Influence of Murine Serum Amyloid a 2.1, and its Active Domains, on Human Macrophage Cholesterol Export in Cell Culture
Gilles Grateau, Robert A. Kyle, Martha Skinner in Amyloid and Amyloidosis, 2004
Experiments were also carried out to identify the domains in SAA2.1 that are responsible for enhancing CEH activity in J774 cells that had been pre-loaded and radio-labeled with cholesteryl esters (Figure 1B). This was performed using liposomes containing one of each of the four synthetic peptides of SAA2.1 noted above. These studies were done in the presence of Sandoz 58-035, an ACAT inhibitor, to prevent the re-esterification of liberated cholesterol and [14C]oleate. Incubations proceeded for various times as indicated, following which the remaining quantities of [14C]-labeled cholesteryl oleate in cells were measured to determine the rate of hydrolysis of cholesteryl ester. With re-esterification blocked, there were no significant differences in the rate of hydrolysis of [14C]-labeled cholesteryl oleate in cells cultured in the presence of protein free liposomes or liposomes at 0.5 |iM synthetic peptides corresponding to amino acid residues 1-20, 21-50 and 51-80 from the N-terminal of murine SAA2.1, respectively. However, an equivalent amount of liposomes containing the synthetic peptide corresponding to residues 74-103 of SAA2.1 caused a 3-fold increase in CEH activity.
The Stimulation of Steroid Biosynthesis by Luteinizing Hormone
Mario Ascoli in Luteinizing Hormone Action and Receptors, 2019
Free cholesterol is obtained from cholesteryl esters by the action of cholesteryl esterase. LH/hCG has been shown to increase the activity of this enzyme in the corpus luteum65,66 and in Leydig cells.67 Behrman and Armstrong65,66 have reported that the cytosolic fraction of the rat corpus luteum has the highest activity of this enzyme and that this enzyme can be stimulated by administration of LH. In a more recent study, Tuckey and Stevenson68 investigated the subcellular distribution of the cholesteryl esterase in ovaries from maturing and superovulated immature rats. In agreement with the earlier studies by Behrman and Armstrong, the highest activity of cholesteryl esterase was found in the cytosol. This was true at all stages of ovarian development. In general, more of the remaining esterase activity was found in micorosomal fractions than in mitochondria. A marked increase in cholesteryl esterase activity as well as endogenous cholesterol ester concentration was observed in rats between 29 and 42 days, when corpora lutea first developed. Similar results were obtained in 20-day-old rats treated with gonadotropins to cause superovulation. Upon acute hCG stimulation on day 6, superovulated rats increased the rate of steroid hormone production and activation of the mitcochondrial and microsomal cholesteryl esterase, but not the cytosolic enzyme.68 This latter finding is in disagreement with the earlier findings by Behrman and Armstrong, who observed hCG stimulation of the cytosol cholesteryl esterase in corpora lutea of superovulated rats.65,66
Atherosclerosis
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
HDL2 may be related to estrogens, since its amount in premenopausal women is about three times greater than in men. This lipid:protein ratio is about 1:1, and it contains 32% cholesterol, 10% triglycerides and 51% phospholipids. In the HDL2 component, lecithin constitutes 70 to 80% of the total sphingomyelin (12 to 14%). The predominant fatty acid in cholesteryl esters is linoleic acid. The concentration of HDL lecithin is influenced by risk factors, including coronary heart disease.567
An update on emerging drugs for the treatment of hypercholesterolemia
Published in Expert Opinion on Emerging Drugs, 2021
Adam J Nelson, Kristen Bubb, Stephen J Nicholls
Cholesteryl ester transfer protein (CETP) plays an important role in the regulation of lipid metabolism, promoting transfer of esterified cholesterol from HDL to VLDL and LDL particles, in exchange for triglycerides [62]. CETP inhibitors were originally developed on the basis of their ability to raise HDL cholesterol levels [62] and atheroprotective properties of CETP inhibition in rabbit models [63–66]. However, the clinical development of small molecule CETP inhibitors has proven challenging. The first agent, torcetrapib, was demonstrated to produce an increase cardiovascular events and all-cause mortality [67]. Subsequent analyses revealed that torcetrapib possessed a number of off-target toxicities, including elevation of blood pressure, adrenal synthesis of cortisol and aldosterone and aortic wall expression of endothelin [67–69]. The ability to demonstrate a lack of such effects would permit other CETP inhibitors to proceed in development. However, outcomes trials of the modest CETP inhibitor, dalcetrapib, and the potent CETP inhibitor, evacetrapib, demonstrated clinical futility with no impact on cardiovascular events [70,71]. Anacetrapib, an additional potent CETP inhibitor, was demonstrated to produce a significant reduction in cardiovascular events, with the degree of benefit directly proportional to the extent of lowering levels of atherogenic lipoproteins [72]. Clinical development of this agent was halted due to the finding of adipose tissue accumulation.
Platelet-lymphocyte ratio (PLR) and all-cause mortality in general population: insights from national health and nutrition education survey
Published in Platelets, 2019
Kanupriya Mathur, Nargiza Kurbanova, Rehan Qayyum
Platelet and lymphocyte counts were reported in 1000 cells/µL. PLR was calculated by dividing the platelet count by the lymphocyte count. The hazard ratio with 95% confidence intervals (CIs) were reported for difference from the lowest PLR quartile. Serum creatinine was measured using the Jaffe rate method (kinetic alkaline picrate) and glomerular filtration rate (GFR) was calculated using Chronic Kidney Disease Epidemiology Collaboration equation and was reported in ml/min/1.73 m2. Total cholesterol was measured enzymatically in serum or plasma in a series of coupled reactions that hydrolyze cholesteryl esters. Serum c-reactive protein (CRP) was quantified using latex-enhanced nephelometry. Serum glucose level was measured using the Beckman Synchron LX20 test (Beckman Coulter, Fullerton, CA, USA) on refrigerated specimens. Diabetes was defined as random glucose >200 mg/dL, HbA1c >7%, self-report of diabetes diagnosis, or taking diabetes medications.
Systematic Review and Meta-Analysis of the Prognostic Value of Serum High-Density Lipoprotein Cholesterol Levels for Solid Tumors
Published in Nutrition and Cancer, 2019
Bo Hao, Baochen Bi, Chen Sang, Miaomei Yu, Dongmei Di, Guanghua Luo, Xiaoying Zhang
Abnormal lipid and apolipoprotein metabolism resulting from high fat intake and physical inactivity has been associated with various kinds of cancer (2,3). High-density lipoprotein cholesterol (HDL-C) consists of various apolipoproteins, phospholipids, enzymes, fatty acids, cholesterol, and other functional proteins, and is highly heterogeneous in its structure, intravascular metabolism, and biological activity. Recently, HDL-C has gained much attention, as it not only functions in cardiovascular disease, but also is involved in tumorigenesis via its effects on cell cycle entry, mitogen-activated protein kinase-dependent signaling (4) and apoptotic regulation (5). HDL-C is mainly secreted by the liver and the small intestine (6); in fact, the liver secretes ∼70–80% of the total HDL-C in plasma. Apolipoprotein AI is the major structural protein providing the framework by which HDL-C can bear phospholipids and cholesterol (7). HDL-C is remodeled by various plasma proteins and is subsequently catabolized in the plasma by cell receptors and other proteins, including hepatic lipase (8), endothelial lipase (9), cholesteryl ester transfer protein (10), scavenger receptor BI (SR-BI) (11), etc. Hepatocytes and steroidogenic cells (such as enterocytes, macrophages, adipose cells, and testicular cells) can endocytose HDL-C particles via SR-B. Cholesteryl esters are then isolated from the HDL-C particles and hydrolyzed within cells (12). The remaining part of the HDL-C is re-secreted into the circulation, where it continues to carry peripheral cholesterol.
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