Cholesterol Journal Articles

Record 10421 to 10440

R192Q paraoxonase gene variant is associated with a change in HDL-cholesterol level during dietary caloric restriction in nondiabetic healthy males
Obata, T., T. Ito, et al. (2003), J Atheroscler Thromb 10(1): 57-62.
Abstract: Paraoxonase (PON), an HDL- associated enzyme, may protect against the development of atherosclerosis. Single nucleotide polymorphisms of PON have been reported to be associated with an incidence of coronary heart diseases. We investigated the effect of PON R192Q variants on serum lipid profile after caloric restriction in nondiabetic healthy males. After caloric restriction for 12 weeks, the levels of high-density lipoprotein cholesterol (HDL-C) increased in the subjects carrying RR genotype, but not in the QR and QQ genotypes. The changes in HDL-C from the baseline values in the RR genotype were significantly different from those in the QR and QQ genotypes. Although the changes in lipoprotein lipase activity were not different among three genotypes, we observed a significant difference in the changes in hepatic lipase (HL) activity after caloric restriction, namely, a decrease in the RR genotype and an increase in the subjects carrying the Q allele. In addition, the changes in fasting insulin levels significantly correlated with those in HDL-C levels in the RR genotype, not in the QR and QQ genotypes. PON R192Q polymorphism could affect HDL-C levels after caloric restriction presumably due to decreased HL activity and altered insulin resistance.

R219K polymorphism of the ABCA1 gene and its modulation of the variations in serum high-density lipoprotein cholesterol and triglycerides related to age and adiposity in white versus black young adults. The Bogalusa heart study
Srinivasan, S. R., S. Li, et al. (2003), Metabolism 52(7): 930-4.
Abstract: Mutations in adenosine triphosphate (ATP)-binding cassette transporter 1 (ABCA1) gene have been established as the molecular defect in Tangier disease and familial hypoalphalipoproteinemia, uncommon genetic disorders characterized by deficient or depressed high-density lipoprotein (HDL) cholesterol and increased triglycerides. However, information regarding the frequency of common variants, including Arg219Lys (R219K) within the coding region of the ABCA1 gene and their effect on these phenotypes in the general population is limited. This study examined the frequency and phenotypic effect of R219K variant in a community-based sample of 887 white and 390 black young adults aged 20 to 38 years. The frequency of the variant allele (K219) was higher in blacks than in whites (0.595 v 0.262, P<.001), with carriers (KK+RK) representing 83.8% of blacks versus 44.2% of whites. After adjusting for age, body mass index (BMI), and sex, the genotype effect on HDL cholesterol and natural logarithm of triglycerides was not apparent in whites or blacks. However, significant interaction effects of genotype and age on HDL cholesterol (P<.001) and genotype and BMI on triglycerides (P=.029) were found in whites. Carriers (KK+RK), unlike noncarriers (RR) showed a positive relationship between age and HDL cholesterol (regression coefficient beta=0.28, P=.029 for carriers v beta=-0.18, P=.112 for noncarriers). In addition, the variant allele attenuated the adverse positive relationship between BMI and triglycerides (beta=0.032, P<.001 for carriers v beta=0.046, P<.001 for noncarriers). These results indicate that the K219 allele frequency differs markedly between blacks and whites, and that the variant-allele modulates the association between age and HDL cholesterol, as well as body fatness and triglycerides in a beneficial manner only in whites.

Rab7 gene is up-regulated by cholesterol-rich diet in the liver and artery
Kim, J. Y., M. K. Jang, et al. (2002), Biochem Biophys Res Commun 293(1): 375-82.
Abstract: To identify genes responding to the cholesterol-rich diet, differentially expressed hepatic genes have been searched from a diet-induced hypercholesterolemic rabbit by differential display reverse transcription-polymerase chain reaction (DDRT-PCR). Among the many screened genes, Rab7 gene was shown to be distinctively up-regulated in response to the cholesterol-loading into the rabbit. To visualize the location of elevated Rab7 expression in tissues, patterns of the gene expression were monitored within hepatic and aortic tissues by in situ hybridization and immunohistochemistry. The expression of Rab7 was obviously increased in the hepatic tissues, especially in the endothelial cells and hepatocytes around central veins of the high cholesterol-fed rabbit, compared to the tissues from rabbit fed a normal diet. To find out a potential relationship between the Rab7 and the atherogenesis, the same experiments were conducted with the atherosclerotic plaques obtained from rabbit and human. The elevated expression of Rab7 gene was clearly evident in both tissues, suggesting that the Rab7 may be involved in the process of atherogenesis.

Rabbit and human liver contain a novel pentacyclic triterpene ester with acyl-CoA: cholesterol acyltransferase inhibitory activity
Tabas, I., L. L. Chen, et al. (1990), J Biol Chem 265(14): 8042-51.
Abstract: Acyl-coenzyme A (CoA):cholesterol acyltransferase (ACAT) catalyzes the intracellular fatty acid esterification of cholesterol and is thought to play a key role in lipoprotein metabolism and atherogenesis. Herein we describe the purification and characterization of a novel pentacyclic triterpene ester from rabbit liver that has ACAT inhibitory activity. The inhibitor was purified by a combination of silicic acid chromatography and preparative thin layer chromatography. The compound inhibited both rabbit and rat liver microsomal ACAT activity with an IC50 = 20 microM. The lipid did not inhibit fatty acid incorporation into triglycerides, diglycerides, monoglycerides, or phospholipids nor did it inhibit plasma lecithin:cholesterol acyltransferase activity. However, rat liver microsomal acyl-CoA:retinol acyltransferase activity was inhibited by the terpene ester. Kinetic data are consistent with a mechanism in which ACAT is inhibited by the compound in an irreversible manner. The subcellular fractionation pattern of both ACAT activity and the ACAT inhibitor were similar in rabbit liver (both were approximately equally distributed in membranes that pelleted at 10,000 X g and 100,000 X g). A lipid with similar properties to the rabbit liver inhibitor was found in many other rabbit tissues, including adrenal and spleen, as well as in human liver. Rat liver did not contain this lipid. Structural analysis by NMR, mass spectrometry, and x-ray crystallography indicated that the rabbit liver inhibitor was a fatty acid ester (mostly stearate) of a pentacyclic triterpene acid. The carbon skeleton of the triterpene moiety is a new member of the olean-12-ene triterpene family. Both the negatively charged carboxylic acid group of the triterpene moiety and the esterified fatty acid group were necessary for the ACAT-inhibitory activity of the triterpene ester. Lastly, we present preliminary data which, together with the structural homology of the rabbit triterpene with known plant compounds, suggest the hypothesis that the triterpene moiety of the rabbit ACAT inhibitor arises from dietary absorption of a plant triterpene.

Radiation-induced changes in the content of squalene, lathosterol and cholesterol in rat blood proteins
Palamarchuk, V. I., V. M. Klimashevskii, et al. (1991), Radiobiologiia 31(3): 427-31.
Abstract: Normal and irradiated fibrinogen, gamma-globulins, alpha- and beta-globulins and albumins of blood plasma were shown to contain squalene, lathosterol, cholesterol and some other compounds as lipid components. Radiation alteration of the total number of unsaponifiable substances and some lipid components in the individual blood plasma proteins followed certain regularities depending on the kind of a protein. The level of radiation changes in the content of lipid components in specific proteins of blood plasma was shown to be a function of radiation dose and time after irradiation.

Radical scavenging effect of gliclazide in diabetic rats fed with a high cholesterol diet
Onozato, M. L., A. Tojo, et al. (2004), Kidney Int 65(3): 951-60.
Abstract: BACKGROUND: Gliclazide is a sulphonylurea antidiabetic drug with anti-oxidant effect due to its azabicyclo-octyl ring. We hypothesized that gliclazide may have a beneficial effect on diabetic nephropathy via radical scavenging. METHODS: Streptozotocin-induced diabetic rats fed a 4% cholesterol diet high cholesterol-diabetes mellitus (HC-DM) (N= 12) were treated with gliclazide (HC-DM + gliclazide) (N= 12) or glibenclamide (HC-DM + glibenclamide) (N= 12) after 2 weeks of the diabetes induction, and normal rat fed with 4% cholesterol served as control high cholesterol-control (HC-control) (N= 12). Renal expression of endothelial nitric oxide synthase (eNOS) and intracellular adhesion molecule-1 (ICAM-1), oxidative stress production via nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase and antioxidant enzyme manganese superoxide dismutase (MnSOD) were evaluated at 4 weeks and renal damage was examined at 8 weeks. RESULTS: HC-DM showed significant increase in renal NAD(P)H oxidase and reduction in MnSOD with a significant increase in urinary lipid peroxidation products and H2O2 excretion compared to HC-control. Gliclazide treatment, but not glibenclamide, significantly reduced the oxidative products and NAD(P)H oxidase. There was no difference in renal eNOS expression between HC-DM and HC-control rats, and only gliclazide treatment enhanced eNOS expression. Renal damage evaluated by increased glomerular macrophage migration via enhanced ICAM-1 expression, mesangial matrix expansion, and albuminuria was significantly increased in HC-DM, and they were ameliorated by gliclazide but not by glibenclamide. CONCLUSION: Gliclazide reduced oxidative stress in diabetic rats fed a high cholesterol diet with reduction of renal NAD(P)H oxidase expression, enhanced MnSOD and eNOS expression, and had a beneficial effect on glomerular macrophage infiltration and mesangial expansion.

Radical therapy of refractory hyperlipidemia: extracorporeal cholesterol elimination
Kostner, K. M. (1994), Wien Med Wochenschr 144(12-13): 333-5.
Abstract: In Austria atherosclerosis related diseases are responsible for the death of more than 50% of the population. There is a linear relationship between lowering cholesterol and the mortality of coronary heart disease. Apart from diet and drug therapy for the treatment of hypercholesterolemia we nowadays have very potent extracorporeal cholesterol lowering therapies. In combination with HMG-CoA reductase inhibitors LDL-cholesterol can be lowered by 80% with these procedures. In particular homozygote familial hypercholesterolemia is an absolute indication for extracorporeal lipid lowering. Refractory heterozygote FH and secondary hypercholesterolemia in combination with other risk factors can also be controlled by extracorporeal cholesterol elimination. Since some of these extracorporeal therapies also improve the hemorheological situation they are also being used to treat peripheral vascular disease and cerebral atherosclerosis.

Radiographic osteoarthritis and serum cholesterol
Al-Arfaj, A. S. (2003), Saudi Med J 24(7): 745-7.
Abstract: OBJECTIVE: To find out the relationship between radiographic osteoarthritis (OA) of the knee, generalized OA and serum cholesterol. METHODS: Over a period of 7 months from September 1998 through to March 1999, 246 patients attending 14 primary care clinics in Northern Riyadh, Kingdom of Saudi Arabia, for different non-musculoskeletal complaints were recruited in the study. Their knees, hands and wrists were radiographed. Their ages, sex, weight, height, body mass index (BMI), fasting serum cholesterol, triglycerides and uric acid were recorded. RESULTS: There were 113 females and 133 males with average ages 46 14.2 and 51.54 16.0 years. One hundred and twenty-two (49.6%) cases of knee OA and 58 (23.6%) cases of generalized OA were found and analyzed for the association with serum cholesterol levels. Crude odds ratio (OR) for the relationship between knee OA and the third tertile of serum cholesterol was 2.33 (95% CI, 1.19-4.58) which on adjusting for age, sex, BMI, serum uric acid and triglycerides were 2.68 (95% CI, 2.00-3.64). For generalized OA, the crude odds ratio (OR) in relation to the third tertile of serum cholesterol was 1.65 (95% CI, 0.78-3.53), adjusted OR was 2.18 (95% CI, 1.55-3.15). CONCLUSION: The results showed an association between high serum cholesterol level and both knee and generalized OA.

Radiolabeled cholesterol as a reporter for assessing one-electron turnover of lipid hydroperoxides
Korytowski, W., M. Wrona, et al. (1999), Anal Biochem 270(1): 123-32.
Abstract: A novel approach for assessing the peroxidative chain initiation potency of lipid hydroperoxides has been developed, which involves use of 14C-labeled cholesterol (Ch) as a "reporter" lipid. Unilamellar liposomes containing 1-palmitoyl-2-oleoyl-phosphatidylcholine, 14CCh, and 3beta-hydroxy-5alpha-cholest-6-ene-5-hydroperoxide (5alpha-OOH) or 3beta-hydroxycholest-5-ene-7alpha-hydroperoxide (7alpha-OOH) 100:75:5, mol/mol were used as a test system. Liposomes incubated in the presence of ascorbate and a lipophilic iron complex were analyzed for radiolabeled oxidation products/intermediates (ChOX) by means of silica gel high-performance thin layer chromatography with phosphorimaging detection. The following ChOX were detected and quantified: 7alpha-OOH, 7beta-OOH, 7alpha-OH, 7beta-OH, and 5, 6-epoxide. Total ChOX yield increased in essentially the same time- and iron-dependent fashion for initiating 5alpha-OOH and 7alpha-OOH. The initial rate of 14C7alphabeta-OH formation was greatly diminished when GSH and ebselen (a selenoperoxidase mimetic) were present, consistent with the attenuation of one-electron peroxide turnover. 14CCh-labeled L1210 cells also accumulated ChOX when incubated with 5alpha-OOH-containing liposomes. The rate of accumulation was substantially greater for Se-deficient than Se-sufficient cells, indicating that peroxide-induced chain reactions were modulated by selenoperoxidase action. These results illustrate the advantages of the new approach for highly sensitive in situ monitoring of cellular peroxidative damage.

Raised HDL cholesterol in Fabry disease: response to enzyme replacement therapy
Cartwright, D. J., A. L. Cole, et al. (2004), J Inherit Metab Dis 27(6): 791-3.
Abstract: Fabry disease patients have increased risk of vascular disease despite cardioprotective increased HDL-cholesterol. Enzyme therapy does not significantly alter the lipid profile in the short term.

Raised plasma cholesterol precursors after ileal transportation in the pig
Pakarinen, M., T. A. Miettinen, et al. (1996), Transplant Proc 28(5): 2566-7.

Raising HDL cholesterol
Melnikova, I. (2005), Nat Rev Drug Discov 4(3): 185-6.

Raising HDL cholesterol with low-dose nicotinic acid and bezafibrate: preliminary experience
Luria, M. H. and D. Sapoznikov (1993), Postgrad Med J 69(810): 296-9.
Abstract: Nicotinic acid is an effective agent for elevating HDL cholesterol but is limited by side effects. In order to improve tolerance and lipid levels, we combined low-dose nicotinic acid with bezafibrate. We gave low-dose (mean 435 mg/day) nicotinic acid to 37 patients with low HDL cholesterol, bezafibrate (mean 476 mg/day) to 58 patients with elevated total cholesterol and both agents (mean nicotinic acid 435 mg/day and bezafibrate 512 mg/day) to 25 patients with low HDL cholesterol and elevated total cholesterol. A total of 53 additional patients were followed as controls. Three intervals of treatment were studied: 0-6, 6-12 and > 12 months. The combination of drugs resulted in significant (P < 0.05) percentage changes in total cholesterol, triglycerides and total/HDL cholesterol compared to nicotinic acid alone and significant (P < 0.04) percentage changes in HDL cholesterol compared to bezafibrate alone. It is concluded that low doses of nicotinic acid may result in significant changes in HDL cholesterol; when combined with bezafibrate significant alterations in total cholesterol, triglycerides and total/HDL cholesterol also result.

Raising HDL cholesterol without inducing hepatic steatosis and hypertriglyceridemia by a selective LXR modulator
Miao, B., S. Zondlo, et al. (2004), J Lipid Res 45(8): 1410-7.
Abstract: Liver X receptors (LXRs) are ligand-activated transcription factors that belong to the nuclear receptor superfamily. LXRs activate transcription of a spectrum of genes that regulate reverse cholesterol transport, including the ATP binding cassette transporter A1 (ABCA1), and raise HDL cholesterol (HDL-C) levels. However, LXR agonists also induce genes that stimulate lipogenesis, including the sterol response element binding protein (SREBP1-c) and fatty acid synthetase (FAS). The induction of these genes in the liver cause increased hepatic triglyceride synthesis, hypertriglyceridemia, and hepatic steatosis. As LXR response elements have been identified in these promoters, it is not clear if these two processes can be separated. Herein, we demonstrate that plasma HDL-C elevation and intestinal ABCA1 induction can occur with relatively little induction of FAS and SREBP1-c in mouse liver via a selective LXR modulator GW3965. This is in contrast to the strong induction of hepatic lipogenic genes by the well-characterized LXR agonist T0901317 (T317). Consistent with the in vivo results, GW3965 is a very weak LXR activator compared with T317 in human hepatoma cells. GW3965-liganded LXR recruits selected coactivators less effectively than T317 and may explain in part the tissue selective gene induction. This demonstration that tissue and gene selective modulation is possible with selective LXR modulators has positive implications for the development of this class of antiatherosclerotic agents.

Raising high density lipoprotein cholesterol. The biochemical pharmacology of reverse cholesterol transport
Miller, N. E. (1990), Biochem Pharmacol 40(3): 403-10.

Raising high-density lipoprotein cholesterol and lowering low-density lipoprotein cholesterol as adjunctive therapy to coronary artery revascularization
Bates, E. R. (2000), Am J Cardiol 86(12A): 28L-34L.
Abstract: Several studies shortly after the advent of coronary artery bypass surgery reported early atherosclerosis in saphenous vein grafts, and an association between dyslipidemia and graft occlusion. Lipid-lowering therapy in a number of trials resulted in reduced progression of atherosclerosis in vein grafts and fewer subsequent revascularization procedures. Presently, however, only a few patients are treated and reach target lipid levels. Percutaneous coronary interventions permit rapid relief of symptoms and ischemia, and return to full activity levels, but may not reduce the risk of death or nonfatal myocardial infarction in patients with chronic stable coronary artery disease. Whether optimal medical therapy, including aggressive lipid control, could decrease the need for some of these procedures is the subject of ongoing debate and research. Despite successful coronary artery revascularization, subsequent ischemic events continue to occur, supporting the requirement for successful secondary prevention interventions. Ultimately, optimal care of revascularization patients should include maximizing lipid profiles.

Raising high-density lipoprotein cholesterol with niacin and fibrates: a comparative review
Sprecher, D. L. (2000), Am J Cardiol 86(12A): 46L-50L.
Abstract: A growing number of trials that used fibrates and niacin alone or in combination with other lipid-altering agents have shown that both these drugs are effective for reducing total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides, and for increasing high-density lipoprotein cholesterol (HDL-C) levels. These lipid changes are associated with a reduction in events such as fatal and nonfatal myocardial infarction, stroke, and transient ischemic attack. In angiographic trials, they are associated with disease regression, increased minimal luminal diameter, and protection from risk of new lesions. In a head-to-head comparison study, niacin 2,000 mg/day increased HDL-C more than gemfibrozil 1,200 mg/day, and decreased the total cholesterol-to-HDL-C ratio, lipoprotein (a) (Lpa), and fibrinogen levels significantly more. Combination therapies of niacin plus a resin or statin are effective, well tolerated, and safe.

Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid--a position paper developed by the European Consensus Panel on HDL-C
Chapman, M. J., G. Assmann, et al. (2004), Curr Med Res Opin 20(8): 1253-68.
Abstract: Reduction of low-density lipoprotein cholesterol (LDL-C) is presently the primary focus of lipid-lowering therapy for prevention and treatment of coronary heart disease (CHD). However, the high level of residual risk among statin-treated patients in recent coronary prevention studies indicates the need for modification of other major components of the atherogenic lipid profile. There is overwhelming evidence that a low plasma level of high-density lipoprotein cholesterol (HDL-C) is an important independent risk factor for CHD. Moreover, a substantial proportion of patients with or at risk of developing premature CHD typically exhibit distinct lipid abnormalities, including low HDL-C levels. Thus, therapeutic intervention aimed at raising HDL-C, within the context of reducing global cardiovascular risk, would benefit such patients, a viewpoint increasingly adopted by international treatment guidelines. Therapeutic options for patients with low HDL-C include treatment with statins, fibrates and nicotinic acid, either as monotherapy or in combination. Of these options, nicotinic acid is not only the most potent agent for raising HDL-C but is also effective in reducing key atherogenic lipid components including triglyceride-rich lipoproteins (mainly very low-density lipoproteins VLDL and VLDL remnants), LDL-C, and lipoprotein(a). The principal features of the atherogenic lipid profile in type 2 diabetes and the metabolic syndrome make them logical targets for nicotinic acid therapy, either alone or in combination with a statin. The lack of comprehensive European data on the prevalence of low HDL-C levels highlights a critical need for education on the importance of raising HDL-C in CHD prevention and treatment. The development of a reliable and accurate assay for HDL-C, as well as clarification of criteria for low and optimal levels of HDL-C in both men and women, constitute critical factors in the reliable identification and treatment of patients at elevated risk of CHD due to low HDL-C. Based on the available evidence, the European Consensus Panel recommends that the minimum target for HDL-C should be 40 mg/dL (1.03 mmol/L) in patients with CHD or with a high level of risk for CHD, including patients at high global risk with type 2 diabetes or the metabolic syndrome.

Raising high-density lipoprotein cholesterol: innovative strategies against an old adversary
Kazi, D. and J. A. Farmer (2005), Curr Atheroscler Rep 7(2): 88-94.
Abstract: The lipid hypothesis, which was proposed over 100 years ago, is based on the premise that dyslipidemia is central to the process of atherosclerosis. Low-density lipoprotein and lipoprotein(a) are clearly atherogenic, whereas the role of very low-density lipoprotein as an independent factor is controversial. The only lipoprotein that is clearly antiatherogenic is high-density lipoprotein (HDL), which is thought to reduce coronary risk by mediating cholesterol efflux from the periphery by way of transportation to the liver for excretion. Traditionally, fibric acid derivatives and nicotinic acid were the major pharmacologic agents used to raise circulating levels of HDL. Recent therapeutic advances have been made in the ability to increase HDL. Apolipoprotein A-I Milano and cholesterol ester transfer protein represent novel approaches to the pharmacologic therapy of individuals with low HDL levels. The mechanisms and clinical implications of these interventions are discussed here.

Raising low levels of high-density lipoprotein cholesterol is an important target of therapy
Boden, W. E. and T. A. Pearson (2000), Am J Cardiol 85(5): 645-50, A10.
Abstract: Recent clinical trials in patients with coronary heart disease indicate, for the very first time, that increasing low levels of high-density lipoprotein (HDL) cholesterol significantly reduces the cumulative occurrence of cardiovascular and cerebrovascular events in patients whose only lipid abnormality was low HDL with normal levels of low-density lipoprotein (LDL) cholesterol and triglycerides. These data provide a compelling scientific basis for a more targeted and segmental approach to managing patients with dyslipidemia, where decreasing elevated levels of LDL cholesterol and increasing low levels of HDL cholesterol should comprise dual targets of pharmacotherapy.

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Cholesterol Journal Articles