Angiopoietin-2: Ein neuer serologischer Marker für das cholangiozelluläre Karzinom

Objective: A retinal vein occlusion (RVO) is a relatively common retinal vascular disorder especially in the elder-ly. Many experiments have been performed on patients with a RVO but performing any type of experiments and especially longitudinal experiments on humans is difficult if not impossible on ethical grounds. Therefore, we have created a retinal vein occlusion (RVO) model by laser irradiation of cynomolgus monkeysafter an intravenous injection of rose bengal. Weevaluated the pathological changes of the retina, and the effects of ranibizumab, an anti-vascular endothelial growth factor (VEGF) antibody, on the characteristics of the RVO. Methods: The integrity of the vascular system was evaluated by fluorescein angiography (FA), and the retinal thickness and volume were determined by optical coherence tomography (OCT). The cytokines and growth factors in the aqueous humor were identified by multiplex profiling. Results: Our results showed that ranibizumab decreased the degree of vascular leakage and retinal edema at 1-3 days (acute phase) and 3-7 days (subacute phase), and suppressed foveal thinning at 28-42 days (chronic phase) after the laser irradia-tion. Ranibizumab also decreased the area of the foveal avascular zone, and the area was negatively and significantly corre-lated with the thickness of the ganglion cell layer (GCL) complex. Furthermore, ranibizumab reduced the increased expres-sion of VEGF in the aqueous humour, but did not affect the expressions of interleukin-6 (IL-6), monocyte chemotactic pro-tein-1 (MCP-1), angiopoietin-1 (ANG-1), or angiopoietin-2 (ANG-2).Thesefindings suggest that ranibizumab attenuates the retinal edema and subsequent retinal atrophy in partby neutralizing VEGF. However, other cytokines and growth factors were also affected by the ranibizumab which suggests that not only VEGF but also other unidentified agents might play a role in the pathogenesis of the RVO. Conclusion: We have created a non-human primate RVO model, which resembles the clinical RVO pathology. In this model, an injection of ranibizumab leads to a reduction in the vascular leakage and the retinal thickness and volume by blockingthe expression of VEGF. Our model might be useful for investigating the pathological mechanisms of RVOs and explore new therapeutic agents for RVO.

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Removal of elevated circulating angiopoietin-2 by plasma exchange – A pilot study in critically ill patients with thrombotic microangiopathy and anti-glomerular basement membrane disease

Thrombosis and Haemostasis ◽

10.1160/th10-02-0138 ◽

2010 ◽

Vol 104 (11) ◽

pp. 1038-1043 ◽

Cited By ~ 8

Author(s):

Carsten Hafer ◽

Jan Kielstein ◽

Marion Haubitz ◽

Hermann Haller ◽

Svjetlana Lovric ◽

...

Keyword(s):

Basement Membrane ◽

Plasma Exchange ◽

Critically Ill ◽

Glomerular Basement Membrane ◽

Critically Ill Patients ◽

Plasma Levels ◽

Vascular Inflammation ◽

Endothelial Damage ◽

Healthy Controls ◽

Angiopoietin 2

SummaryIn critically ill patients, the massive release of angiopoietin-2 (Ang-2) from Weibel-Palade bodies interferes with protective angiopoietin-1 (Ang-1)/Tie2 signalling in endothelial cells, thus leading to vascular inflammation and subsequent organ-dysfunction. We hypothesised that plasma exchange (PE) is efficient for lowering excess Ang-2 levels in critically ill patients with thrombocytic microangiopathy (TMA) or anti-glomerular basement membrane (anti-GBM) disease. Plasma Ang-1 and Ang-2 were measured by immuno-luminometric assays in patients with TMA (n=9) or anti-GBM disease (n=4) before and after up to four PE sessions. Twenty apparently healthy volunteers served as controls. Median (IQR) plasma levels of Ang-2 were markedly increased in patients with TMA (7.3 (2.4–21.1) ng/ml) and anti-GBM disease (5.8 (3.4–7.0) ng/ml) compared to healthy controls (1.0 (0.9–1.4) ng/ml, p <0.001). Moreover, Ang-1 plasma levels were decreased in both, TMA (1.02 (0.62–1.62) ng/ml) and anti-GBM disease patients (0.74 (0.59–3.62) ng/ml) compared to healthy controls (2.5 (1.93–3.47) ng/ ml, p <0.005). During a total of 32 treatments, PE effectively lowered elevated mean (SD) Ang-2 plasma levels by 36.7 ± 19.6 % per treatment (p <0.0001), whereas low Ang-1 plasma levels remained unchanged (0.3 ± 58.5 %; p =0.147). Ang-2 levels declined to almost normal values during ≤4 PE treatments (Friedman´s test p <0.0001). PE is an effective method to remove excess circulating Ang-2. It remains to be elucidated if the removal of Ang-2 is crucial to ameliorate endothelial damage in critically ill patients with severely altered endothelial integrity.

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Time course of angiopoietin-2 release during experimental human endotoxemia and sepsis

Critical Care ◽

10.1186/cc7866 ◽

2009 ◽

Vol 13 (3) ◽

pp. R64 ◽

Cited By ~ 61

Author(s):

Philipp Kumpers ◽

Matijs van Meurs ◽

Sascha David ◽

Grietje Molema ◽

Johan Bijzet ◽

...

Keyword(s):

Time Course ◽

Human Endotoxemia ◽

Angiopoietin 2

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Plasma angiopoietin-2 is associated with age-related deficits in cognitive sub-scales in Ugandan children following severe malaria

Malaria Journal ◽

10.1186/s12936-020-03545-6 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Benson J. Ouma ◽

Paul Bangirana ◽

John M. Ssenkusu ◽

Dibyadyuti Datta ◽

Robert O. Opoka ◽

...

Keyword(s):

Severe Malaria ◽

Parental Education ◽

Preschool Education ◽

Kidney Injury ◽

Malaria Episode ◽

Enzyme Linked Immunosorbent Assay ◽

Testing Time ◽

Age Related ◽

Angiopoietin 2 ◽

The Relationship

Abstract Background Elevated angiopoietin-2 (Angpt-2) concentrations are associated with worse overall neurocognitive function in severe malaria survivors, but the specific domains affected have not been elucidated. Methods Ugandan children with severe malaria underwent neurocognitive evaluation a week after hospital discharge and at 6, 12 and 24 months follow-up. The relationship between Angpt-2 concentrations and age-adjusted, cognitive sub-scale z-scores over time were evaluated using linear mixed effects models, adjusting for disease severity (coma, acute kidney injury, number of seizures in hospital) and sociodemographic factors (age, gender, height-for-age z-score, socio-economic status, enrichment in the home environment, parental education, and any preschool education of the child). The Mullen Scales of Early Learning was used in children < 5 years and the Kaufman Assessment Battery for Children 2nd edition was used in children ≥ 5 years of age. Angpt-2 levels were measured on admission plasma samples by enzyme-linked immunosorbent assay. Adjustment for multiple comparisons was conducted using the Benjamini–Hochberg Procedure of False Discovery Rate. Results Increased admission Angpt-2 concentration was associated with worse outcomes in all domains (fine and gross motor, visual reception, receptive and expressive language) in children < 5 years of age at the time of severe malaria episode, and worse simultaneous processing and learning in children < 5 years of age at the time of severe malaria who were tested when ≥ 5 years of age. No association was seen between Angpt-2 levels and cognitive outcomes in children ≥ 5 years at the time of severe malaria episode, but numbers of children and testing time points were lower for children ≥ 5 years at the time of severe malaria episode. Conclusion Elevated Angpt-2 concentration in children with severe malaria is associated with worse outcomes in multiple neurocognitive domains. The relationship between Angpt-2 and worse cognition is evident in children < 5 years of age at the time of severe malaria presentation and in selected domains in older years.

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