Analysis of soluble angiogenic factors in Crohn’s disease: a preliminary study

Pousa, I.; Jímenez, José; Mora, X. Salcedo; Abreu, María T.; Otero, R. Moreno; Gisbert, Javier P.

doi:10.1157/13111682

Cited by 10 publications

(9 citation statements)

References 20 publications

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“…VEGF‐A may serve as an intermediary between angiogenic stimulation, lymphangiogenic stimulation, and cell‐mediated immune responses. The increased levels of VEGF in chronic IBD have also been confirmed by other studies in which significantly higher VEGF serum levels were observed in patients with active CD and UC than in controls 5, 37–40. On the other hand, Kapsoritakis et al41 reported that plasma VEGF levels were lower and immunostaining intensity weaker in patients with active CD than in healthy controls.…”

Section: Lymphangiogenic Growth Factors In Ibdsupporting

confidence: 52%

“…Median serum Ang‐2 and Tie‐2 levels have been found to be significantly higher in both UC and CD patients than in healthy controls. CD patients with active disease had significantly higher levels of Ang‐2 compared with patients with nonactive disease 34, 39, 75. Although these studies do not provide enough evidence of the role of the angiopoietin system in the development of lymphatic vessels in IBD patients, this could show us how angiopoietins are involved in this process.…”

Section: Lymphangiogenic Growth Factors In Ibdmentioning

confidence: 84%

“…VEGF‐A lymphangiogenesis signaling pathway receptor VEGFR‐2 has been observed to be increased both in samples from patients with IBD and in mice with DSS‐induced colitis 40 ; however, Pousa et al34, 39, 40 found no differences in VEGFR‐2 serum levels between IBD patients and healthy controls.…”

Section: Lymphangiogenic Growth Factors In Ibdmentioning

confidence: 98%

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Role of growth factors in the development of lymphangiogenesis driven by inflammatory bowel disease

Linares

Gisbert

2011

Inflammatory Bowel Diseases

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Studies on angiogenesis and lymphangiogenesis have gained special relevance in research into factors potentially influencing the pathogenesis and course of inflammatory bowel disease (IBD). The results of the few existing studies on the distribution and density of lymphatic vessels and blood vessels in the context of IBD are controversial. Studies using the specific lymphatic marker podoplanin have revealed a significantly large number of lymphatic vessels in the colonic mucosa of patients with ulcerative colitis and Crohn's disease (compared to patients with normal mucosa), whereas other authors have found no significant differences. However, the role of vascular endothelial growth factor (VEGF) tyrosine-kinase receptor 3 (VEGFR-3) in the onset of IBD has not been analyzed. In recent years new biochemical, molecular, and immunohistochemical studies indicate that several families of growth factors, such as the VEGF family and their receptors, fibroblast growth factor-2, platelet-derived growth factor-BB, hepatocyte growth factor, the angiopoietin system, and integrins may play an important role in the onset of IBD. To date, no comparative studies have analyzed these growth factors and specific lymphatic markers. We examine how growth factors are involved in the development of pathological lymphangiogenesis in patients with IBD and determine whether they play a crucial role in disease exacerbation.

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Section: Lymphangiogenic Growth Factors In Ibdsupporting

confidence: 52%

Section: Lymphangiogenic Growth Factors In Ibdmentioning

confidence: 84%

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Role of growth factors in the development of lymphangiogenesis driven by inflammatory bowel disease

Linares

Gisbert

2011

Inflammatory Bowel Diseases

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“…For example, sTie2 plasma levels are elevated in Crohn's disease (10), critical limb ischemia (16), and acute myocardial infarction (25). Lowering of sTie2 is furthermore a prognostic marker in the treatment of renal carcinoma (19), a tumor type associated with elevated VEGF production, which was identified as one of the triggers for Tie2 shedding from the endothelial membrane (15).…”

Section: Discussionmentioning

confidence: 99%

Shock-induced stress induces loss of microvascular endothelial Tie2 in the kidney which is not associated with reduced glomerular barrier function

Meurs

Kurniati²,

Wulfert³

et al. 2009

American Journal of Physiology-Renal Physiology

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Both hemorrhagic shock and endotoxemia induce a pronounced vascular activation in the kidney which coincides with albuminuria and glomerular barrier dysfunction. We hypothesized that changes in Tie2, a vascular restricted receptor tyrosine kinase shown to control microvascular integrity and endothelial inflammation, underlie this loss of glomerular barrier function. In healthy murine and human kidney, Tie2 is heterogeneously expressed in all microvascular beds, although to different extents. In mice subjected to hemorrhagic and septic shock, Tie2 mRNA and protein were rapidly, and temporarily, lost from the renal microvasculature, and normalized within 24 h after initiation of the shock insult. The loss of Tie2 protein could not be attributed to shedding as both in mice and healthy volunteers subjected to endotoxemia, sTie2 levels in the systemic circulation did not change. In an attempt to identify the molecular control of Tie2, we activated glomerular endothelial cell cultures and human kidney slices in vitro with LPS or TNF-alpha, but did not observe a change in Tie2 mRNA levels. In parallel to the loss of Tie2 in vivo, an overt influx of neutrophils in the glomerular compartment, which coincided with proteinuria, was seen. As neutrophil-endothelial cell interactions may play a role in endothelial adaptation to shock, and these effects cannot be mimicked in vitro, we depleted neutrophils before shock induction. While this neutrophil depletion abolished proteinuria, Tie2 was not rescued, implying that Tie2 may not be a major factor controlling maintenance of the glomerular filtration barrier in this model.

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“…In addition, the cells and tissues providing the pro-lymphatic VEGFs that mediate IBD-associated lymphangiogenesis remain to be identified. In IBD patients, increased levels of lymphatic growth factors VEGF-A, VEGF-C, and VEGF-D have been reported in serum and mucosa culture supernatants ( Algaba et al, 2013 ; Bousvaros et al, 1999 ; D'Alessio et al, 2014 ; Duenas Pousa et al, 2007 ; Kanazawa et al, 2001 ; Pousa et al, 2008 ). Peripheral blood mononuclear cells ( Griga et al, 1999a ,c ), intestinal mucosa ( Griga et al, 1999a , 2002 ), adipose tissue ( Schaffler et al, 2006 ), and fibroblasts ( Beddy et al, 2004 ) have all been suggested to provide VEGF-A in IBD and may be particularly important for IBD-associated angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

A zebrafish model of inflammatory lymphangiogenesis

et al. 2015

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Inflammatory bowel disease (IBD) is a disabling chronic inflammatory disease of the gastrointestinal tract. IBD patients have increased intestinal lymphatic vessel density and recent studies have shown that this may contribute to the resolution of IBD. However, the molecular mechanisms involved in IBD-associated lymphangiogenesis are still unclear. In this study, we established a novel inflammatory lymphangiogenesis model in zebrafish larvae involving colitogenic challenge stimulated by exposure to 2,4,6-trinitrobenzenesulfonic acid (TNBS) or dextran sodium sulphate (DSS). Treatment with either TNBS or DSS resulted in vascular endothelial growth factor receptor (Vegfr)-dependent lymphangiogenesis in the zebrafish intestine. Reduction of intestinal inflammation by the administration of the IBD therapeutic, 5-aminosalicylic acid, reduced intestinal lymphatic expansion. Zebrafish macrophages express vascular growth factors vegfaa, vegfc and vegfd and chemical ablation of these cells inhibits intestinal lymphatic expansion, suggesting that the recruitment of macrophages to the intestine upon colitogenic challenge is required for intestinal inflammatory lymphangiogenesis. Importantly, this study highlights the potential of zebrafish as an inflammatory lymphangiogenesis model that can be used to investigate the role and mechanism of lymphangiogenesis in inflammatory diseases such as IBD.

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Analysis of soluble angiogenic factors in Crohn’s disease: a preliminary study

Cited by 10 publications

References 20 publications

Role of growth factors in the development of lymphangiogenesis driven by inflammatory bowel disease

Role of growth factors in the development of lymphangiogenesis driven by inflammatory bowel disease

Shock-induced stress induces loss of microvascular endothelial Tie2 in the kidney which is not associated with reduced glomerular barrier function

A zebrafish model of inflammatory lymphangiogenesis

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