(9 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mo are a heterogeneous cell population and it has been reported that Mo subsets possess distinct cell surface markers and functional characteristics relevant to their contribution to angiogenesis . The identification of different angiogenic properties of Mo prompted several investigators to perform studies to delineate the functional significance of each subset.…”

Section: Discussionmentioning

confidence: 99%

Tissue factor variants induce monocyte transformation and transdifferentiation into endothelial cell‐like cells

Arderiu

Espinosa

Peña

et al. 2017

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

Background Monocytes (Mo) increase neovascularization by releasing proangiogenic mediators and/or transdifferentiating into endothelial cell-like (ECL) cells. Recently, we have reported that Mo-microvascular endothelial cells (mECs) crosstalk induces mEC-tissue factor (TF) expression and promotes angiogenesis. However, the effect of TF on Mo remains unknown. Objective Here, we analyzed whether TF might exert angiogenic effects by inducing transdifferentiation of Mo. Methods Full-length TF (flTF) and alternatively spliced TF (asTF) were overexpressed in mECs, and their supernatants were added to Mo cultures. CD16 positivity and expression of vascular endothelial cell (VEC) markers in Mo were analyzed by fluorescence activated cell sorting. The capacity to form tube-like structures were visualized in three-dimensional cultures. Results In mECs flTF and asTF expression and release were increased in cultures with Mo-conditioned media. TF variants induced expansion of a CD16 Mo subset and Mo transdifferentiation into ECL-cells expressing VEC markers that can form new microvessels. CD16 Mo exposed to TF showed an increased expression of VE-cadherin, von Willebrand factor (VWF) and eNOS. Mo cultured with supernatants obtained from TF-silenced mECs did not transdifferentiate to ECL-cells or expressed VEC markers. Blocking β1-integrin in Mo significantly blocked the effects of the TF variants. Conclusions Mo induce mECs to express and release TF, which drives CD16 Mo to transform into CD16 Mo and to transdifferentiate into ECL-cells that can form new microvessels. Our results reveal a TF-mediated positive feedback between mECs and Mo that stimulates Mo differentiation and induces angiogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Tissue factor variants induce monocyte transformation and transdifferentiation into endothelial cell‐like cells

Arderiu

Espinosa

Peña

et al. 2017

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

show abstract

“…Infiltration of inflammatory cells in hypoxic areas is a hallmark to tissue ischemia (Silvestre et al, 2008). Monocytes have been shown to promote angiogenesis by releasing angiogenic growth factors, cytokines, and metalloproteinases (Czepluch et al, 2014;Jaipersad et al, 2014). Interaction between monocytes and ECs results in crossmodulation of several biological functions.…”

Section: Introductionmentioning

confidence: 99%

Monocyte-secreted Wnt5a interacts with FZD5 in microvascular endothelial cells and induces angiogenesis through tissue factor signaling

Arderiu

Espinosa

Peña

et al. 2014

Journal of Molecular Cell Biology

View full text Add to dashboard Cite

Angiogenesis during reactive and pathologic processes is characteristically associated with inflammation. Inflammatory cells participate in angiogenesis by secreting different molecules that affect endothelial cell functions. We had previously shown that induced tissue factor (TF) expression in activated microvascular endothelial cells (mEC) is able to induce angiogenesis via autocrine regulation. However, the signals that induce TF expression in mEC are not fully known. Here, we demonstrate that monocyte paracrine cross-talk with mECs triggers mEC-TF expression. We have identified that monocyte-secreted Wnt5a induces TF expression in mEC and functionally induces cell monolayer repair and angiotube formation in vitro as well as microvessel formation in vivo. Monocyte-secreted Wnt5a activates FZD5 in mECs, which signals to induce the release of intracellular Ca(2+) and increase NFκB transcription activity and TF gene expression. In sum, Wnt5a secreted by monocytes signals through the noncanonical Wnt-FZD5 pathway in mECs to induce TF expression that induces angiogenesis by autocrine regulation.

show abstract

“…These cells perform various functions after MI, including removing damaged extracellular matrix and dying cardiac cells, releasing inflammatory mediators, and promote angiogenesis by releasing growth factors, cytokines and metalloproteinases [103,104]. Interestingly, macrophages have been observed to be able to carve out tunnels in the extracellular matrix mediating angiogenesis [105].…”

Section: The Role Of Apelin In Monocytes/macrophagesmentioning

confidence: 97%

Apelinergic system in endothelial cells and its role in angiogenesis in myocardial ischemia

Nováková

Sandhu

Dragomir-Daescu

et al. 2016

Vascular Pharmacology

View full text Add to dashboard Cite

In Vitro and In Vivo Effects of Human Monocytes and their Subsets on New Vessel Formation

Abstract: Our findings suggest additive and differential effects of monocyte subsets during neovascularization processes, possibly due to an altered secretion of angiogenic factors and their paracrine capacity to stimulate new vessel formation.

Cited by 7 publications

References 35 publications

Tissue factor variants induce monocyte transformation and transdifferentiation into endothelial cell‐like cells

Tissue factor variants induce monocyte transformation and transdifferentiation into endothelial cell‐like cells

Monocyte-secreted Wnt5a interacts with FZD5 in microvascular endothelial cells and induces angiogenesis through tissue factor signaling

Apelinergic system in endothelial cells and its role in angiogenesis in myocardial ischemia

Contact Info

Product

Resources

About