scholarly journals Hypocholesterolaemic effect of β β'-methyl-substituted hexadecanedioic acid (MEDICA 16) in the male hamster

1993 ◽  
Vol 289 (3) ◽  
pp. 911-917 ◽  
Author(s):  
N Mayorek ◽  
J Bar-Tana
Keyword(s):  
Cholesteryl Ester ◽  
Cholesterol Efflux ◽  
Free Cholesterol ◽  
Plasma Cholesterol ◽  
Cholesterol Acyltransferase ◽  
Cholesterol Content ◽  
Plasma Lipoproteins ◽  
Purina Chow ◽  
Apolipoprotein C ◽  
Bile Cholesterol

Treatment of cholesterol-fed male hamsters kept on a diet of purina chow with beta beta'-methyl-substituted hexadecanedioic acid (MEDICA 16) resulted in a progressive hypocholesterolaemic effect, amounting to a 50% decrease in the cholesterol content of all plasma lipoproteins. The decrease in plasma cholesterol could be accounted for by activation of plasma-cholesterol efflux through the liver into the bile mediated by MEDICA 16-induced (a) increase of the number of liver LDL receptors, (b) activation of liver neutral cholesteryl ester hydrolase with a concomitant inhibition of liver acyl-CoA cholesterol acyltransferase, resulting in shifting of the liver cholesteryl ester/free-cholesterol cycle in the direction of free cholesterol, and (c) activation of cholesterol efflux from the liver into the bile. The increase in bile cholesterol output was accompanied by an increase in bile phospholipids but not in bile acids. In contrast with rats, MEDICA 16-treatment of male hamsters did not result in a hypotriacylglycerolaemic effect, inhibition of lipogenesis, nor in a substantial decrease in plasma apolipoprotein C-III content.

Plasma cholesterol-raising potency of dietary free cholesterol versus cholesteryl ester and effect of β-sitosterol

2015 ◽  
Vol 169 ◽  
pp. 277-282 ◽  
Author(s):  
Yuwei Liu ◽  
Lin Lei ◽  
Xiaobo Wang ◽  
Ka Ying Ma ◽  
Yuk Man Li ◽  
...  
Keyword(s):  
Cholesteryl Ester ◽  
Free Cholesterol ◽  
Plasma Cholesterol

DEFIBROTIDE DECREASES CHOLESTEROL CONTENT IN HYPERCHOLESTEROLEMIC RABBIT AORTA, WITH NO MODIFICATION OF PLASMA OR LIPOPROTEIN CHOLESTEROL

1987 ◽  
Author(s):  
R Pescador ◽  
R Porta ◽  
R Niada ◽  
M Mantovani ◽  
G Prino
Keyword(s):  
Foam Cell ◽  
Plasma Cholesterol ◽  
Rabbit Aorta ◽  
Cholesterol Content ◽  
Normal Diet ◽  
Plasma Lipoproteins ◽  
Vascular Lesions ◽  
Aortic Tissue ◽  
Perfused Heart ◽  
Lipoprotein Lipids

Defibrotide was shown to stimulate the production of endogenous PGI2 from rat and hamster aortic tissue, as well as the production of PGi2 frcm the coronary vascular bed in the platelet perfused heart model. This effect was only seen in presence of platelets. Durirg the infusion period with Defibrotide thromboxane release remained unaffected while platelet cAMP rised. Defibrotide, was also able to reduce the secretion of ATP from platelets as well as to deaggregate platelet cluTps. It has been postulated that long-term administration of stable PGI^ metabolites or analogues could be a more useful means of enhancing cholesterol and cholesteryl ester mobilization out of the arterial “ foam” cell during early stages of cardiovascular disease. These observations prompted us to administer Defibrotide i.v. to cholesterol fed rabbits to verify if it could cause a decrease in cholesterol content of aortas. Aorta cholesterol was evaluated by gas chromatography. Plasma or lipoprotein lipids were assayed by enzymatic kits from Boehringer Biochemia. Plasma lipoproteins were separated by density gradient ultracentrifugation. Platelet aggregation was carried out with ADP using an optical aggregometer to find out the effective aggregatory concentration fifty (EC). Histology of the rabbit hearts was performed by optical microscopy on heart sections coloured with hematoxylin-eosine. Defibrotide caused a decrease (-49%, P < 0.05, vs. cholesterol fed rabbits treated with placebo) in cholesterol content of aortas with no modification of total plasma cholesterol, triglyceride and phospholipid. The cholesterol, triglyceride, phospholipid and protein of plasma lipoproteins were not affected too. The EC of rabbits treated with Defibrotide was 50 normalized (-9%, N.S. vs. control animals fed the normal diet and treated with placebo; cholesterol fed animals treated with placebo: -32%, P< 0.05 vs. control animals fed the normal diet). Vascular lesions in the hearts of animals treated with Defibrotide had a lower rate (33%) in comparison to that (87%) of animals fed with cholesterol and treated with placebo. It is concluded that the ability of Defibrotide to stimulate vascular PGI2 formation and to reduce platelet sensitivity could be helpful in reducing the amount of cholesterol in the cardiovascular system in atherosclerotic prone situations.

Cholesteryl Ester Transfer Protein Inhibitors

2016 ◽  
Vol 22 (2) ◽  
pp. 99-104 ◽  
Author(s):  
Julian Hardy McLain ◽  
Andrew Jacob Alsterda ◽  
Rohit R. Arora
Keyword(s):  
Cholesteryl Ester ◽  
Cholesteryl Ester Transfer Protein ◽  
Plasma Cholesterol ◽  
Genetic Research ◽  
Plasma Lipoproteins ◽  
Pharmacologic Therapy ◽  
Atherosclerotic Cardiovascular Disease ◽  
Current Standard ◽  
Transfer Protein ◽  
Cetp Inhibitors

The cholesteryl ester transfer protein (CETP) is a plasma protein that plays an important role in the transfer of lipids between plasma lipoproteins. The CETP inhibitors have been widely studied as a pharmacologic therapy to target plasma cholesterol in order to reduce the risk of atherosclerotic cardiovascular disease . Using CETP inhibitors as cholesterol modifiers was based on the genetic research that found correlations between CETP activity and cholesterol levels. Although CETP inhibitors are successful at altering targeted cholesterol markers, recent phase 3 outcome trials have shown limited benefit on cardiovascular outcomes when combined with the current standard of care. We discuss the science of CETP inhibition, compare the CETP inhibitors developed (torcetrapib, evacetrapib, dalcetrapib, and anacetrapib), the findings from the CETP inhibitor trials, and the future outlook for CETP inhibitors in cholesterol modification.

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.

Abstract 319: Design of Novel Chimeras to Provide Insight Into Structure/Function Activity of Apolipoprotein E3 and Apolipoprotein AI

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Mark Lek ◽  
Nnejiuwa Ibe ◽  
Wendy Beck ◽  
John K Bielicki ◽  
Paul M Weers ◽  
...  
Keyword(s):  
Rate Constant ◽  
Cholesterol Efflux ◽  
Plasma Cholesterol ◽  
Dominant Role ◽  
Density Lipoprotein ◽  
Lipid Binding ◽  
Plasma Lipoproteins ◽  
Peripheral Tissues ◽  
Terminal Domain ◽  
Cholesterol Levels

Apolipoprotein (apo) E3 and apoAI are exchangeable apolipoproteins that play a dominant role in regulating plasma cholesterol levels and are considered anti-atherogenic. ApoE3 (299 residues, ~34 kDa) serves as a ligand for the low density lipoprotein receptor (LDLr) family of proteins that mediate cellular uptake and clearance of plasma lipoproteins. The ability of apoE3 to function as a ligand for LDLr resides in the N-terminal domain (NT) of apoE3. ApoAI (243 residues, ~28 kDa) lowers cholesterol levels through its ability to promote cholesterol efflux from peripheral tissues such as macrophages, forming HDL, which transports cholesterol back to the liver. Residues located in the C-terminal domain (CT) of apoAI mediate this function of promoting cholesterol efflux. The objective of this study is to generate chimeric apolipoproteins composed of apoE3 and apoAI to better understand the role of the C-terminal tail of the parent proteins. Two chimeras were generated by “domain swapping”: apoE3-NT/apoAI-CT and apoAI-NT/apoE-CT. They were overexpressed in E. coli, isolated and purified. Western blot analysis revealed the presence of epitopes from both parent proteins. Circular dichroism spectroscopy revealed that the α-helical content of apoE3-NT/apoAI-CT and apoAI-NT/E-CT was 43 and 54 %, respectively, which is comparable to that of the parent proteins. Chemical denaturation was used to probe for changes in protein stability. Addition of CT of apoE3 to NT of apoAI conferred more stability to apoAI, while addition of CT of apoAI to NT of apoE3 had no significant effect on apoE3. The rate of apolipoprotein-induced conversion of DMPC vesicles to discoidal structures was followed to assess their lipid binding capability. ApoE3-NT/AI-CT displayed a rate constant that was ~10x higher compared to apoE3, while apoAI-NT/apoE-CT showed a rate constant similar to that of apoAI. Whereas apoE3-NT/apoAI-CT elicits the ability to bind to the LDLr, apoAI-NT/apoE-CT did not. Lastly, both chimeras promote ABCA1-mediated cholesterol efflux from J774 macrophages, with the efflux capability being 2-fold greater for apoAI-NT/apoE-CT. These results show that CT of apoAI can promote lipid binding of apoE3, while CT of apoE3 can improve cholesterol efflux ability of apoAI.

EFFECT OF LUTEINIZING HORMONE ANTISERUM ON PROGESTERONE AND 20α-DIHYDROPROGESTERONE SECRETION IN THE PREGNANT RAT

1972 ◽  
Vol 52 (3) ◽  
pp. 413-418 ◽  
Author(s):  
N. R. MOUDGAL ◽  
H. R. BEHRMAN ◽  
R. O. GREEP
Keyword(s):  
Luteinizing Hormone ◽  
Cholesteryl Ester ◽  
Corpus Luteum ◽  
Free Cholesterol ◽  
Single Injection ◽  
Cholesterol Content ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Progesterone Secretion ◽  
Cholesteryl Ester Content

SUMMARY The effect of a single injection of luteinizing hormone (LH) antiserum on ovarian progesterone and 20α-dihydroprogesterone in day-8 and day-15 pregnant rats was studied. Within 24 h of an injection of LH antiserum, progesterone secretion was reduced by 80% in day-8 and by 25% in day-15 pregnant rats. The 20α-dihydroprogesterone levels after antiserum treatment were markedly increased in rats which were 8 days pregnant but reduced in rats which were 15 days pregnant. The free cholesterol content of the ovary did not change after antiserum injection but the cholesteryl ester content markedly increased. It is thus apparent that neutralization of endogenous LH resulted in a significant reduction in the progesterone secretion of the corpus luteum of the pregnant rat. The significance of these results is discussed.

Apolipoprotein E Expression in Y1 Adrenal Cells Is Associated with Increased Intracellular Cholesterol Content and Reduced Free Cholesterol Efflux

Biochemistry ◽  
1994 ◽  
Vol 33 (17) ◽  
pp. 5049-5055 ◽  
Author(s):  
Margaret M. Prack ◽  
George H. Rothblat ◽  
Sandra K. Erickson ◽  
Mary E. Reyland ◽  
David L. Williams
Keyword(s):  
Apolipoprotein E ◽  
Cholesterol Efflux ◽  
Free Cholesterol ◽  
Cholesterol Content ◽  
Adrenal Cells ◽  
Intracellular Cholesterol

Generation of plasma free cholesterol from circulating lipoprotein-associated cholesteryl ester

1986 ◽  
Vol 250 (3) ◽  
pp. E265-E268
Author(s):  
I. J. Goldberg ◽  
R. S. Rosenfeld ◽  
I. Paul ◽  
B. Leeman
Keyword(s):  
Cholesteryl Ester ◽  
Free Cholesterol ◽  
Cholesterol Acyltransferase ◽  
High Density Lipoproteins ◽  
Protein Activity ◽  
Nitrobenzoic Acid ◽  
Transfer Protein ◽  
Lecithin Cholesterol Acyltransferase ◽  
Plasma Cholesteryl Ester ◽  
Monkey Plasma

Studies were performed to investigate the contribution of lipoprotein-associated cholesteryl ester (CE) in the monkey to circulating free cholesterol (FC). Monkey plasma was incubated with [14C]- or [3H]cholesteryl ester, and radiolabeled low-density lipoproteins (LDL) and high-density lipoproteins (HDL) were isolated by ultracentrifugation. Animals received labeled LDL or HDL. A rapid transfer of CE between lipoproteins was observed, consistent with an active CE transfer protein activity in the monkey. Within 4 h the percent of plasma radioactivity in FC after injection of CE-labeled LDL or HDL was, respectively, 30 and 7% of that of the ester. To determine whether the generation of FC was due to a circulating plasma cholesteryl ester hydrolase, monkey plasma was incubated with CE-labeled lipoproteins with and without 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). A small amount of FC (less than 3% of the radioactivity) was generated during this incubation but most of the FC production was inhibited by DTNB. Although a small amount of FC can be produced by a plasma cholesteryl esterase (perhaps via reverse action of lecithin-cholesterol acyltransferase), most of the FC in plasma derived from lipoprotein-associated CE is probably due to tissue uptake of lipoproteins and subsequent intracellular hydrolysis of the CE to produce FC.

Hypercholesterolaemia, hypotriacylglycerolaemia and increased lipoprotein lipase activity following orchidectomy in rats

1986 ◽  
Vol 113 (1) ◽  
pp. 133-139 ◽  
Author(s):  
Anna Haug ◽  
Arne T. Høstmark ◽  
Øystein Spydevold ◽  
Einar Eilertsen
Keyword(s):  
Lipoprotein Lipase ◽  
Hepatic Lipase ◽  
Plasma Cholesterol ◽  
Cholesterol Acyltransferase ◽  
Plasma Lipoproteins ◽  
Cholesterol Concentration ◽  
Hepatic Cholesterol ◽  
Faecal Excretion ◽  
Testosterone Substitution ◽  
Cholesterol Excretion

Abstract. Plasma lipoproteins, faecal cholesterol excretion, and activities of lecithin: cholesterol acyltransferase (LCAT) hepatic lipase (HL), and lipoprotein lipase (LPL) were determined in castrated rats, in rats treated with testosterone propionate after castration, and in sham-operated controls. Compared to control rats, whole-plasma total cholesterol (TC) rose, and triacylglycerols (TG) fell in castrated rats, but were normalized by androgen substitution. VLDL components tended to be reduced, whereas HDL2 components rose following castration. In general, testosterone substitution normalized the alterations induced by castration. Adipose tissue LPL was higher in castrated rats than in control rats, whereas activities of HL and LCAT were not significantly affected by the treatments. Hepatic cholesterol concentration, and faecal excretion of cholesterol and bile acids were not significantly altered by the treatments. Considering all 3 groups together, there was a significant positive correlation between the concentration of plasma cholesterol and cholesterol in liver, between plasma HDL2-cholesteryl esters and hepatic cholesterol, and also between HL and faecal cholesterol excretion. The results suggest that short term castration of rats causes increased levels of lipoprotein lipase and thereby brings about a lowering of VLDL and an increased concentration of LDL and HDL2. These effects are reflected in hypotriacylglycerolaemia and hypercholesterolaemia.

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