scholarly journals Application of simultaneous spleen and liver perfusion to the study of reverse cholesterol transport

1994 ◽  
Vol 302 (1) ◽  
pp. 207-213 ◽  
Author(s):  
M A Mindham ◽  
P A Mayes
Keyword(s):  
Cholesteryl Ester ◽  
Reverse Cholesterol Transport ◽  
Liver Perfusion ◽  
Density Lipoprotein ◽  
Cholesterol Transport ◽  
Serum Lipoproteins ◽  
Unesterified Cholesterol ◽  
Net Uptake ◽  
High Haematocrit

1. A new method to isolate and perfuse the rat spleen and liver simultaneously with a common blood perfusate at high haematocrit was developed. The spleen was pre-labelled with [3H]cholesterol, enabling reverse cholesterol transport from an extrahepatic tissue to the blood and thence to the liver and bile to be studied in a single preparation in vitro. 2. The presence of the liver significantly increased the release of [3H]cholesterol from the spleen by 15%, compared with experiments where the spleen was perfused alone. 3. There was a substantial release of [3H]cholesterol and cholesterol mass from the spleen to serum lipoproteins, the majority (80%) to high-density lipoprotein (HDL), in which cholesteryl ester accumulated. 4. The HDL subfractions HDL2 and HDL3 (d 1.085-1.250) were most important for removal of cholesterol from the spleen, whereas HDL1 and HDL2 (d 1.050-1.125) were important for delivery of cholesterol to the liver, a net uptake of cholesteryl ester occurring only from these fractions. 5. Approximately half of the [3H]cholesterol released by the spleen was recovered in erythrocytes. Also, in experiments utilizing a lipoprotein-free perfusate containing erythrocytes, a substantial quantity of [3H]cholesterol was transported and/or exchanged into the liver and bile, indicating that erythrocytes play an important role in the equilibration of unesterified cholesterol between the tissues.

scholarly journals Reverse cholesterol transport in the rat. Studies using the isolated perfused spleen in conjunction with the perfused liver

1991 ◽  
Vol 279 (2) ◽  
pp. 503-508 ◽  
Author(s):  
M A Mindham ◽  
P A Mayes
Keyword(s):  
Reverse Cholesterol Transport ◽  
Liver Perfusion ◽  
Density Lipoprotein ◽  
Cholesterol Transport ◽  
Perfused Liver ◽  
Unesterified Cholesterol ◽  
Rapid Exchange ◽  
Net Release ◽  
Complete Process

1. A new method combining the use of an isolated perfused extrahepatic tissue with a perfused liver was developed as a model system for the study of reverse cholesterol transport. Rat spleens, initially labelled in vivo with [3H]cholesterol, were perfused for 3 h with whole blood. The spleen was then replaced with an isolated rat liver, whose uptake of cholesterol from the spleen-derived blood and excretion of cholesterol into bile constituents were determined. 2. During spleen perfusion, a net release of cholesterol mass and radioactivity to lipoproteins was observed. 3. During liver perfusion, there was also a rapid exchange or transport of unesterified cholesterol between high-density lipoprotein (HDL) and the liver, in particular with HDL2 (d = 1.085-1.125). 4. The liver showed an increased uptake of cholesteryl ester from serum that had previously been used in spleen perfusion. 5. Approximately half of the [3H]cholesterol released by the spleen was recovered in erythrocytes. During subsequent liver perfusion there was a substantial uptake of radioactivity from the erythrocytes, although less than that recorded from serum lipoproteins. 6. In all experiments there was significant excretion of [3H]cholesterol into bile; most (85%) was in bile acids. Thus the complete process of reverse cholesterol transport is observed in this dual-perfusion system.

scholarly journals Forhidrol, a bioactive fraction of Phaleria macrocarpa (Scheff.) Boerl., increases reverse cholesterol transport pathway by down-regulation of cholesteryl ester transfer protein activity

2018 ◽  
Vol 91 (1) ◽  
Author(s):  
Guntur Berlian ◽  
Olivia M. Tandrasasmita ◽  
Dwi A.S. Suciptan ◽  
Raymond R. Tjandrawinata
Keyword(s):  
Cholesteryl Ester ◽  
Cholesteryl Ester Transfer Protein ◽  
Reverse Cholesterol Transport ◽  
Density Lipoprotein ◽  
Cholesterol Transport ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Transfer Protein ◽  
Phaleria Macrocarpa ◽  
Bioactive Fraction

Phaleria macrocarpa (Scheff.) Boerl. is one of the most popular medicinal plants in Indonesia. This plant has traditionally been used to lower cholesterol and control hypertension. This study was performed to examine the effect of Forhidrol, a bioactive fraction of P. macrocarpa (Scheff.) Boerl., to increase reverse cholesterol transport through the down-regulation of cholesteryl ester transfer protein (CETP) activity in hepatocellular carcinoma cell lines. Measurement of target genes including liver X receptor (LXR), sterol regulatory element-binding protein 1 (SREBP1), scavenger receptor class B type 1, low-density lipoprotein (LDL) receptor, apolipoprotein B, CYP11B1, CYP11B2, peroxisome proliferatoractivated receptor α (PPARα), peroxisome proliferator-activated receptor δ (PPARδ) and peroxisome proliferator-activated receptor γ (PPARγ) were done using realtime polymerase chain reaction assay. Secreted CETP and apolipoprotein A-1 were analyzed using western blot. CETP activity in vitro was measured using CETP inhibitor drug screening kit and triglyceride synthesis was measured using enzyme-linked immunosorbent assay. Forhidrol was found to significantly down-regulate CETP mRNA expression, as well as total CETP and cholesteryl esters transfer activity (P<0.05). It specifically reduced transcriptional level of regulatory genes of CETP promoter including SREBP-1 and LXR. Forhidrol also significantly increased PPARδ and PPARα expression (P<0.05) and slightly repressed triglycerides synthesis. In vivo study showed elevated high-density lipoprotein (HDL) levels in rabbits after 4-week treatment of Forhidrol at a dose of 37.5 mg/1.5 kg body weight compared to placebo. Conversely, LDL, triglyceride and CETP activity were decreased. Forhidrol increased HDL levels by reducing CETP-dependent transfer of cholesterol from HDL to LDL particles. Looking at possible side effects, Forhidrol apparently acted as a safe agent without negative effect towards blood pressure. These findings suggested that Forhidrol may be further developed as a potential anti-atherogenic drug.

scholarly journals Reduced Reverse Cholesterol Transport Efficacy in Healthy Men with Undesirable Postprandial Triglyceride Response

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 810 ◽  
Author(s):  
Alexandre Motte ◽  
Julie Gall ◽  
Joe-Elie Salem ◽  
Eric Dasque ◽  
Martine Lebot ◽  
...  
Keyword(s):  
Cholesteryl Ester ◽  
Reverse Cholesterol Transport ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
Cholesterol Transport ◽  
Human Macrophages ◽  
Increased Risk ◽  
Postprandial Triglyceride ◽  
Triglyceride Rich Lipoprotein ◽  
The Impact

Elevation of nonfasting triglyceride (TG) levels above 1.8 g/L (2 mmol/L) is associated with increased risk of cardiovascular diseases. Exacerbated postprandial hypertriglyceridemia (PP–HTG) and metabolic context both modulate the overall efficacy of the reverse cholesterol transport (RCT) pathway, but the specific contribution of exaggerated PP–HTG on RCT efficacy remains indeterminate. Healthy male volunteers (n = 78) exhibiting no clinical features of metabolic disorders underwent a postprandial exploration following consumption of a typical Western meal providing 1200 kcal. Subjects were stratified according to maximal nonfasting TG levels reached after ingestion of the test meal into subjects with a desirable PP–TG response (GLow, TG < 1.8 g/L, n = 47) and subjects with an undesirable PP–TG response (GHigh, TG > 1.8 g/L, n = 31). The impact of the degree of PP–TG response on major steps of RCT pathway, including cholesterol efflux from human macrophages, cholesteryl ester transfer protein (CETP) activity, and hepatic high-density lipoprotein (HDL)-cholesteryl ester (CE) selective uptake, was evaluated. Cholesterol efflux from human macrophages was not significantly affected by the degree of the PP–TG response. Postprandial increase in CETP-mediated CE transfer from HDL to triglyceride-rich lipoprotein particles, and more specifically to chylomicrons, was enhanced in GHigh vs. GLow. The hepatic HDL-CE delivery was reduced in subjects from GHigh in comparison with those from GLow. Undesirable PP–TG response induces an overall reduction in RCT efficacy that contributes to the onset elevation of both fasting and nonfasting TG levels and to the development of cardiometabolic diseases.

scholarly journals HDL Is Not Dead Yet

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 128
Author(s):  
Shuhui Wang Lorkowski ◽  
Jonathan D. Smith
Keyword(s):  
Reverse Cholesterol Transport ◽  
Mendelian Randomization ◽  
Density Lipoprotein ◽  
Epidemiological Studies ◽  
Structure And Function ◽  
In Vitro Assays ◽  
Cholesterol Transport ◽  
Rare Mutations ◽  
And Function

High-density lipoprotein cholesterol (HDL-C) levels are inversely correlated with coronary heart disease (CHD) in multiple epidemiological studies, but whether HDL is causal or merely associated with CHD is unclear. Recent trials for HDL-raising drugs were either not effective in reducing CHD events or, if beneficial in reducing CHD events, were not conclusive as the findings could be attributed to the drugs’ LDL-reducing activity. Furthermore, the first large Mendelian randomization study did not causally relate HDL-C levels to decreased CHD. Thus, the hypothesis that HDL is protective against CHD has been rightfully challenged. However, subsequent Mendelian randomization studies found HDL characteristics that are causally related to decreased CHD. Many aspects of HDL structure and function, especially in reverse cholesterol transport, may be better indicators of HDL’s protective activity than simply measuring HDL-C. Cholesterol efflux capacity is associated with lower levels of prevalent and incident CHD, even after adjustment for HDL-C and apolipoprotein A-1 levels. Also, subjects with very high levels of HDL-C, including those with rare mutations that disrupt hepatic HDL uptake and reverse cholesterol transport, may be at higher risk for CHD than those with moderate levels. We describe here several cell-based and cell-free in vitro assays of HDL structure and function that may be used in clinical studies to determine which of HDL’s functions are best associated with protection against CHD. We conclude that the HDL hypothesis may need revision based on studies of HDL structure and function, but that the HDL hypothesis is not dead yet.

Smoking prevents the intravascular remodeling of high-density lipoprotein particles: implications for reverse cholesterol transport

Metabolism ◽  
2004 ◽  
Vol 53 (7) ◽  
pp. 858-862 ◽  
Author(s):  
Águeda C.M Zaratin ◽  
Eder C.R Quintão ◽  
Andrei C Sposito ◽  
Valéria S Nunes ◽  
Ana Maria Lottenberg ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Reverse Cholesterol Transport ◽  
Density Lipoprotein ◽  
High Density ◽  
Cholesterol Transport ◽  
Lipoprotein Particles

Rapid transformation of [3H]cholesteryl ester m rat high-density lipoprotein: in vivo and in vitro studies

Steroids ◽  
1990 ◽  
Vol 55 (7) ◽  
pp. 308-313
Author(s):  
I.J. Goldberg ◽  
R.S. Rosenfeld ◽  
I. Paul ◽  
L.K. Miller ◽  
M.L. Tiell
Keyword(s):  
High Density Lipoprotein ◽  
Cholesteryl Ester ◽  
Density Lipoprotein ◽  
High Density ◽  
In Vitro Studies ◽  
Rapid Transformation
Sign in / Sign up

Export Citation Format

Share Document