| Title |
Inflammation and N-formyl peptide receptors mediate the angiogenic activity of human vitreous humour in proliferative diabetic retinopathy
|
|---|---|
| Published in |
Diabetologia, January 2017
|
| DOI | 10.1007/s00125-016-4204-0 |
| Pubmed ID | |
| Authors |
Sara Rezzola, Michela Corsini, Paola Chiodelli, Anna Cancarini, Imtiaz M. Nawaz, Daniela Coltrini, Stefania Mitola, Roberto Ronca, Mirella Belleri, Liliana Lista, Dario Rusciano, Mario De Rosa, Vincenzo Pavone, Francesco Semeraro, Marco Presta |
| Abstract |
Angiogenesis and inflammation characterise proliferative diabetic retinopathy (PDR), a major complication of diabetes mellitus. However, the impact of inflammation on the pathogenesis of PDR neovascularisation has not been elucidated. Here, we assessed the capacity of PDR vitreous fluid to induce pro-angiogenic/proinflammatory responses in endothelium and the contribution of the inflammation-related pattern recognition N-formyl peptide receptors (FPRs) in mediating these responses. Pooled and individual pars plana vitrectomy-derived PDR vitreous fluid ('PDR vitreous') samples were assessed in endothelial cell proliferation, motility, sprouting and morphogenesis assays, and for the capacity to induce proinflammatory transcription factor activation, reactive oxygen species production, intercellular junction disruption and leucocyte-adhesion molecule upregulation in these cells. In vivo, the pro-angiogenic/proinflammatory activity of PDR vitreous was tested in murine Matrigel plug and chick embryo chorioallantoic membrane (CAM) assays. Finally, the FPR inhibitors Boc-Phe-Leu-Phe-Leu-Phe (Boc-FLFLF) and Ac-L-Arg-Aib-L-Arg-L-Cα(Me)Phe-NH2 tetrapeptide (UPARANT) were evaluated for their capacity to affect the biological responses elicited by PDR vitreous. PDR vitreous activates a pro-angiogenic/proinflammatory phenotype in endothelial cells. Accordingly, PDR vitreous triggers a potent angiogenic/inflammatory response in vivo. Notably, the different capacity of individual PDR vitreous samples to induce neovessel formation in the CAM correlates with their ability to recruit infiltrating CD45(+) cells. Finally, the FPR inhibitor Boc-FLFLF and the novel FPR antagonist UPARANT inhibit neovessel formation and inflammatory responses triggered by PDR vitreous in the CAM assay. This study provides evidence that inflammation mediates the angiogenic activity of PDR vitreous and paves the way for the development of FPR-targeting anti-inflammatory/anti-angiogenic approaches for PDR therapy. |
X Demographics
The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Germany | 1 | 20% |
| United Kingdom | 1 | 20% |
| Unknown | 3 | 60% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 60% |
| Practitioners (doctors, other healthcare professionals) | 1 | 20% |
| Science communicators (journalists, bloggers, editors) | 1 | 20% |
Mendeley readers
The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 42 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 14% |
| Student > Ph. D. Student | 6 | 14% |
| Student > Bachelor | 5 | 12% |
| Other | 4 | 10% |
| Student > Doctoral Student | 3 | 7% |
| Other | 6 | 14% |
| Unknown | 12 | 29% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 12 | 29% |
| Biochemistry, Genetics and Molecular Biology | 10 | 24% |
| Agricultural and Biological Sciences | 3 | 7% |
| Neuroscience | 2 | 5% |
| Computer Science | 1 | 2% |
| Other | 2 | 5% |
| Unknown | 12 | 29% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 April 2017.
All research outputs
#12,971,722
of 22,959,818 outputs
Outputs from Diabetologia
#4,159
of 5,082 outputs
Outputs of similar age
#200,243
of 421,834 outputs
Outputs of similar age from Diabetologia
#55
of 63 outputs
Altmetric has tracked 22,959,818 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 5,082 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 22.6. This one is in the 17th percentile – i.e., 17% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 421,834 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.
We're also able to compare this research output to 63 others from the same source and published within six weeks on either side of this one. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.