2,3,4′,5-tetrahydroxystilbene-2-O-β-d-glycoside attenuates atherosclerosis in apolipoprotein E-deficient mice: role of reverse cholesterol transport

2018 ◽  
Vol 96 (1) ◽  
pp. 8-17 ◽  
Author(s):  
Xuemeng Chen ◽  
Kun Tang ◽  
Yi Peng ◽  
XiaoLe Xu
Keyword(s):  
Reverse Cholesterol Transport ◽  
Cholesterol Efflux ◽  
Cholesterol Metabolism ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Lipoprotein Cholesterol ◽  
Cholesterol Transport ◽  
Positive Role ◽  
Protein Expressions

The aim of this study was to evaluate the potential effects of 2,3,4′,5-tetrahydroxystilbene-2-O-β-d-glucoside (TSG) on the development of atherosclerotic plaque in ApoE−/− mice, and explore the mechanisms involved. Our data showed that after 8 weeks of treatment, TSG ameliorated serum levels of total cholesterol, triglyceride, and low density lipoprotein cholesterol, and increased serum levels of high density lipoprotein cholesterol in ApoE−/− mice. TSG suppressed hepatic steatosis, the formation of atherosclerotic lesions, and the formation of macrophage foam cells in ApoE−/− mice. Moreover, TSG improved the expressions of hepatic SR-BI, ABCG5, and CYP7A1, and up-regulated the protein expressions of aortic ABCA1 and ABCG1. An in-vitro study showed that TSG promoted macrophage cholesterol efflux and increased the protein expressions of ABCA1 and ABCG1. Our findings provide evidence for a positive role of TSG in preventing atherosclerosis by promoting reverse cholesterol transport. These effects may be achieved by stimulating cholesterol efflux through ABCA1 and ABCG1, promoting SR-BI-mediated cholesterol uptake in the liver, increasing secretion of cholesterol into bile by ABCG5, and improving cholesterol metabolism by the CYP7A1 pathway. In addition, antioxidative and anti-inflammatory effects of TSG may also contribute to its inhibitory effects on atherosclerosis. Further study is needed to investigate whether other potential mechanisms are involved in TSG-mediated atheroprotection.

scholarly journals The High Density Lipoprotein Cholesterol Hypothesis Revisited

2018 ◽  
Vol 10 (2) ◽  
pp. 84-103
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Reverse Cholesterol Transport ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
Epidemiological Studies ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Cholesterol Transport ◽  
Inverse Association

BACKGROUND: The strong inverse association of plasma levels of high-density lipoprotein cholesterol (HDL-C) with coronary heart disease (CHD) found in human epidemiological studies led to the development of the ‘HDL-C hypothesis’, which posits that intervention to raise HDL-C will result in reduced risk of CHD. However, recent evidence has raised doubts about the hypotheses that elevating HDL-C is necessarily therapeutic. Genetic variations that associate with altered HDL-C do not strongly associate with altered cardiovascular disease risk.CONTENT: HDL-mediated cholesterol efflux from macrophage foam cells or measurements of the flux of cholesterol from macrophages to the liver and feces seem to correlate better with atherosclerotic burden than with HDL-C levels. Thus, it may be time to modify the HDL-C hypothesis to the ‘HDL flux hypothesis’, where intervention to promote cholesterol efflux and reverse cholesterol transport will reduce CHD risk, regardless of whether it affects plasma HDL-C levels. A deeper understanding of the complex biology of HDL metabolism and its relationship to reverse cholesterol transport and atherothromobotic events is urgently needed. This might lead to biomarkers of HDL flux and functionality that are more informative than simple measurements of HDL-C levels.SUMMARY: It is now clear from recent clinical trial and genetic studies that some approaches to raising HDL-C levels may have no effect on CHD. This suggests the need to evaluate HDL-C-raising therapies in different clinical populations, as well as therapies targeted toward HDL flux and function rather than simply HDL-C elevation. Perhaps moving from a focus on the HDL-C hypothesis to a focus on the HDL flux hypothesis will permit a biologically based reassessment of the optimal therapeutic approach to targeting HDL for reduction in cardiovascular risk.KEYWORDS: reverse cholesterol transport, cholesterol efflux capacity, HDL dysfunction, HDL particle size, HDL lipidomics, HDL proteomics

Abstract P220: The Effect of Diet-Induced Weight Loss on HDL Functionality in Individuals with Metabolic Syndrome: Investigating Alteration of the Initial Step in Reverse Cholesterol Transport as a Function of Plasma Lipoprotein Composition

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Madhuri M Vasudevan ◽  
Urban Tchoua ◽  
Baiba Gillard ◽  
Hu Yu Lin ◽  
Peter Jones ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Weight Loss ◽  
Reverse Cholesterol Transport ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherogenic Dyslipidemia ◽  
Cholesterol Transport ◽  
Hdl Function ◽  
Macrophage Cholesterol Efflux

The prevalence of metabolic syndrome (MetS) with obesity-linked diabetes continues to increase globally and is associated with atherogenic dyslipidemia characterized by high triglycerides (TG), small, dense low-density lipoprotein cholesterol (LDL-C), and low high-density lipoprotein cholesterol (HDL-C) levels. HDL orchestrates the reverse cholesterol transport (RCT) process, initiated by macrophage cholesterol efflux (MCE). The traditional hypothesis is that individuals with dyslipidemia have impaired RCT that leads to atherogenesis. However, a recent study showed that one metric of HDL function, macrophage cholesterol efflux (MCE) to diluted patient plasma, inversely correlated with atherosclerotic burden, independent of plasma HDL-C levels. Moreover, cholesterol efflux from ABCA1-upregulated macrophage cell lines to sera of diabetic hypertriglyceridemic subjects is enhanced compared to normolipidemic (NL) controls. The effect of weight loss on MCE in obese individuals with MetS is unknown. The purpose of this study is to evaluate MCE in obese individuals with MetS as a function of plasma dyslipidemia, and to determine the effect of weight loss on the RCT process. We measured the rate of MCE from human monocytic leukemia THP1 cells to plasma of NL controls (n=24) and obese MetS (n=24) patients before and after 4 to 6 weeks of very low calorie, diet-induced weight loss. Weight loss in the MetS patients was significant, averaged 21.3 lbs, with concurrent significant decreases in TG, apoB, TC, LDL-C and non-HDL-C. Measures of insulin resistance, systolic blood pressure and kidney function improved with weight loss. HDL-C was not significantly altered, but apoA-I decreased with weight loss. MCE to plasma of obese MetS patients was higher than MCE to control plasma ((7.44 + 1.36) % vs (6.39 + 1.23) %, p=0.0069). MCE to plasma of obese MetS patients significantly decreased after weight loss (6.23 + 1.69) %, comparable to control values. MCE was strongly correlated to apoB levels (r 2 = 0.13 - 0.38), consistent with apoB lipoprotein function as a cholesterol sink. This was confirmed by size exclusion chromatography analysis of the distribution of effluxed cholesterol among plasma lipoproteins in 1 control and 2 Mets patients. In conclusion, obese patients with MetS demonstrate increased MCE, a measure of HDL function, compared to NL controls, which significantly decreases in response to diet-induced weight loss, concurrent with a reduction in triglyceride and apoB levels. These results suggest that the high apoB lipoprotein levels in MetS pateints facilitate MCE, and may at least partially compensate for the low HDL-C to promote RCT in these patients.

Abstract 631: Lipid Composition of Gold Nanoparticle-Templated High-Density Lipoprotein Analogs Dictates Cholesterol Efflux Function

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
R Kannan Mutharasan ◽  
Amritha T Singh ◽  
Kaylin M McMahon ◽  
C Shad Thaxton
Keyword(s):  
Fatty Acid ◽  
Lipid Content ◽  
Lipid Composition ◽  
Reverse Cholesterol Transport ◽  
Cholesterol Efflux ◽  
Lipid Membrane ◽  
Density Lipoprotein ◽  
High Density ◽  
High Density Lipoproteins ◽  
Cholesterol Transport

Background: Reverse cholesterol transport, the process by which cholesterol is effluxed from cells to high-density lipoproteins (HDL) and is delivered to the liver for clearance, is a promising pathway to augment for treatment of atherosclerosis. Though structure-function relationships for nascent, discoidal HDL and cholesterol efflux have been well studied, how the lipid composition of spherical HDL species - which varies in pathophysiological conditions - impacts their ability to mediate cholesterol efflux has not been investigated. Methods and Results: Spherical gold nanoparticles (5 nm) were used to synthesize spherical HDL analogs (HDL-NP) by adding ApoAI protein, and various lipids. With this strategy a panel of HDL-NP varying in lipid content was generated. HDL-NP designs tested include: dipalmitylphosphatidylcholine (DPPC, saturated fatty acid), dioleoylphosphatidylcholine (DOPC, unsaturated fatty acid), sphingomyelin, lysophosphatidylcholine (LPC), and mixtures thereof. All of these species are found in natural HDL. After characterizing protein and lipid stoichiometry of the purified HDL-NP, these HDL-NP designs were tested in the cellular reverse cholesterol transport assay using J774 mouse macrophages. These studies demonstrate that all HDL-NP designs mediate more efflux than equimolar amounts of ApoAI protein control, and further demonstrate that HDL-NP designs incorporating unsaturated phospholipid (DOPC), sphingomyelin, and LPC - each of which can increase disorder in the lipid membrane and thus give rise to opportunity for cholesterol to intercalate and bind - enhance cholesterol efflux compared to saturated phospholipid (DPPC) design. Conclusion: In summary, these results demonstrate that lipid content of HDL-NP - analogs of spherical HDL - dictates cholesterol efflux function, a finding which sheds light on the functional importance of lipid content variation seen in mature, spherical HDL species.

Abstract 257: Apolipoprotein M Is Not Present in Prebeta-1 HDL Particles

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Lita A Freeman ◽  
Robert Shamburek ◽  
Angel Aponte ◽  
Gregory J Kato ◽  
Alan T Remaley
Keyword(s):  
Retinoic Acid ◽  
Small Particle ◽  
Plasma Levels ◽  
Reverse Cholesterol Transport ◽  
Cholesterol Efflux ◽  
Cholesterol Transport ◽  
Apolipoprotein M ◽  
Sphingosine 1 Phosphate ◽  
2D Gel

BACKGROUND: Apolipoprotein M (apoM) is a 25 kD plasma protein present mainly in HDL. It has a hydrophobic pocket for carrying ligands variously reported as retinol, all- trans -retinoic acid, 9- cis -retinoic acid, sphingosine-1-phosphate (S1P) and oxidized phospholipids. In addition to mediating the effects of S1P and modulating oxidative stress, apoM has been reported to enhance cholesterol efflux and to increase plasma levels of small, preβ1 HDL, a particle that efficiently accepts cholesterol effluxed from cholesterol-loaded cells and plays a key role in reverse cholesterol transport. ApoM is present in α-migrating HDL particles but whether it is also present in small preβ1 HDL particles is disputed. Establishing the absence or presence of apoM in preβ1 HDL particles is essential for understanding its role in reverse cholesterol transport. METHODS: We performed native-native 2D gel electrophoresis on healthy volunteer plasma to separate native HDL particles by size and charge. Particles were blotted onto a membrane and probed with antibodies to apoM or apoA-I to identify specific HDL particles associated with apoM. Similar experiments were performed with plasma from patients with apoE-deficiency or from patients with low plasma levels of apoA-I and HDL. We also performed native 1D electrophoresis to visualize lipoprotein particles containing apoM. Finally, native-native 2D gels of purified HDL were used for proteomics of preβ1 particles. RESULTS: apoM was present in two large α-migrating HDL particles and in LDL-sized particles, as well as in one small particle that did not contain apoA-I. apoA-I but not apoE was required for formation of the large apoM-containing HDL particles. The small apoM particle was unaffected in apoA-I- and apoE-deficient patients. apoM was not present in preβ1 particles. CONCLUSION: apoM is not a stable component of small preβ1 apoA-I-containing HDL particles but instead resides mainly in two large HDL molecules and in LDL-sized particles, as well as a small particle that does not contain apoA-I. The role of apoM in cholesterol efflux requires further evaluation.

scholarly journals Cholesterol transport between red blood cells and lipoproteins contributes to cholesterol metabolism in blood

2020 ◽  
Vol 61 (12) ◽  
pp. 1577-1588
Author(s):  
Ryunosuke Ohkawa ◽  
Hann Low ◽  
Nigora Mukhamedova ◽  
Ying Fu ◽  
Shao-Jui Lai ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Cholesterol Efflux ◽  
Cholesterol Metabolism ◽  
Plasma Cholesterol ◽  
Translocator Protein ◽  
Plasma Lipoproteins ◽  
Cholesterol Transport ◽  
Autologous Plasma

Lipoproteins play a key role in transport of cholesterol to and from tissues. Recent studies have also demonstrated that red blood cells (RBCs), which carry large quantities of free cholesterol in their membrane, play an important role in reverse cholesterol transport. However, the exact role of RBCs in systemic cholesterol metabolism is poorly understood. RBCs were incubated with autologous plasma or isolated lipoproteins resulting in a significant net amount of cholesterol moved from RBCs to HDL, while cholesterol from LDL moved in the opposite direction. Furthermore, the bi-directional cholesterol transport between RBCs and plasma lipoproteins was saturable and temperature-, energy-, and time-dependent, consistent with an active process. We did not find LDLR, ABCG1, or scavenger receptor class B type 1 in RBCs but found a substantial amount of ABCA1 mRNA and protein. However, specific cholesterol efflux from RBCs to isolated apoA-I was negligible, and ABCA1 silencing with siRNA or inhibition with vanadate and Probucol did not inhibit the efflux to apoA-I, HDL, or plasma. Cholesterol efflux from and cholesterol uptake by RBCs from Abca1+/+ and Abca1−/− mice were similar, arguing against the role of ABCA1 in cholesterol flux between RBCs and lipoproteins. Bioinformatics analysis identified ABCA7, ABCG5, lipoprotein lipase, and mitochondrial translocator protein as possible candidates that may mediate the cholesterol flux. Together, these results suggest that RBCs actively participate in cholesterol transport in the blood, but the role of cholesterol transporters in RBCs remains uncertain.

Sign in / Sign up

Export Citation Format

Share Document