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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 22, 2023 |
| Title |
Calprotectin blockade inhibits long-term vascular pathology following peritoneal dialysis-associated bacterial infection. [2] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by RT-PCR
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| Summary |
Bacterial infections and the concurrent inflammation have been associated with increased long-term cardiovascular (CV) risk. In patients receiving peritoneal dialysis (PD), bacterial peritonitis is a common occurrence, and each episode further increases late CV mortality risk. However, the underlying mechanism(s) remains to be elucidated before safe and efficient anti-inflammatory interventions can be developed. Damage-Associated Molecular Patterns (DAMPs) have been shown to contribute to the acute inflammatory response to infections, but a potential role for DAMPs in mediating long-term vascular inflammation and CV risk following infection resolution in PD, has not been investigated. We found that bacterial peritonitis in mice that resolved within 24h led to CV disease-promoting systemic and vascular immune-mediated inflammatory responses that were maintained up to 28 days. These included higher blood proportions of inflammatory leukocytes displaying increased adhesion molecule expression, higher plasma cytokines levels, and increased aortic inflammatory and atherosclerosis-associated gene expression. These effects were also observed in infected nephropathic mice and amplified in mice routinely exposed to PD fluids. A peritonitis episode resulted in elevated plasma levels of the DAMP Calprotectin, both in PD patients and mice, here the increase was maintained up to 28 days. In vitro, the ability of culture supernatants from infected cells to promote key inflammatory and atherosclerosis-associated cellular responses, such as monocyte chemotaxis, and foam cell formation, was Calprotectin-dependent. In vivo, Calprotectin blockade robustly inhibited the short and long-term peripheral and vascular consequences of peritonitis, thereby demonstrating that targeting of the DAMP Calprotectin is a promising therapeutic strategy to reduce the long-lasting vascular inflammatory aftermath of an infection, notably PD-associated peritonitis, ultimately lowering CV risk.
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| Overall design |
Peritonitis was induced in mice by administration of live Staphyloccocus epidermidis i.p. In addition, mice did or did not (PBS administered) receive daily i.p. Peritoneal Dialysis Fluid (PDF) exposure, staring 14 days before and lasting 28 days after peritonitis induction. At Day 28, aortas from at least n=3 mice / group were collected and analysed by RT2 profiler array
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| Contributor(s) |
Cetin E, Mazzarino M, Raby A |
| Citation(s) |
38094743 |
| Submission date |
Oct 24, 2023 |
| Last update date |
Jan 02, 2024 |
| Contact name |
Anne-Catherine Raby |
| E-mail(s) |
rabya@cardiff.ac.uk
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| Phone |
02920687324
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| Organization name |
Cardiff University
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| Street address |
Heath Park, Academic Avenue
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| City |
Cardiff |
| State/province |
Cardiff |
| ZIP/Postal code |
CF14 4XN |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL29397 |
RT² Profiler™ PCR Array Mouse Atherosclerosis |
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| Samples (4)
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| GSM7855464 |
Non-infected Control mice |
| GSM7855465 |
Control + S.epidermidis peritonitis |
| GSM7855466 |
Non infected PDF-exposed mice (i.p. catheter fitter, daily PDF administration) |
| GSM7855467 |
PDF-exposed mice + S.epidermidis peritonitis |
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| This SubSeries is part of SuperSeries: |
| GSE246102 |
Calprotectin blockade inhibits long-term vascular pathology following peritoneal dialysis-associated bacterial infection. |
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| Relations |
| BioProject |
PRJNA1031553 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE246101_GEO_mouse_atherosclerosis_PDF_exposure_aortas.xls.gz |
29.5 Kb |
(ftp)(http) |
XLS |
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