Increased carbamylation level of HDL in end-stage renal disease: carbamylated-HDL attenuated endothelial cell
Jia Teng Sun1, Ke Yang2, Lin Lu1
1Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
Insights
Carbamylated high-density lipoprotein (C-HDL) is elevated in end-stage renal disease (ESRD) and impairs endothelial cell repair. This study reveals C-HDL
Area of Science:
- Cardiovascular Research
- Nephrology
- Biochemistry
Background:
- Carbamylation is implicated in cardiovascular disease (CVD) progression in end-stage renal disease (ESRD) patients.
- The specific biological impact of carbamylated high-density lipoprotein (C-HDL) on endothelial repair in ESRD remains poorly understood.
- Understanding C-HDL's role is crucial for developing targeted therapies for CVD in ESRD patients.
Purpose of the Study:
- To quantify HDL carbamylation levels in ESRD patients.
- To investigate the effects of C-HDL on endothelial cell repair functions, including migration, proliferation, and angiogenesis.
- To explore the underlying mechanisms, such as changes in HDL-associated paraoxonase 1 activity and key signaling pathways.
Main Methods:
- HDL was isolated from healthy controls and ESRD patients.
- HDL carbamylation levels were measured using ELISA.
- In vitro experiments assessed C-HDL's impact on human arterial endothelial cell migration, proliferation, and angiogenesis.
- HDL-associated paraoxonase 1 activity was determined spectrophotometrically.
- Expression of VEGF receptor 2 and scavenger receptor class B type I was analyzed.
Main Results:
- HDL carbamylation levels were significantly higher in ESRD patients compared to healthy controls, correlating positively with blood urea concentration.
- In vitro, C-HDL markedly inhibited endothelial cell migration, angiogenesis, and proliferation.
- HDL-associated paraoxonase 1 activity was reduced in ESRD patients' HDL and negatively correlated with carbamylation levels.
- C-HDL suppressed VEGF receptor 2 and scavenger receptor class B type I signaling pathways.
Conclusions:
- This study demonstrates significantly increased HDL carbamylation in ESRD patients.
- Carbamylated HDL exerts detrimental effects on endothelial cell repair mechanisms.
- Reduced paraoxonase 1 activity and suppressed key signaling pathways contribute to C-HDL's adverse effects in ESRD.
Abstract:
It is thought that carbamylated modification plays a crucial role in the development and progression of cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD). However, information on the biological effects of carbamylated high-density lipoprotein (C-HDL) in ESRD is poor. The present study investigated the carbamylation level of HDL in ESRD and the effects of C-HDL on endothelial repair properties. HDL was isolated from healthy control subjects (n = 22) and patients with ESRD (n = 30). The carbamylation level of HDL was detected using ELISA. Isolated C-HDL for use in tissue culture experiments was carbamylated in vitro to a similar extent to that observed in ESRD. Human arterial endothelial cells were treated with C-HDL or native HDL to assess their migration, proliferation, and angiogenesis properties. HDL-associated paraoxonase 1 activity was also determined by spectrophotometry assay. Compared with healthy control subjects, the carbamylation level of HDL in ESRD patients was increased and positively correlated with blood urea concentration. In vitro, C-HDL significantly inhibited migration, angiogenesis, and proliferation in endothelial cells. Mechanistic studies revealed that HDL-associated paraoxonase 1 activity was decreased and negatively correlated with the carbamylation level of HDL in ESRD patients. In addition, C-HDL suppressed the expression of VEGF receptor 2 and scavenger receptor class B type I signaling pathways in endothelial cells. In conclusion, the present study identified a significantly increased carbamylation level of HDL in ESRD. Furthermore, C-HDL inhibited endothelial cell repair functions.
More Related Videos
08:45LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring
Published on: November 17, 2018
07:29Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein
Published on: October 12, 2017
Related Concept Videos
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
01:28Chronic Kidney Disease III: Interprofessional Care
01:24Hemodialysis II: Procedure and Complications
01:26Coronary Artery Disease IV: Preventive Measures
01:26Atherosclerosis III: Management
01:24Chronic Kidney Disease II: Clinical Manifestations