Abstract: SA-PO960
Alanyl-Glutamine Decreases Cellular Injury and Enhances Cytoprotective Responses in Endothelial Cells During PD-Fluid Exposure
Session Information
- Peritoneal Dialysis: Inflammation, Peritoneal Transport
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 703 Dialysis: Peritoneal Dialysis
Authors
- Herzog, Rebecca, Medical University of Vienna, Vienna, Austria
- Bartosova, Maria, Center for Pediatric and Adolescent Medicine, Heidelberg, Germany
- Schmitt, Claus peter, Centre for Pediatric and Adolescent Medicine, Heidelberg, Germany
- Aufricht, Christoph, Medical University of Vienna, Vienna, Austria
- Kratochwill, Klaus, Medical University of Vienna, Vienna, Austria
Background
Vasculopathy, hypervascularization, and diabetes-like damage of vessels are important factors limiting peritoneal dialysis (PD). The composition of all currently available PD fluids (PDF) leads to morphological and functional changes in the peritoneal membrane in adults and infants. During PDF exposure, relevant cellular pathomechanisms might be similar to those in hyperglycaemic diabetic conditions. This study focuses on omics-based characterization of endothelial cell injury and stress responses with or without addition of alanyl-glutamine (AlaGln).
Methods
Protein profiles of primary human umbilical vein endothelial cells (HUVEC) exposed to medium-diluted conventional PDF with or without 8mM AlaGln were analysed by gel-based proteomics. Cell damage was assessed by quantification of lactate-dehydrogenase (LDH) release. Microdissected omental arterioles of children treated with conventional PDFs and healthy controls were analysed with quantitative multiplex mass spectrometry. In-vitro findings were related to PD-induced arteriolar changes based on abundance profiles of proteins identified in both proteomic analyses.
Results
Marked cellular injury of HUVEC after PDF exposure was associated with a molecular landscape of the enriched biological process clusters ‘glucose catabolic process’, ‘cell redox homeostasis’, ‘RNA metabolic process’, ‘protein folding’, ‘regulation of cell death’, and ‘actin cytoskeleton reorganization’ that characterize PDF cytotoxicity and counteracting cellular repair process respectively. Addition of AlaGln to PDF preserved endothelial cell integrity shown by significantly decreased LDH-release and by restored control levels of proteins in PDF perturbed processes, especially enhancing protein folding capacity and response to stress. Comparison to human arterioles confirmed overlapping protein regulation between endothelial cells in-vitro and in-vivo, proving harmful effects of PDFs on endothelial cells leading to drastic changes of the cellular process landscape. Cellular damage and proteome changes in HUVEC were counteracted by AlaGln in-vitro.
Conclusion
In summary, this study elucidates potential mechanisms by which AlaGln exerts cytoprotective effects in PD-induced endothelial cell damage, offering therapeutic targets to reduce side effects of PD.