Abstract: PO1825
Effect of Uremia on Endothelial Cell Damage Is Mediated by Excessive Neutrophil Extracellular Trap Formation
Session Information
- Hypertension and CVD: Mechanisms
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Kim, Jwa-kyung, Hallym University Sacred Heart Hospital, Anyang, Gyeonggi-do, Korea (the Republic of)
- Lee, Hoi Woul, Hallym University Sacred Heart Hospital, Anyang, Gyeonggi-do, Korea (the Republic of)
- Kim, Sung gyun, Hallym University Sacred Heart Hospital, Anyang, Gyeonggi-do, Korea (the Republic of)
Background
Uremia is a clinical syndrome characterized by accumulation of various uremic toxins and associated metabolic abnormalities in chronic kidney disease (CKD). Patients with CKD are at increased risk for cardiovascular (CV) disease and death, and endothelial dysfunction may be a key uremia-specific risk factor. However, the mechanism by which uremia influences endothelial dysfunction is still unclear. We report a role for excessive neutrophil extracellular trap (NET) formation induced by uremic serum on endothelial cell (EC) injury.
Methods
Plasma nucleosome and myeloperoxidase-DNA, representative markers of in vivo NETs, and the intracellular adhesion molecule (ICAM)-1 level were measured in incident hemodialysis (HD) patients and healthy volunteer (HV), and their prognostic role was evaluated. For in vitro study, we differentiated HL-60 cells into neutrophil-like cells (dHL-60) by applying retinoic acid, and the effect of uremic serum on dHL-60 and ECs were determined.
Results
The amount of in vivo NETs were significantly higher in incident HD patients compared to HV, and the markers were strongly associated with ICAM-1 levels. In particular, nucleosome and ICAM-1 levels were independent predictors of a composite endpoint, all-cause mortality or vascular access failure. In vitro, uremic serum derived from HD patients showed significantly increased NETs formation from dHL-60, and these NETs significantly decreased EC viability and induced apoptosis. In addition, the ICAM-1 level in HUVEC supernatant was significantly increased by uremic serum-induced NETs compared to control serum-induced NETs.
Conclusion
Dysregulated neutrophil activities in the uremic milieu may play a key role in endothelial damage and vascular inflammatory responses.