scholarly journals Atherogenic Impact of Lecithin-Cholesterol Acyltransferase and Its Relation to Cholesterol Esterification Rate in HDL (FERHDL) and AIP [log(TG/HDL-C)] Biomarkers: The Butterfly Effect?

2017 ◽  
pp. 193-203 ◽  
Author(s):  
M. DOBIÁŠOVÁ
Keyword(s):  
Free Cholesterol ◽  
Cholesterol Acyltransferase ◽  
Phospholipid Bilayer ◽  
Cholesterol Esterification ◽  
Final Decision ◽  
Cholesteryl Esters ◽  
Futile Cycle ◽  
Esterification Rate ◽  
Butterfly Effect ◽  
Moderate Change

The atherogenic impact and functional capacity of LCAT was studied and discussed over a half century. This review aims to clarify the key points that may affect the final decision on whether LCAT is an anti-atherogenic or atherogenic factor. There are three main processes involving the efflux of free cholesterol from peripheral cells, LCAT action in intravascular pool where cholesterol esterification rate is under the control of HDL, LDL and VLDL subpopulations, and finally the destination of newly produced cholesteryl esters either to the catabolism in liver or to a futile cycle with apoB lipoproteins. The functionality of LCAT substantially depends on its mass together with the composition of the phospholipid bilayer as well as the saturation and the length of fatty acyls and other effectors about which we know yet nothing. Over the years, LCAT puzzle has been significantly supplemented but yet not so satisfactory as to enable how to manipulate LCAT in order to prevent cardiometabolic events. It reminds the butterfly effect when only a moderate change in the process of transformation free cholesterol to cholesteryl esters may cause a crucial turn in the intended target. On the other hand, two biomarkers – FERHDL (fractional esterification rate in HDL) and AIP [log(TG/HDL-C)] can offer a benefit to identify the risk of cardiovascular disease (CVD). They both reflect the rate of cholesterol esterification by LCAT and the composition of lipoprotein subpopulations that controls this rate. In clinical practice, AIP can be calculated from the routine lipid profile with help of AIP calculator www.biomed.cas.cz/fgu/aip/calculator.php.

In vitro cholesterol esterification in human serum.

1977 ◽  
Vol 23 (3) ◽  
pp. 447-453 ◽  
Author(s):  
J K Yao ◽  
P J Dyck
Keyword(s):  
Free Cholesterol ◽  
Normal Subjects ◽  
Cholesterol Esterification ◽  
Tween 20 ◽  
Fractional Rate ◽  
Significant Difference ◽  
Reproducible Method ◽  
Esterification Rate ◽  
The Mean

Abstract We report a simple, convenient, and reproducible method, involving the use of radiolabeled cholesterol dispersed in Tween 20 as a tracer and endogenous lipoproteins as a substrate, for measuring the rate of serum cholesterol esterification in vitro. The reaction of lecithin acyltransferase (EC 2.3.1.43) was enhanced by the presence of Tween 20, which probably accelerates the exchange between radiolabeled cholesterol and endogenous lipoprotein cholesterol. In sera from 65 normal subjects, the in vitro cholesterol esterification rate was significantly correlated (r=0.47,P=0.001) with age. The mean rate of esterification of 31 subjects 30 years old or younger was significantly lower than that of 34 subjects 31 to 64 years of age. We found no significant difference in the rate of esterification between men and women. The rate of cholesterol esterification (nmol/ml per h) was significantly correlated with the concentration of endogenous free cholesterol in serum, but the fractional rate (the percentage of radiolabeled cholesterol esterified per hour) was inversely proportional to the endogenous free cholesterol. The fatty acid composition of the cholesteryl esters formed by the acyltransferase reaction may provide an index in recognizing some specific disorder.

Abstract 365: Increased Plasma Cholesterol Esterification by Lecithin-Cholesterol Acyltransferase Prevents Dysfunction of Red Blood Cells and Platelets and Protects from Development of Diet-Induced Atherosclerosis

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Seth G Thacker ◽  
Xavier Rousset ◽  
Boris L Vaisman ◽  
Marcelo J Amar ◽  
Lita A Freeman ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Aortic Root ◽  
Blood Cells ◽  
Free Cholesterol ◽  
Cholesterol Acyltransferase ◽  
Western Diet ◽  
Cholesterol Esterification ◽  
Face Analysis ◽  
Lecithin Cholesterol Acyltransferase ◽  
En Face

Introduction Free cholesterol plays a vital role in maintaining cell membrane fluidity and function. Elevated levels of cholesterol in red blood cells (RBC) and platelets have been demonstrated to impair the function of these cells. In circulation, free cholesterol freely exchanges between cells and lipoproteins and lecithin-cholesterol acyltransferase (LCAT) plays a role in this exchange. The esterification of cholesterol by LCAT sequesters it in the interior of lipoprotein particles and thereby limits its movement between lipoproteins and cells. Previously, SR-B1 KO mice have been shown to have dysfunctional RBCs and platelets and this dysfunction is exacerbated by a high fat diet. These mice have a partial defect in cholesterol esterification and are susceptible to diet induced atherosclerosis. Hypothesis We assessed in SR-BI KO mice whether increased cholesterol esterification by LCAT would improve numbers of RBCs and platelets, as well as prevent the development of atherosclerosis. Methods and Results Control (C57BL/6), SR-B1 KO, SR-B1 KO x LCAT KO(DKO), and SR-B1 KO x LCAT-Trg(LCAT-Trg) mice were maintained on a western diet for 7 months. As previously observed, SR-B1 KO mice had decrease numbers of RBCs and platelets compared to control mice, and over expression of LCAT restored levels to that of wild type mice, while loss of LCAT further abrogated the decrease in cell counts(n=10). Unexpectedly, LCAT-Trg mice has the highest levels of cholesterol in plasma, but RBC and platelets showed the lowest levels of free cholesterol, as assessed by filipin staining. Atherosclerosis in western diet fed mice was assessed by Oil Red O in two ways by looking at the aortic root(n=4) and by en face analysis of the aorta(n=10). In the aortic root SRB-1KO and DKO mice showed 3x the amount of lesion size as controls, while LCAT-Trg mice had levels comparable to the controls mice. The en face analysis also showed that DKO mice had 3x the amount of lesions, while LCAT-Trg and SRB-1KO mice had levels comparable to control mice. Conclusion LCAT is able to modulate the movement of cholesterol between circulating cells and lipoproteins thereby protecting RBCs and platelets. Our results further demonstrate a possible benefit of LCAT on the progression of atherosclerosis.

scholarly journals Morphological characterization of the cholesteryl ester cycle in cultured mouse macrophage foam cells.

1983 ◽  
Vol 97 (4) ◽  
pp. 1156-1168 ◽  
Author(s):  
D J McGookey ◽  
R G Anderson
Keyword(s):  
Cholesteryl Ester ◽  
Lipase Activity ◽  
Lipid Droplets ◽  
Free Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
The Body ◽  
Cyclic Process ◽  
Low Density ◽  
Cholesteryl Esters

Mouse peritoneal macrophages can be induced to accumulate cholesteryl esters by incubating them in the presence of acetylated low density lipoprotein. The cholesteryl esters are sequestered in neutral lipid droplets that remain in the cell even when the acetylated low density lipoprotein is removed from the culture media. Previous biochemical studies have determined that the cholesterol component of cholesteryl ester droplets constantly turns over with a half time of 24 h by a cyclic process of de-esterification and re-esterification. We have used morphologic techniques to determine the spatial relationship of cholesteryl ester, free cholesterol, and lipase activity during normal turnover and when turnover is disrupted. Lipid droplets were surrounded by numerous 7.5-10.0-nm filaments; moreover, at focal sites on the margin of each droplet there were whorles of concentrically arranged membrane that penetrated the matrix. Histochemically detectable lipase activity was associated with these stacks of membrane. Using filipin as a light and electron microscopic probe for free cholesterol, we determined that a pool of free cholesterol was associated with each lipid droplet. Following incubation in the presence of the exogenous cholesterol acceptor, high density lipoprotein, the cholesteryl ester droplets disappeared and were replaced with lipid droplets of a different lipid composition. Inhibition of cholesterol esterification caused cholesteryl ester droplets to disappear and free cholesterol to accumulate in numerous myelin-like structures in the body of the cell.

Effect of Ajuga iva on enzymes involved in the metabolism of cholesterol, in rat fed a cholesterol-enriched diet

2019 ◽  
Vol 50 (2) ◽  
pp. 303-313
Author(s):  
Sherazede Bouderbala ◽  
Malika Bouchenak
Keyword(s):  
Design Methodology ◽  
Cholesterol Metabolism ◽  
Cholesterol Acyltransferase ◽  
Cholesteryl Esters ◽  
Unesterified Cholesterol ◽  
Acyltransferase Activity ◽  
Content Type ◽  
Lecithin Cholesterol Acyltransferase ◽  
Male Wistar Rats ◽  
Adaptation Phase

Purpose This study aims to investigate the effect of Ajuga iva (Ai) on enzymes involved in the metabolism of cholesterol, in rat fed a cholesterol-enriched diet. Design/methodology/approach Male Wistar rats (n = 12), weighing 120 ± 5 g were fed on 1 per cent cholesterol-enriched diet [hypercholesterolemic (HC)] for 15 days (d15). After this adaptation phase, HC rats (total cholesterol = 6.5 ± 0.6 mmol/L) were divided into two groups fed the same diet and treated (Ai-HC) or not with (HC) with Ai for d15. Findings At day 15, in Ai-HC group compared to HC, serum triacylglycerol (TG) values were 1.4-fold lower (p = 0.002), whereas unesterified cholesterol (UC) contents were 1.8-fold higher (p = 0.0001). Serum phospholipids (PL) and cholesteryl esters (CE) contents and liver TG, UC, PL and CE values were not sensitive to Ai. TC/HDL-C and LDL-HDL1-C/HDL-C ratios were, respectively, 1.8- and 4-fold lower (p = 0.006 and p = 0.04). HDL2-C and HDL3-C amounts were enhanced by 40 and 74 per cent, respectively (p = 0.003 and p = 0.0001). HDL3-UC was 1.6-fold higher (p = 0.006); whereas PL contents were 1.4-fold lower (p = 0.003). HDL3-apo and HDL2-CE contents were similar between groups. A decreased of hydroxy-methyl-glutaryl-coenzyme A reductase and cholesterol 7α-hydroxylase activities (−44 and −25 per cent; p = 0.003 and p = 0.02, respectively) were noted. Lecithin: cholesterol acyltransferase activity was 1.5-fold higher (p = 0.001). Originality/value In HC rat, Ai is able to induce hypotriglyceridemia. However, it turns out that Ai may reduce cardiovascular risk by decreasing the reports of atherogenicity and modifying the activities of enzymes involved in the cholesterol metabolism.

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