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High-throughput Nitrobenzoxadiazole-labeled Cholesterol Efflux Assay
Published on: January 7, 2019
The negative effect of ANGPTL8 on HDL-mediated cholesterol efflux capacity
Mengdie Luo1, Ziyu Zhang1, Yani Peng2
1Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, No.139, Middle Renmin Road, Changsha, 410011, Hunan, China.
Background:
It is well known that angiopoietin-like protein 8 (ANGPTL8) exerts its effects on lipid metabolism through the inhibition of lipoprotein lipase and subsequent elevation of plasma triglyceride. However, it is not clear whether ANGPTL8 could affect lipid metabolism via other pathways. The study was aimed to investigate the effects of ANGPTL8 on the function of high-density lipoprotein (HDL), which plays a protective role in atherosclerosis progression.
Methods:
Two hundred and ten subjects were recruited. Plasma ANGPTL8 was measured by enzyme-linked immunosorbent assays. Cholesterol efflux capacity was chosen as the biomarker of HDL function and measured via H3-cholesterol loading THP-1 cell models.
Results:
ANGPTL8 exhibited no significant difference between CAD group and nonCAD group, but ANGPTL8 in DM group was significantly higher than that in the nonDM group [568.3 (406.2-836.8) vs 458.2 (356.8-755.6), P = 0.023]. Compared to controls, subjects in CAD group and DM group exhibited significantly lower cholesterol efflux capacity [CAD: 14.58 ± 2.06 vs 12.51 ± 2.83%, P < 0.0001; DM: 13.62 ± 2.57 vs 12.34 ± 3.16%, P = 0.0099]. ANGPTL8 was inversely correlated with cholesterol efflux capacity (r = - 0.188, P < 0.01). Regression analysis revealed that plasma ANGPTL8 was an independent contributor to cholesterol efflux capacity (standardized β = - 0.143, P = 0.023).
Conclusion:
ANGPTL8 presents a negative effect on HDL-mediated cholesterol efflux capacity.
Insights
Angiopoietin-like protein 8 (ANGPTL8) negatively impacts high-density lipoprotein (HDL) function by reducing cholesterol efflux capacity. This finding suggests a novel pathway through which ANGPTL8 influences lipid metabolism and atherosclerosis progression.
Area of Science:
- Lipid metabolism research
- Cardiovascular disease mechanisms
- Biomarker discovery
Background:
- Angiopoietin-like protein 8 (ANGPTL8) is known to affect lipid metabolism by inhibiting lipoprotein lipase, increasing plasma triglyceride levels.
- The precise mechanisms by which ANGPTL8 influences lipid metabolism, particularly its effects on high-density lipoprotein (HDL) function, remain incompletely understood.
- HDL plays a crucial role in protecting against atherosclerosis progression, making its functional integrity a key area of research.
Purpose of the Study:
- To investigate the impact of ANGPTL8 on the functional capacity of HDL.
- To explore potential novel pathways through which ANGPTL8 affects lipid metabolism.
- To determine the relationship between ANGPTL8 levels and HDL-mediated cholesterol efflux capacity in subjects with and without coronary artery disease (CAD) and diabetes mellitus (DM).
Main Methods:
- Recruitment of 210 subjects for the study.
- Quantification of plasma ANGPTL8 levels using enzyme-linked immunosorbent assays (ELISAs).
- Measurement of cholesterol efflux capacity, a key biomarker of HDL function, using a H³-cholesterol loading THP-1 cell model.
Main Results:
- Plasma ANGPTL8 levels were significantly higher in individuals with diabetes mellitus (DM) compared to those without DM.
- Subjects with CAD and DM exhibited significantly reduced cholesterol efflux capacity compared to controls.
- A significant inverse correlation was observed between plasma ANGPTL8 levels and cholesterol efflux capacity (r = -0.188, P < 0.01).
- Regression analysis identified plasma ANGPTL8 as an independent contributor to reduced cholesterol efflux capacity (standardized β = -0.143, P = 0.023).
Conclusions:
- ANGPTL8 exerts a negative influence on HDL-mediated cholesterol efflux capacity.
- This finding suggests a novel mechanism by which ANGPTL8 contributes to dyslipidemia and potentially atherosclerosis.
- Further research is warranted to elucidate the therapeutic implications of targeting ANGPTL8 for cardiovascular health.
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