Both plasma basic carboxypeptidases, carboxypeptidase B2 and carboxypeptidase N, regulate vascular leakage activity in mice

Author(s):  
Qin Zhou ◽  
Lei Zhao ◽  
Zhifei Shao ◽  
Paul Declerck ◽  
Lawrence L.K. Leung ◽  
...  





2018 ◽  
Author(s):  
Shih-Hung Tsai ◽  
Po-Hsun Huang ◽  
Yu-Juei Hsu ◽  
Yen-Wen Chen ◽  
Jen-Chun Wang ◽  
...  


2020 ◽  
Vol 17 ◽  
Author(s):  
Satoshi Inagaki ◽  
Masamitsu Shimazawa ◽  
Wataru Otsu ◽  
Tomoaki Araki ◽  
Yosuke Numata ◽  
...  

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.



2021 ◽  
Vol 22 (4) ◽  
pp. 1682
Author(s):  
Bálint Botz ◽  
Gábor Kriszta ◽  
Kata Bölcskei ◽  
Ádám István Horváth ◽  
Attila Mócsai ◽  
...  

Capsaicin-sensitive peptidergic sensory nerves play complex, mainly protective regulatory roles in the inflammatory cascade of the joints via neuropeptide mediators, but the mechanisms of the hyperacute arthritis phase has not been investigated. Therefore, we studied the involvement of these afferents in the early, “black box” period of a rheumatoid arthritis (RA) mouse model. Capsaicin-sensitive fibres were defunctionalized by pretreatment with the ultrapotent capsaicin analog resiniferatoxin and arthritis was induced by K/BxN arthritogenic serum. Disease severity was assessed by clinical scoring, reactive oxygen species (ROS) burst by chemiluminescent, vascular permeability by fluorescent in vivo imaging. Contrast-enhanced magnetic resonance imaging was used to correlate the functional and morphological changes. After sensory desensitization, both early phase ROS-burst and vascular leakage were significantly enhanced, which was later followed by the increased clinical severity scores. Furthermore, the early vascular leakage and ROS-burst were found to be good predictors of later arthritis severity. We conclude that the anti-inflammatory role of peptidergic afferents depends on their activity in the hyperacute phase, characterized by decreased cellular and vascular inflammatory components presumably via anti-inflammatory neuropeptide release. Therefore, these fibres might serve as important gatekeepers in RA.



FEBS Open Bio ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 801-813 ◽  
Author(s):  
Jung Min Ha ◽  
Seo Yeon Jin ◽  
Hye Sun Lee ◽  
Farzaneh Vafaeinik ◽  
Yoo Jin Jung ◽  
...  




Sign in / Sign up

Export Citation Format

Share Document