scholarly journals Vasculogenesis and angiogenesis in modular collagen–fibrin microtissues

2014 ◽  
Vol 2 (10) ◽  
pp. 1497-1508 ◽  
Author(s):  
A. W. Peterson ◽  
D. J. Caldwell ◽  
A. Y. Rioja ◽  
R. R. Rao ◽  
A. J. Putnam ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Vessel ◽  
Tissue Development ◽  
Blood Vessel Formation ◽  
Vessel Formation ◽  
Surrounding Matrix ◽  
Vasculogenesis And Angiogenesis ◽  
Vessel Networks

Vessel networks can be generated within modular protein microbeads containing endothelial cells and fibroblasts. Embedding these microtissues in a surrounding matrix emulates aspects of new blood vessel formation, a process that is critical in tissue development, remodeling, and regeneration.

scholarly journals Emerging Role of AP-1 Transcription Factor JunB in Angiogenesis and Vascular Development

2021 ◽  
Vol 22 (6) ◽  
pp. 2804
Author(s):  
Yasuo Yoshitomi ◽  
Takayuki Ikeda ◽  
Hidehito Saito-Takatsuji ◽  
Hideto Yonekura
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Blood Vessel ◽  
Vascular Endothelial Cells ◽  
Vascular Development ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial ◽  
Blood Vessel Formation ◽  
Vessel Formation

Blood vessels are essential for the formation and maintenance of almost all functional tissues. They play fundamental roles in the supply of oxygen and nutrition, as well as development and morphogenesis. Vascular endothelial cells are the main factor in blood vessel formation. Recently, research findings showed heterogeneity in vascular endothelial cells in different tissue/organs. Endothelial cells alter their gene expressions depending on their cell fate or angiogenic states of vascular development in normal and pathological processes. Studies on gene regulation in endothelial cells demonstrated that the activator protein 1 (AP-1) transcription factors are implicated in angiogenesis and vascular development. In particular, it has been revealed that JunB (a member of the AP-1 transcription factor family) is transiently induced in endothelial cells at the angiogenic frontier and controls them on tip cells specification during vascular development. Moreover, JunB plays a role in tissue-specific vascular maturation processes during neurovascular interaction in mouse embryonic skin and retina vasculatures. Thus, JunB appears to be a new angiogenic factor that induces endothelial cell migration and sprouting particularly in neurovascular interaction during vascular development. In this review, we discuss the recently identified role of JunB in endothelial cells and blood vessel formation.

scholarly journals Contribution of Endothelial Cells of Hematopoietic Origin to Blood Vessel Formation

2001 ◽  
Vol 88 (1) ◽  
Author(s):  
Eberhard Gunsilius ◽  
Hans-Christoph Duba ◽  
Andreas L. Petzer ◽  
Christian M. Kähler ◽  
Günther A. Gastl
Keyword(s):  
Endothelial Cells ◽  
Blood Vessel ◽  
Blood Vessel Formation ◽  
Vessel Formation

Multi-Lineage Potential of Human Monocyte-Derived Mesenchymal Progenitors (MOMPs).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3595-3595
Author(s):  
Masataka Kuwana ◽  
Hiroaki Kodama ◽  
Yuka Okazaki ◽  
Takashi Satoh ◽  
Takafumi Inoue ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Transcription Factors ◽  
Blood Vessel ◽  
Carcinoma Cells ◽  
Type I ◽  
Differentiation Potential ◽  
Rat Cardiomyocytes ◽  
Blood Vessel Formation ◽  
Vessel Formation ◽  
Autologous Cell Transplantation

Abstract Circulating CD14+ monocytes are known to be precursors of phagocytes, such as macrophages and dendritic cells. We have recently identified a novel CD14+CD45+CD34+type I collagen+ cell fraction derived from human circulating CD14+ monocytes, monocyte-derived mesenchymal progenitor (MOMP), which contains progenitors capable of differentiating into a variety of mesenchymal cells, including bone, cartilage, fat and skeletal muscle (J Leukoc Biol2003;74:833). Here, we investigated a differentiation potential of human MOMPs along endothelial, cardiomyocytic, and neuronal lineages. MOMPs treated with angiogenic factors for 7 days underwent a change in their morphology from spindle-shaped to caudated. Transmission electron microscopic analysis revealed that these cells displayed rod-shaped microtubulated structures corresponding to Weibel-Palade bodies. Almost every cell expressed CD31, VE-vadherin, VEGFR2, Tie-2, von Willeband factor (vWF), eNOS and CD146, but CD14/CD45 expression was markedly down-regulated. Functional characteristics, including vWF release upon histamine stimulation, acetylated LDL uptake, and up-regulated expression of VEGFR1 in response to hypoxia, were indistinguishable between MOMP-derived endothelial-like cells and human umbilical vein endothelial cells. We further performed xenogenic transplantation studies using a SCID mouse model, in which syngeneic colon carcinoma cells were injected subcutaneously with or without human MOMPs. Tumors generated from carcinoma cells alone showed central necrosis and less blood vessel formation, but co-transplantation with MOMPs resulted in promotion of blood vessel formation and no areas of necrosis. Immunohistochemical analysis using human specific antibodies to CD31 and vWF demonstrated that >50% of blood vessels incorporated MOMP-derived endothelial cells. To investigate whether MOMPs were able to differentiate along cardiomyocytic and neuronal lineages, pre-labeled human MOMPs were co-cultivated with primary cultures of rat cardiomyocytes or neurons. Shortly after co-cultivation with rat cardiomyocytes, the majority of MOMPs expressed cardiomyocyte-specific transcription factors, Nkx2.5, GATA-4, eHAND and MEF2, together with CD14/CD45. Subsequently, a subpopulation of MOMPs expressed troponin I and atrial natriuretic peptide and lost CD14/CD45 expression. Spontaneously beating cells formed gap junctions with adjacent rat cardiomyocytes and exhibited electrophysiological properties of ventricular myocytes. MOMPs co-cultured with rat neurons for 3 days expressed neuron-specific transcription factors, Ngn-2, NeuroD, Mash1 and nestin. At day 7, these cells expressed neuron-specific markers, NeuN and Hu. At day 18, a subpopulation of the cells exhibited a neuron-like morphology, including characteristic axons and a refractile round cell body, and expressed MAP2 and β3-tubulin. Co-cultivation of MOMPs with rat cells induced to express GFP by adenoviral gene transfer resulted in appearance of human cardiomyoocytes and neurons without GFP staining, suggesting that our observations are not solely explained by cell fusion. In summary, human MOMPs are capable of differentiating along endothelial and cardiomyocytic lineages as well as a neuronal lineage of an ectoderm-origin. Circulating CD14+ monocytes can be an abundant and easily accessible source for autologous cell transplantation for tissue regeneration.

Abstract 182: Inhibitor of differentiation (Id)3 Regulation of the Vasculature in Adipose Tissue

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Victoria Osinski ◽  
Jennifer Kirby ◽  
Swapnil Sonkusare ◽  
Mete Civelek ◽  
Coleen McNamara
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Adipose Tissue ◽  
Blood Vessel ◽  
Vascular Development ◽  
Tissue Expansion ◽  
Dependent Manner ◽  
Blood Vessel Formation ◽  
Vessel Formation ◽  
Helix Loop Helix

Rationale: Over half of the U.S. is overweight or obese and excessive weight gain greatly increases one’s risk of cardiovascular disease. Adipose tissue requires new blood vessel formation to support transport of nutrients during expansion. Our lab has previously published that global loss of the helix-loop-helix transcription factor Inhibitor of differentiation 3 (Id3) results in attenuated increases in adipose depot size and microvascular blood volume in mice fed a high fat diet (HFD). Id3 has also been implicated in regulating tumor angiogenesis. Together, our results suggest that Id3 is regulating HFD-induced angiogenesis in adipose tissue. Methods and Results: To determine if Id3 is regulating angiogenesis, we performed genetic, cellular, and arterial experiments and analyses. Using bromodeoxyuridine (BrdU) treatments and flow cytometry, we found that endothelial cells within adipose tissue of mice with a global genetic knockout of Id3 (Id3 KO) had fewer proliferating (BrdU-positive) endothelial cells (0.0679% BrdU+CD31+ cells) than wild type (WT) mice (0.754% BrdU+CD31+). Using mouse adipose tissue gene expression data from the Gene Ontology Consortium database, we found that genes correlating most significantly with Id3 were functionally classified under categories of vascular development (p = 4.45E-8, correlation significance) and angiogenesis (p = 1.66E-6). Sox18, a known transcriptional regulator of blood vessel formation, shows higher relative gene expression in Id3 WT (1.42 ± 0.417) than Id3 KO (0.332 ± 0.126) adipose tissue. Finally, preliminary findings using pressure myography demonstrate that Id3 KO mice have a higher baseline arterial diameter than Id3 WT. Conclusion: Dysregulation of vascular development during adipose tissue expansion is altering arterial function in an Id3-dependent manner.

VEGF-VEGF Receptor 1 (Flt-1) Interactions Significantly Modulate Endothelial Progenitor Cell (EPC) Migration but Have Only Minor Effects on the Migration of Differentiated Endothelial Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3229-3229
Author(s):  
Bin Li ◽  
Amylynn A. Teleron ◽  
Charles Lin ◽  
Pampee P. Young
Keyword(s):  
Wound Healing ◽  
Endothelial Cells ◽  
Blood Vessel ◽  
Vegf Receptor ◽  
Blocking Antibody ◽  
Blood Vessel Formation ◽  
Migration Assay ◽  
Vessel Formation ◽  
Cellular Expression

Abstract There is a growing body of data demonstrating that vasculogenesis, whereby bone marrow -derived circulating progenitor cells (EPCs) home to sites of neovascularization, results in significant contribution to blood vessel formation during tumor growth, ischemic injury and wound healing. Vascular Endothelial Growth Factor (VEGF) has recently been shown to augment vasculogenesis. In the current study, we examined if VEGF/VEGF Receptor (VEGFR) interactions are important for EPC recruitment. Both VEGFR1 (flt-1) and VEGFR2 (flk-1) are strongly expressed, as detected by immunofluorescent and FACS analysis, on EPCs obtained by ex vivo expansion of human peripheral blood. In a modified Boyden chamber migration assay, EPCs showed dose dependent migration to VEGF. To examine receptor specificity, EPCs were preincubated with receptor blocking anti-VEGFR1 or -VEGFR2 prior to the migration assay. Level of inhibition by VEGFR1 blocking antibody was commensurate with blocking VEGFR2. Furthermore, migration in response to a VEGFR1-specific agonist, PlGF, was comparable to that induced by VEGF and was completely ablated by preincubation with VEGFR1 blocking antibody. By contrast, differentiated endothelial cells had diminished migration in response to PlGF as compared to VEGF. Furthermore, blocking VEGFR1 only mildly disrupted VEGF-induced migration of differentiated endothelial cells in vitro. Hence, unlike differentiated endothelial cells, EPC migration in vitro was mediated by both VEGF receptors. By quantitative RT-PCR, we examined the level of VEGFR1 and VEGFR2 mRNA transcripts in EPCs versus differentiated endothelial cells. VEGFR1 transcripts in EPCs were expressed 3-fold higher than in differentiated endothelial cells. VEGFR2 and neuropilin transcript levels in EPCs, however, were lower than in differentiated endothelial cells. These results suggest that VEGF/VEGFR1 interactions are important in EPC migration in vitro. We have subcloned VEGFR1 cDNA into a retrovirus vector and have shown by western blot that we can direct increased cellular expression of VEGFR1. In further experiments, we will examine the role of VEGFR1 in human EPC recruitment using murine xenotransplant models of hindlimb ischemia and wound healing. These studies will provide valuable insight towards developing EPCs as cellular therapy to augment blood vessel formation.

Abstract 554: Multimerin2 Influences Vascularization Through Modulation of Perlecan

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Petra E Burgisser ◽  
Dennie Tempel ◽  
Dorien Hermkens ◽  
Stefan Schulte-Merker ◽  
Caroline Cheng ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Blood Vessel ◽  
Angiogenic Factor ◽  
Endothelial Cell Proliferation ◽  
G1 Arrest ◽  
Blood Vessel Formation ◽  
Binding Partner ◽  
Vessel Formation

Vascular development is crucial in normal physiology and pathophysiology, and is in part orchestrated by a dynamic balance between extracellular matrix (ECM) and endothelial cells. The molecular mechanisms that govern this balance and as such play a role in the formation of new blood vessels remain largely unknown. In order to identify new genes involved in blood vessel formation, we performed a genome-wide gene expression array analysis in Flk1+ angioblasts during mouse development using a commercial platform (Affymetrix). Multimerin2 (Mmrn2) expression was found to be upregulated in angioblasts and in the developing vasculature of zebrafish and mice. In vitro , using immunofluorescence, Mmrn2 was detected outside of human aortic endothelial cells (HAECs), were it co-localized with the extracellular matrix components perlecan, laminin and fibronectin. Direct interaction with these proteins was confirmed using a combination of co-immunoprecipitation followed by proteomics (LC-MS), and western blot to identify possible binding partners. Mmrn2 gain-of-function and loss-of-function in vitro studies, using Mmrn2 siRNA and adenoviral constructs likewise decreased and increased the expression of its binding partner perlecan. Perlecan is a well known modulator of the pro-angiogenic factor, FGF2, and is required for further signaling through the FGF receptor. Therefore, Mmrn2 may influence FGF2 signaling through perlecan expression and complex formation. Subsequent in vitro studies using an adenoviral construct to induce Mmrn2 overexpression resulted in a G1-arrest in HAECs (P<0.001, N=8). In FGF2 depleted medium a G1 arrest was also observed (P<0.05, N=3), Mmrn2 overexpression combined with FGF2 depleted medium did not enhance the G1 arrest, suggesting a role of Mmrn2 in FGF2 signaling. In addition, Mmrn2 silencing or overexpression in HAECs led to a loss of ECM organization or improved organization, respectively. In line, the binding partner of Mmrn2, perlecan, has been shown to be involved in stabilization of the ECM. These findings suggest that Mmrn2 plays a role during blood vessel formation by binding to perlecan and the ECM, thereby modulating FGF2 signaling and ECM organization and subsequently, regulating endothelial cell proliferation.

Abstract 528: Nogo-B Receptor is Essential for Primitive Blood Vessel Formation and Vasculature Development in Mouse Embryo

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Zhong Liu ◽  
Ujala Rana ◽  
Baofeng Zhao ◽  
Qing R Miao
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Blood Vessel ◽  
Mouse Embryo ◽  
Knockout Mice ◽  
Embryoid Body ◽  
Blood Vessel Formation ◽  
Vessel Formation ◽  
Body Culture ◽  
Embryonic Lethal

Nogo-B was previously identified as a protein that is expressed in endothelial cells and vascular smooth muscle cells. Nogo-A/B deficient mice show exaggerated neointimal proliferation and abnormal remodeling. Nogo-B receptor (NgBR) is a type I receptor, which was identified as a receptor specific for Nogo-B. Our previous work has shown that Nogo-B and its receptor (NgBR) are essential for chemotaxis and morphogenesis of endothelial cells in vitro and intersomitic vessel formation via Akt pathway in zebrafish. Our recent work reveals that NgBR is a critic membrane scaffold protein required for Ras translocation and activation, which is essential for VEGF-stimulated Ras-PI3K-Akt signaling pathway. Here, we further demonstrate the roles of NgBR in regulating primitive blood vessel formation in embryoid body culture systems and vasculature development in mouse embryo. Murine NgBR gene-targeting embryonic stem cells (ESC) were generated by homologous recombination approaches. Homozygous knockout of NgBR in ESC results in cell apoptosis. Heterozygous knockout of NgBR does not affect ESC cell survival, but reduces the formation and branching of primitive blood vessels in embryoid body culture systems. In addition, our preliminary results show that NgBR homozygous knockout mice are embryonic lethal happened at E6.5 or earlier, and endothelial cell specific NgBR knockout mice are embryonic lethal happened at E11.5 and have severe blood vessel formation defects in embryo. Mechanistically, NgBR has two potential regulatory roles during embryonic vasculature development. NgBR knockdown not only decreases both Nogo-B and VEGF-stimulated endothelial cell migration by abolishing Akt phosphorylation, but also impairs endothelial cell lineage commitment by delaying BMP4 production during the period of mesoderm formation. These results suggest that NgBR may be one of important genes coordinating the vasculature development.

scholarly journals Down-Regulation of miR-101 in Endothelial Cells Promotes Blood Vessel Formation through Reduced Repression of EZH2

PLoS ONE ◽  
2011 ◽  
Vol 6 (1) ◽  
pp. e16282 ◽  
Author(s):  
Michiel Smits ◽  
Shahryar E. Mir ◽  
R. Jonas A. Nilsson ◽  
Petra M. van der Stoop ◽  
Johanna M. Niers ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Vessel ◽  
Down Regulation ◽  
Blood Vessel Formation ◽  
Vessel Formation

scholarly journals Apical secretion of collagen II from endothelial cells precedes blood vessel formation during postnatal vasculogenesis

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Diego F. Alvarez ◽  
Daniel Robinson ◽  
M. Khair ElZarrad ◽  
Troy Stevens ◽  
Judy A. King
Keyword(s):  
Endothelial Cells ◽  
Blood Vessel ◽  
Blood Vessel Formation ◽  
Vessel Formation ◽  
Collagen Ii

scholarly journals Mechanisms of new blood-vessel formation and proliferative heterogeneity of endothelial cells

2020 ◽  
Vol 32 (5) ◽  
pp. 295-305 ◽  
Author(s):  
Hisamichi Naito ◽  
Tomohiro Iba ◽  
Nobuyuki Takakura
Keyword(s):  
Endothelial Cells ◽  
Blood Vessel ◽  
Circulatory System ◽  
Cell Types ◽  
Clonal Expansion ◽  
Waste Products ◽  
Blood Vessel Formation ◽  
Ischemic Disease ◽  
Vessel Formation ◽  
Definition Of

Abstract The vast blood-vessel network of the circulatory system is crucial for maintaining bodily homeostasis, delivering essential molecules and blood cells, and removing waste products. Blood-vessel dysfunction and dysregulation of new blood-vessel formation are related to the onset and progression of many diseases including cancer, ischemic disease, inflammation and immune disorders. Endothelial cells (ECs) are fundamental components of blood vessels and their proliferation is essential for new vessel formation, making them good therapeutic targets for regulating the latter. New blood-vessel formation occurs by vasculogenesis and angiogenesis during development. Induction of ECs termed tip, stalk and phalanx cells by interactions between vascular endothelial growth factor A (VEGF-A) and its receptors (VEGFR1–3) and between Notch and Delta-like Notch ligands (DLLs) is crucial for regulation of angiogenesis. Although the importance of angiogenesis is unequivocal in the adult, vasculogenesis effected by endothelial progenitor cells (EPCs) may also contribute to post-natal vessel formation. However, the definition of these cells is ambiguous and they include several distinct cell types under the simple classification of ‘EPC’. Furthermore, recent evidence indicates that ECs within the intima show clonal expansion in some situations and that they may harbor vascular-resident endothelial stem cells. In this article, we summarize recent knowledge on vascular development and new blood-vessel formation in the adult. We also introduce concepts of EC heterogeneity and EC clonal expansion, referring to our own recent findings.

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