Calprotectin blockade inhibits long-term vascular pathology following peritoneal dialysis-associated bacterial infection. [2]
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ABSTRACT:
PROVIDER: PRJNA1031553 | ENA |
REPOSITORIES: ENA
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Project description:Calprotectin blockade inhibits long-term vascular pathology following peritoneal dialysis-associated bacterial infection.
| PRJNA1031548 | ENA
Project description:Calprotectin blockade inhibits long-term vascular pathology following peritoneal dialysis-associated bacterial infection. [1]
| PRJNA1031551 | ENA
Project description: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.
2023-11-22 | GSE246100 | GEO
Project description: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.
2023-11-22 | GSE246101 | GEO
Project description:Transcriptome analysis of two population of peritoneal mononuclear phagocytes (CD14+ macrophages and CD1c+ dendritic cells) in peritoneal dialysis effluent from stable (infection-free) peritoneal dialysis patients.
2017-01-23 | E-MTAB-5439 | biostudies-arrayexpress
Project description:The complete systemic deregulated biological network in peritoneal dialysis (PD) patients is still only partially defined. High-throughput/omics techniques may offer the possibility to analyze the main biological fingerprints associated with this clinical condition. For the transcriptomic part of the study, we analyzed new data from 10 patients undergoing peritoneal dialysis .
2023-12-31 | E-MTAB-12875 | biostudies-arrayexpress
Project description:Biological Determinants of Peritoneal Dialysis Outcomes
| PRJNA860262 | ENA
Project description:Biological Determinants of Peritoneal Dialysis Outcomes
| PRJNA860263 | ENA
Project description:Long-term peritoneal dialysis (PD) is associated with functional and structural alterations of the peritoneal membrane. Inflammation may be the key moment and consequently fibrosis, the end result of chronic inflammatory reaction. The objective of the study was to identify genes involved in peritoneal alterations during PD by comparing transcriptome of peritoneal cells in short- and long-term PD patients. Peritoneal effluent of the long-dwell of stable PD patients was centrifuged to obtain peritoneal cells. Gene expression profiling of peritoneal cells using microarray between short- and long-term PD patients was compared. Based on microarray analysis 31 genes for RT-qPCR validation were chosen. A 4-hour peritoneal equilibration test (PET) was performed on the day after the long dwell. Transport parameters and proteins appearance rates were assessed. Genes involved in the immune system process, immune response, cell activation, leuko- and lymphocyte activation were found to be substantially up-regulated in the long-term group. RT-qPCR validation showed higher expression of CD24 (CD24 molecule), LY9 (lymphocyte antigen 9 ), TNFRSF4 (tumor necrosis factor receptor superfamily, member 4), CD79A (CD79a molecule, immunoglobulin-associated alpha), CCR7 (chemokine (C-C motif) receptor 7), CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1) and IL2RA (interleukin 2 receptor, alpha) in long-term PD patients, CD24 having the best discrimination ability between short- and long-term treatment. A relationship between CD24 expression and genes for collagen and matrix formation was shown. Activation of CD24 provoked by pseudohypoxia due to extremely high glucose concentrations in dialysis solutions might play the key role in the development of peritoneal membrane alterations.
2019-01-24 | GSE125498 | GEO
Project description: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.
| S-EPMC10716465 | biostudies-literature