scholarly journals Venous malformation vessels are improperly specified and hyperproliferative

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0252342
Author(s):  
Michael J. Schonning ◽  
Seung Koh ◽  
Ravi W. Sun ◽  
Gresham T. Richter ◽  
Andrew K. Edwards ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Expression Analysis ◽  
Progenitor Cell ◽  
Venous Malformation ◽  
Biologically Active ◽  
Mural Cell ◽  
Mural Cells ◽  
Clinical Observations ◽  
Cell Expression ◽  
Venous Vasculature

Venous malformations (VMs) are slow-flow malformations of the venous vasculature and are the most common type of vascular malformation with a prevalence of 1%. Germline and somatic mutations have been shown to contribute to VM pathogenesis, but how these mutations affect VM pathobiology is not well understood. The goal of this study was to characterize VM endothelial and mural cell expression by performing a comprehensive expression analysis of VM vasculature. VM specimens (n = 16) were stained for pan-endothelial, arterial, venous, and endothelial progenitor cell proteins; proliferation was assessed with KI67. Endothelial cells in the VM vessels were abnormally orientated and improperly specified, as seen by the misexpression of both arterial and endothelial cell progenitor proteins not observed in control vessels. Consistent with arterialization of the endothelial cells, VM vessels were often surrounded by multiple layers of disorganized mural cells. VM endothelium also had a significant increase in proliferative endothelial cells, which may contribute to the dilated channels seen in VMs. Together the expression analysis indicates that the VM endothelium is misspecified and hyperproliferative, suggesting that VMs are biologically active lesions, consistent with clinical observations of VM progression over time.

VEGF-C regulates lymphangiogenesis and capillary stability by regulation of PDGF-B

2009 ◽  
Vol 297 (5) ◽  
pp. H1685-H1696 ◽  
Author(s):  
Mitsuho Onimaru ◽  
Yoshikazu Yonemitsu ◽  
Takaaki Fujii ◽  
Mitsugu Tanii ◽  
Toshiaki Nakano ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Vascular Endothelial Cells ◽  
Neutralizing Antibody ◽  
Vascular Endothelial ◽  
Mural Cell ◽  
Mural Cells ◽  
Type 3 ◽  
Endothelial Growth Factor ◽  
Capillary Stability

Emerging evidence indicates that the tight communication between vascular endothelial cells and mural cells using platelet-derived growth factor (PDGF)-BB is essential for capillary stabilization during the angiogenic process. However, little is known about the related regulator that determines PDGF-BB expression. Using murine models of therapeutic neovascularization, we here show that a typical lymphangiogenic factor, vascular endothelial growth factor (VEGF)-C, is an essential regulator determining PDGF-BB expression for vascular stabilization via a paracrine mode of action. The blockade of VEGF type 3 receptor (VEGFR3) using neutralizing antibody AFL-4 abrogated FGF-2-mediated limb salvage and blood flow recovery in severely ischemic hindlimb. Interestingly, inhibition of VEGFR3 activity not only diminished lymphangiogenesis, but induced marked dilatation of capillary vessels, showing mural cell dissociation. In these mice, VEGF-C and PDGF-B were upregulated in the later phase after induced ischemia, on day 7, when exogenous FGF-2 expression had already declined, and blockade of VEGFR3 or PDGF-BB activities diminished PDGF-B or VEGF-C expression, respectively. These results clearly indicate that VEGF-C is a critical mediator, not only for lymphangiogenesis, but also for capillary stabilization, the essential molecular mechanism of communication between endothelial cells and mural cells during neovascularization.

scholarly journals Hepatocyte growth factor mediates angiopoietin-induced smooth muscle cell recruitment

Blood ◽  
2006 ◽  
Vol 108 (4) ◽  
pp. 1260-1266 ◽  
Author(s):  
Hanako Kobayashi ◽  
Laura M. DeBusk ◽  
Yael O. Babichev ◽  
Daniel J. Dumont ◽  
Pengnian Charles Lin
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Mural Cell ◽  
Mural Cells ◽  
Hepatocyte Growth ◽  
Vascular Maturation

Abstract Communication between endothelial cells (ECs) and mural cells is critical in vascular maturation. Genetic studies suggest that angiopoietin/Tie2 signaling may play a role in the recruitment of pericytes or smooth muscle cells (SMCs) during vascular maturation. However, the molecular mechanism is unclear. We used microarray technology to analyze genes regulated by angiopoietin-1 (Ang1), an agonist ligand for Tie2, in endothelial cells (ECs). We observed that hepatocyte growth factor (HGF), a mediator of mural cell motility, was up-regulated by Ang1 stimulation. We confirmed this finding by Northern blot and Western blot analyses in cultured vascular endothelial cells. Furthermore, stimulation of ECs with Ang1 increased SMC migration toward endothelial cells in a coculture assay. Addition of a neutralizing anti-HGF antibody inhibited Ang1-induced SMC recruitment, indicating that the induction of SMC migration by Ang1 was caused by the increase of HGF. Interestingly, Ang2, an antagonist ligand of Tie2, inhibited Ang1-induced HGF production and Ang1-induced SMC migration. Finally, we showed that deletion of Tie2 in transgenic mouse reduced HGF production. Collectively, our data reveal a novel mechanism of Ang/Tie2 signaling in regulating vascular maturation and suggest that a delicate balance between Ang1 and Ang2 is critical in this process.

scholarly journals Regenerating vascular mural cells in zebrafish fin blood vessels are not derived from pre-existing ones and differentially require pdgfrb signaling for their development

2021 ◽  
Author(s):  
Arndt F Siekmann ◽  
Elvin Vincent Leonard ◽  
Ricardo Figueroa ◽  
Jeroen Bussmann ◽  
Julio D Amigo ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Tissue Regeneration ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Lineage Tracing ◽  
The Body ◽  
Mural Cell ◽  
Caudal Fin ◽  
Mural Cells

Vascular networks are comprised of endothelial cells and mural cells, which include pericytes and smooth muscle cells. It is well established that new endothelial cells are derived from pre-existing ones during the angiogenic phase of blood vessel growth. By contrast, mural cell ontogeny is less clear with an ongoing debate whether mural cells possess mesenchymal stem cell properties. To elucidate the mechanisms controlling mural cell recruitment during development and tissue regeneration, we studied the formation of zebrafish caudal fin arteries. Mural cells showed morphological heterogeneity: cells colonizing arteries proximal to the body wrapped around them, while those in more distal regions extended protrusions along the proximo-distal vascular axis. Despite these differences, both cell populations expressed platelet-derived growth factor receptor beta (Pdgfrb) and the smooth muscle cell marker myosin heavy chain 11a (Myh11a). Loss of Pdgfrb signalling during development or tissue regeneration resulted in a substantial decrease in mural cells at the vascular front, while those proximal to the body were less affected. Using lineage tracing, we demonstrate that precursor cells located in periarterial regions of the caudal fin and expressing Pgdfrb can give rise to mural cells, while in regeneration newly formed mural cells were not derived from pre-existing ones. Together, our findings reveal conserved roles for pdgfrb signalling in development and regeneration, while at the same time illustrating a limited capacity of mural cells to self-renew or contribute to other cell types during tissue regeneration.

scholarly journals Endothelial cells downregulate apolipoprotein D expression in mural cells through paracrine secretion and Notch signaling

2011 ◽  
Vol 301 (3) ◽  
pp. H784-H793 ◽  
Author(s):  
Mohanasundari Pajaniappan ◽  
Nancy K. Glober ◽  
Simone Kennard ◽  
Hua Liu ◽  
Ning Zhao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Notch Signaling ◽  
Cell Function ◽  
Cell Types ◽  
Fiber Formation ◽  
Cell Contact ◽  
Mural Cell ◽  
Mural Cells ◽  
Paracrine Secretion ◽  
Apolipoprotein D

Endothelial and mural cell interactions are vitally important for proper formation and function of blood vessels. These two cell types communicate to regulate multiple aspects of vessel function. In studying genes regulated by this interaction, we identified apolipoprotein D (APOD) as one gene that is downregulated in mural cells by coculture with endothelial cells. APOD is a secreted glycoprotein that has been implicated in governing stress response, lipid metabolism, and aging. Moreover, APOD is known to regulate smooth muscle cells and is found in abundance within atherosclerotic lesions. Our data show that the regulation of APOD in mural cells is bimodal. Paracrine secretion by endothelial cells causes partial downregulation of APOD expression. Additionally, cell contact-dependent Notch signaling plays a role. NOTCH3 on mural cells promotes the downregulation of APOD, possibly through interaction with the JAGGED-1 ligand on endothelial cells. Our results show that NOTCH3 contributes to the downregulation of APOD and by itself is sufficient to attenuate APOD transcript expression. In examining the consequence of decreased APOD expression in mural cells, we show that APOD negatively regulates cell adhesion. APOD attenuates adhesion by reducing focal contacts; however, it has no effect on stress fiber formation. These data reveal a novel mechanism in which endothelial cells control neighboring mural cells through the downregulation of APOD, which, in turn, influences mural cell function by modulating adhesion.

On-Chip Cell Sorter for Single Cell Expression Analysis

2001 ◽  
pp. 271-273 ◽  
Author(s):  
T. Ichiki ◽  
T. Ujiie ◽  
T. Hara ◽  
Y. Horiike ◽  
K. Yasuda
Keyword(s):  
Single Cell ◽  
Expression Analysis ◽  
Cell Sorter ◽  
On Chip ◽  
Cell Expression

scholarly journals Blood flow boosts BMP signaling to keep vessels in shape

2016 ◽  
Vol 214 (7) ◽  
pp. 793-795 ◽  
Author(s):  
Claudio A. Franco ◽  
Holger Gerhardt
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Blood Flow ◽  
Vascular Remodeling ◽  
Bmp Signaling ◽  
Mural Cells ◽  
Bone Morphogenic Proteins ◽  
Cell Biol ◽  
Suppress Cell Proliferation

Bone morphogenic proteins (BMPs) and blood flow regulate vascular remodeling and homeostasis. In this issue, Baeyens et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201603106) show that blood flow sensitizes endothelial cells to BMP9 signaling by triggering Alk1/ENG complexing to suppress cell proliferation and to recruit mural cells, thereby establishing endothelial quiescence.

Integrative analysis of the human brain mural cell transcriptome

2021 ◽  
pp. 0271678X2110137
Author(s):  
Benjamin D Gastfriend ◽  
Koji L Foreman ◽  
Moriah E Katt ◽  
Sean P Palecek ◽  
Eric V Shusta
Keyword(s):  
Human Brain ◽  
Cell Function ◽  
In Vitro Models ◽  
Molecular Characteristics ◽  
Mural Cell ◽  
Mural Cells ◽  
Brain Pericytes ◽  
Mouse Species ◽  
Cell Transcriptome

Brain mural cells, including pericytes and vascular smooth muscle cells, are important for vascular development, blood-brain barrier function, and neurovascular coupling, but the molecular characteristics of human brain mural cells are incompletely characterized. Single cell RNA-sequencing (scRNA-seq) is increasingly being applied to assess cellular diversity in the human brain, but the scarcity of mural cells in whole brain samples has limited their molecular profiling. Here, we leverage the combined power of multiple independent human brain scRNA-seq datasets to build a transcriptomic database of human brain mural cells. We use this combined dataset to determine human-mouse species differences in mural cell transcriptomes, culture-induced dedifferentiation of human brain pericytes, and human mural cell organotypicity, with several key findings validated by RNA fluorescence in situ hybridization. Together, this work improves knowledge regarding the molecular constituents of human brain mural cells, serves as a resource for hypothesis generation in understanding brain mural cell function, and will facilitate comparative evaluation of animal and in vitro models.

scholarly journals Genome-Wide Identification and Expression Analysis of GA2ox, GA3ox, and GA20ox Are Related to Gibberellin Oxidase Genes in Grape (Vitis Vinifera L.)

Genes ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 680 ◽  
Author(s):  
He ◽  
Liang ◽  
Lu ◽  
Wang ◽  
Liu ◽  
...  
Keyword(s):  
Gene Family ◽  
Real Time ◽  
Expression Analysis ◽  
Bioinformatics Analysis ◽  
Expression Profiles ◽  
Biologically Active ◽  
Vitis Vinifera L ◽  
Genome Database ◽  
Qrt Pcr ◽  
Grape Genome

Gibberellin (GAs) plays the important role in the regulation of grape developmental and growth processes. The bioinformatics analysis confirmed the differential expression of GA2, GA3, and GA20 gibberellin oxidase genes (VvGA2oxs, VvGA3oxs, and VvGA20oxs) in the grape genome, and laid a theoretical basis for exploring its role in grape. Based on the Arabidopsis GA2oxs, GA3oxs, and GA20oxs genes already reported, the VvGA2oxs, VvGA3oxs, and VvGA20oxs genes in the grape genome were identified using the BLAST software in the grape genome database. Bioinformatics analysis was performed using software such as DNAMAN v.5.0, Clustalx, MapGene2Chrom, MEME, GSDS v.2.0, ExPASy, DNAsp v.5.0, and MEGA v.7.0. Chip expression profiles were generated using grape Affymetrix GeneChip 16K and Grape eFP Browser gene chip data in PLEXdb. The expression of VvGA2oxs, VvGA3oxs, and VvGA20oxs gene families in stress was examined by qRT-PCR (Quantitative real-time-PCR). There are 24 GAoxs genes identified with the grape genome that can be classified into seven subgroups based on a phylogenetic tree, gene structures, and conserved Motifs in our research. The gene family has higher codon preference, while selectivity is negative selection of codon bias and selective stress was analyzed. The expression profiles indicated that the most of VvGAox genes were highly expressed under different time lengths of ABA (Abscisic Acid) treatment, NaCl, PEG and 5 °C. Tissue expression analysis showed that the expression levels of VvGA2oxs and VvGA20oxs in different tissues at different developmental stages of grapes were relatively higher than that of VvGA3oxs. Last but not least, qRT-PCR (Real-time fluorescent quantitative PCR) was used to determine the relative expression of the GAoxs gene family under the treatment of GA3 (gibberellin 3) and uniconazole, which can find that some VvGA2oxs was upregulated under GA3 treatment. Simultaneously, some VvGA3oxs and VvGA20oxs were upregulated under uniconazole treatment. In a nutshell, the GA2ox gene mainly functions to inactivate biologically active GAs, while GA20ox mainly degrades C20 gibberellins, and GA3ox is mainly composed of biologically active GAs. The comprehensive analysis of the three classes of VvGAoxs would provide a basis for understanding the evolution and function of the VvGAox gene family in a grape plant.

scholarly journals Does erythropoietin therapy affect circulating endothelial cells in hemodialysis patients?

2020 ◽  
pp. 29-37
Author(s):  
T. Bulduk ◽  
A. U. Yalcin ◽  
O. M. Akay ◽  
S. G. Ozkurt ◽  
H. U. Teke ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Endothelial Progenitor Cell ◽  
Peripheral Blood ◽  
Progenitor Cell ◽  
Hemodialysis Patients ◽  
Circulating Endothelial Cells ◽  
Control Group ◽  
Endothelial Progenitor

Anemia is a common complication of chronic kidney disease (CKD). The most common cause of anemia in CKD is erythropoietin deficiency; and the most important cause of mortality in CKD patients is atherosclerotic vascular complications which are associated with endothelial damage. One of the methods evaluating vascular integrity is the cytometric measurement of circulating endothelial cells and endothelial progenitor cells in peripheral blood. The study aimed to investigate the effects of erythropoietin therapy on endothelial dysfunction by evaluating circulating endothelial cells and endothelial progenitor cells in peripheral blood using the technique of flow cytometry. Methods. A total of 55 hemodialysis patients were evaluated in three groups; those having erythropoietin therapy for at least last 3 months (n = 20) / not having erythropoietin for at least the last 3 months (n = 20) and the patients who started erythropoietin treatment during the study (n = 5). The control group consisted of 20 people. Blood values of the 3rd Group were investigated three times as baseline, 2nd week and 8th week CD34 +, CD105 + cells were evaluated as activated circulating endothelial cells; CD133 +, CD146 + cells were evaluated as activated endothelial progenitor cells. Results. There was no difference between the patients and healthy individuals in terms of circulating endothelial cells and endothelial progenitor cells. In the third group, no differences were observed in circulating endothelial cells / endothelial progenitor cell levels at baseline / 2nd and 8th weeks. There was no correlation between erythropoietin and circulating endothelial cells / endothelial progenitor cells. Conclusion. A correlation is not available between the therapeutic doses of erythropoietin used in hemodialysis patients and circulating endothelial cells / endothelial progenitor cell levels; supratherapeutic doses could change the results.

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