Tie2 as a novel key factor of microangiopathy in systemic sclerosis

Moritz, F.; Schniering, Janine; Distler, Jörg H W; Gay, Renate E.; Gay, Steffen; Distler, Oliver; Maurer, Britta

doi:10.1186/s13075-017-1304-2

Cited by 26 publications

(19 citation statements)

References 30 publications

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“…However, noting the results of a recent study, there is a reduction in Ang-1/-2 ratio in serum of both pre-SSc and SSc with particular association with DU history [93]. Furthermore, increased vascular expression of Ang-2, reduced Tie2 and comparable Ang-1 in SSc skin versus controls [93] potentially represents a shift towards an anti-angiogenic environment. Progressive study regarding the association of Ang-2 with VEGF-Axxxb isoforms may help map the divergent nature of Ang-2 with VEGF-A expression and the implications of VEGF-A isoforms on angiopoietin function.…”

Section: Additional Mediators Implicated In Enhanced Vegf-a Signalingmentioning

confidence: 86%

“…Under normoxic conditions, Ang-1 aims to maintain vessel stability through Tie2 signaling, whilst Ang-2 is released under hypoxic stress and acts differentially to either facilitate angiogenesis or angio-regression depending on the presence or absence of VEGF-A respectively [93]. Reported circulating levels of angiopoietins and Tie2 are variable in the literature [84,88,[93][94][95][96]. However, noting the results of a recent study, there is a reduction in Ang-1/-2 ratio in serum of both pre-SSc and SSc with particular association with DU history [93].…”

Section: Additional Mediators Implicated In Enhanced Vegf-a Signalingmentioning

confidence: 99%

“…Reported circulating levels of angiopoietins and Tie2 are variable in the literature [84,88,[93][94][95][96]. However, noting the results of a recent study, there is a reduction in Ang-1/-2 ratio in serum of both pre-SSc and SSc with particular association with DU history [93]. Furthermore, increased vascular expression of Ang-2, reduced Tie2 and comparable Ang-1 in SSc skin versus controls [93] potentially represents a shift towards an anti-angiogenic environment.…”

Section: Additional Mediators Implicated In Enhanced Vegf-a Signalingmentioning

confidence: 99%

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The Role of Vascular Endothelial Growth Factor in Systemic Sclerosis

Flower

Barratt

Ward

et al. 2019

CRR

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The pathological hallmarks of Systemic sclerosis (SSc) constitute an inter-related triad of autoimmunity, vasculopathy and tissue remodeling. Many signaling mediators have been implicated in SSc pathology; most focusing on individual components of this pathogenic triad and current treatment paradigms tend to approach management of such as distinct entities. The present review shall examine the role of vascular endothelial growth factor (VEGF) in SSc pathogenesis. We shall outline potential mechanisms whereby differential vascular endothelial growth factor-A (VEGF-A) isoform expression (through conventional and alternative VEGF-A splicing,) may influence the relevant burden of vasculopathy and fibrosis offering novel insight into clinical heterogeneity and disease progression in SSc. Emerging therapeutic approaches targeting VEGF signaling pathways might play an important role in the management of SSc, and differential VEGF-A splice isoform expression may provide a tool for personalized medicine approaches to disease management.

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Section: Additional Mediators Implicated In Enhanced Vegf-a Signalingmentioning

confidence: 86%

Section: Additional Mediators Implicated In Enhanced Vegf-a Signalingmentioning

confidence: 99%

Section: Additional Mediators Implicated In Enhanced Vegf-a Signalingmentioning

confidence: 99%

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The Role of Vascular Endothelial Growth Factor in Systemic Sclerosis

Flower

Barratt

Ward

et al. 2019

CRR

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“…These findings are consistent with elevated Tie2 expression in human RA synovium [ 18 ]. In addition, serum Tie-2 levels were found increased in systemic sclerosis (SSc), another complex disease characterized by widespread microangiopathy [ 19 , 20 ]. Moreover, a dysregulation of Ang/Tie2 was observed in the bleomycin mouse model, reflecting early and inflammatory stages of SSc, which did not apply for the non-inflammatory tight skin mouse model, highlighting the link between Tie-2 and inflammation, as it was observed in our study [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Linking systemic angiogenic markers to synovial vascularization in rheumatoid arthritis

Leblond¹,

Pezet²,

Trouvin³

et al. 2018

PLoS ONE

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BackgroundNeoangiogenesis is a crucial event to promote the development of the hyperplasic proliferative pathologic synovium in Rheumatoid arthritis (RA). Ultrasound (US) is sensitive for detection of power Doppler (PD) vascularization.ObjectiveTo explore the associations between a set of complementary circulating angiogenic markers and a comprehensive US assessment in patients with RA.Patients and methodsSerum levels of eight angiogenic markers were measured by quantitative ELISAs in a total of 125 patients with RA, who were all systematically assessed in parallel by PDUS, performed on 32 joints.ResultsSerum levels of soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and Tie-2 were more likely to be increased in patients with synovial hyperemia detected on at least one joint (Power Doppler grade ≥1). sVCAM-1, Tie-2 and Angiostatin concentrations gradually increased together with the grade of the semiquantitative PDUS scale and concentrations of these three markers were markedly increased in patients with moderate to marked hyperemia (Power Doppler grade 2 and 3). Levels of sVCAM-1, Tie-2, and Angiostatin correlated with a global arthritis sum score, defined by the sum of the semiquantitative PDUS scores for all joints examined. Levels of Tie-2 and Placenta Growth Factor (PlGF) were associated with PDUS features indicating residual disease activity.ConclusionOur results support the relevance of measuring serum levels of vascular markers to evaluate the intensity and extent of synovial vascularization. Angiogenic markers, and particularly Tie-2, could be a valuable surrogate of active synovitis and their place in relation to PDUS in clinical practice deserve further investigation.

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“…41,42 Furthermore, it is currently unknown whether these recently detected Tie2+ cells in the IVD could play a central role in inflammation and IVD degeneration as Tie2 signaling has been linked to mechanism of systemic inflammation and microangio-related pathologies. 43,44 These Tie2+ cells might be a critical element to understand pathologies of the IVD and to develop novel therapeutic perspectives using tissue-engineered constructs.…”

Section: Limitationsmentioning

confidence: 99%

Fluorescence-Activated Cell Sorting Is More Potent to Fish Intervertebral Disk Progenitor Cells Than Magnetic and Beads-Based Methods

Frauchiger

Tekari

May

et al. 2019

Tissue Engineering Part C: Methods

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Low back pain related to intervertebral disk (IVD) degeneration has a major socioeconomic impact on our aging society. Therefore, stem cell therapy to activate self-repair of the IVD remains an exciting treatment strategy. In this respect, tissue-specific progenitors may play a crucial role in IVD regeneration, as these cells are perfectly adapted to this niche. Such a rare progenitor cell population residing in the nucleus pulposus (NP) (NP progenitor cells [NPPCs]) was found positive for the angiopoietin-1 receptor (Tie2+), and was demonstrated to possess self-renewal capacity and in vitro multipotency. Here, we compared three sorting protocols; that is, fluorescence-activated cell sorting (FACS), magnetic-activated cell sorting (MACS), and a mesh-based labelfree cell sorting system (pluriSelect), with respect to cell yield, potential to form colonies (colony-forming units), and in vitro functional differentiation assays for tripotency. The aim of this study was to demonstrate the efficiency of three widespread cell sorting methods for picking rare cells (<5%) and how these isolated cells then behave in downstream functional differentiation in adipogenesis, osteogenesis, and chondrogenesis. The cell yields among the isolation methods differed widely, with FACS presenting the highest yield (5.0%-4.0%), followed by MACS (1.6%-2.9%) and pluriSelect (1.1%-1.0%). The number of colonies formed was not significantly different between Tie2+ and Tie2-NPPCs. Only FACS was able to separate into two functionally different populations that showed trilineage multipotency, while MACS and pluriSelect failed to maintain a clear separation between Tie2+ and Tie2-populations in differentiation assays. To conclude, the isolation of NPPCs was possible with all three sorting methods, while FACS was the preferred technique for separation of functional Tie2+ cells.

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Tie2 as a novel key factor of microangiopathy in systemic sclerosis

Cited by 26 publications

References 30 publications

The Role of Vascular Endothelial Growth Factor in Systemic Sclerosis

The Role of Vascular Endothelial Growth Factor in Systemic Sclerosis

Linking systemic angiogenic markers to synovial vascularization in rheumatoid arthritis

Fluorescence-Activated Cell Sorting Is More Potent to Fish Intervertebral Disk Progenitor Cells Than Magnetic and Beads-Based Methods

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