Cholesterol Journal Articles

Record 6581 to 6600

Guinea pigs as models for cholesterol and lipoprotein metabolism
Fernandez, M. L. (2001), J Nutr 131(1): 10-20.
Abstract: Guinea pigs carry the majority of their plasma cholesterol in LDL, making them a unique animal model with which to study hepatic cholesterol and lipoprotein metabolism. In this review, the benefits and advantages of using this particular model are discussed. How dietary factors such as soluble fiber, cholesterol and fatty acids that vary in saturation and chain length affect hepatic cholesterol homeostasis and influence the synthesis, intravascular processing and catabolism of lipoproteins is reviewed. In addition, alterations in hepatic cholesterol metabolism and plasma lipoproteins as affected by treatment with cholestyramine or 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors, exercise, marginal intake of vitamin C, ovariectomy (a model for menopause) and similarities to the human situation are addressed. A review of guinea pigs as models for early atherosclerosis development is also presented.

Gut-acting drugs for lowering cholesterol
Black, D. M. (2002), Curr Atheroscler Rep 4(1): 71-5.
Abstract: Drugs that indirectly lower blood cholesterol through their actions in the gut have been used for many years. Their utility has been limited by poor tolerability, and hence, poor compliance. New resins are better tolerated and offer an advantage to older drugs. New strategies focusing on reducing serum cholesterol by acting on the gastrointestinal tract may hold even greater promise, combining the safety of nonsystemic agents with the acceptance of statins.

Haemodynamically significant plaque formation and regional endothelial dysfunction in cholesterol-fed ApoE-/- mice
Johansson, M. E., U. Hagg, et al. (2005), Clin Sci (Lond) 108(6): 531-8.
Abstract: Flow-mediated vasodilation is suggested as one of the mechanisms involved in arterial expansive remodelling, which is thought to be a defence mechanism in atherogenesis. In the present study, we tested the hypothesis that lumen obstructive plaque formation is associated with failure of NO (nitric oxide)-dependent vasodilation in conduit vessels. Cardiac function and aortic root flow velocities were assessed using high-resolution echocardiography and two-dimensional-guided pulsed Doppler in ApoE(-/-) (apolipoprotein E-deficient) mice fed a standard or high-cholesterol diet. Endothelial function in the proximal and mid-descending aortic regions was studied using a myograph technique. Flow velocity at the aortic root of cholesterol-fed ApoE(-/-) mice was significantly increased as a result of lumen narrowing, detected via histological analysis. NO-dependent vasodilatory responses were selectively impaired in the atherosclerosis-prone vascular regions in cholesterol-fed ApoE(-/-) mice. In conclusion, consumption of a high-cholesterol diet results in lumen obstructive plaque formation in ApoE(-/-) mice, which significantly alters aortic root haemodynamics. This phenomenon is associated with impaired NO-dependent vasodilation in vessel segments known to be prone to atherosclerosis.

Hamsters and guinea pigs differ in their plasma lipoprotein cholesterol distribution when fed diets varying in animal protein, soluble fiber, or cholesterol content
Fernandez, M. L., T. A. Wilson, et al. (1999), J Nutr 129(7): 1323-32.
Abstract: There were two objectives to these studies: 1) to compare the lipoprotein cholesterol distribution in two animal models in response to different dietary treatments and 2) to assess whether the hypercholesterolemia induced by high cholesterol intake could be reversed by consumption of vegetable-protein and/or dietary fiber. Guinea pigs, which carry the majority of plasma cholesterol in LDL, and hamsters, with a higher distribution of cholesterol in HDL, were evaluated in three different studies. In Study 1, animals were fed semi-purified diets for 4 wk with proportions of 60:40, 20:80 or 0:100 (w/w) of casein/ soybean protein. Hamsters and guinea pigs that consumed 100% soybean protein had lower plasma total cholesterol (TC) than those fed diets containing casein (P < 0.01). In Study 2, three doses of dietary pectin (2.7, 5.4, or 10.7 g/100g) added in place of cellulose were tested. Intake of 10.7 g/100 g pectin resulted in the lowest plasma TC concentrations for both species (P < 0.01). Although the TC lowering was similar in studies 1 and 2, the lipoprotein cholesterol distribution differed. Whereas the differences in plasma cholesterol were in LDL in guinea pigs, hamsters exhibited differences in both non-HDL and HDL cholesterol. In study 3, animals were fed 100% soybean protein, 10.7 g/100 g pectin, and three doses of dietary cholesterol: 0.04, 0.08, or 0.16 g/100 g, which is equivalent to 300, 600, or 1,200 mg/d in humans. Guinea pigs and hamsters had the highest plasma LDL and hepatic cholesterol concentrations when they consumed 0.16 g/100 g of cholesterol (P < 0.01). However, intake of 0.08 g/100 g of cholesterol resulted in lower plasma LDL cholesterol concentrations than did consuming high animal protein (60:40 casein/ soy) or low soluble fiber (2.7 g/100 g). Relatively high levels of dietary cholesterol combined with vegetable protein and soluble fiber resulted in desirable lipoprotein profiles in animal models that significantly differ in their lipoprotein cholesterol distribution.

Hamsters fed diets high in saturated fat have increased cholesterol accumulation and cytokine production in the aortic arch compared with cholesterol-fed hamsters with moderately elevated plasma non-HDL cholesterol concentrations
Alexaki, A., T. A. Wilson, et al. (2004), J Nutr 134(2): 410-5.
Abstract: There is growing evidence that dietary fatty acids and/or dietary cholesterol could have a direct role on inflammatory diseases such as atherosclerosis. F(1)B Golden Syrian hamsters (Mesocricetus auratus), in 2 groups of 72, were fed for 10 wk a semipurified diet containing either 20 g/100 g hydrogenated coconut oil without cholesterol or cocoa butter (20 g/100 g) with cholesterol (0.15 g/100 g). After the 10-wk treatment period, plasma was collected from food-deprived hamsters (16 h) for plasma lipid measurements. Hamsters were then ranked according to their plasma VLDL and LDL cholesterol (non-HDL-C) concentrations with 1.86 mmol/L as the cut-off point between low (Low; n = 36) and medium (Med; n = 36) concentrations for each treatment. Hamsters in the Low and Medium groups fed cholesterol (Low-chol) had significantly lower plasma total cholesterol (TC) concentrations than hamsters in the Low group fed coconut oil (Low-CO). However, this difference for the Medium group was reflected in significantly lower plasma HDL cholesterol (HDL-C) concentrations. Hamsters in the Low-CO group had significantly higher aortic total and esterified cholesterol concentrations than hamsters in the Low-chol group. Hamsters in the Low-chol group had significantly higher aortic tumor necrosis factor-alpha concentrations than hamsters in the Low-CO group. Hamsters in the Med-CO group had significantly higher aortic interleukin-1beta concentrations than hamsters in the Med-chol group. In conclusion, the present study suggests that dietary cholesterol and saturated fatty acids could have an effect on atherosclerosis not only beyond their role in affecting plasma lipoproteins but also through increased production of inflammatory cytokines in the arterial wall.

Hamsters predisposed to sucrose-induced cholesterol gallstones (LPN strain) are more resistant to excess dietary cholesterol than hamsters that are not sensitive to cholelithiasis induction
Souidi, M., M. Combettes-Souverain, et al. (2001), J Nutr 131(6): 1803-11.
Abstract: We compared the effects of cholesterol feeding in male hamsters from two strains with different propensities to sucrose-induced cholelithiasis; Laboratoire de Physiologie de la Nutrition (LPN) hamsters are predisposed to developing biliary cholesterol gallstones, whereas Janvier (JAN) hamsters are not. When fed a basal control diet, LPN hamsters had a lower cholesterolemia (-21%, P = 0.01) than JAN hamsters, and a higher activity of 3-hydroxy-3-methyl glutaryl coenzyme A reductase in liver (+148%, P = 0.018) and intestine (+281%, P < 0.0001). After feeding the same diet enriched with 0.3% cholesterol for 5 wk, cholesterolemia increased more dramatically in JAN hamsters (+235%, P < 0.001) than in LPN hamsters (+108%, P < 0.001), as did the liver concentration of cholesterol, which reached 152.30 +/- 13.00 and 44.41 +/- 9.06 micromol/g, respectively. Only JAN hamsters displayed hepatomegaly, with an increased cholesterol saturation index of the gallbladder bile (+100%, P < 0.01), due to the cholesterol challenge. In liver, cholesterol feeding reduced cholesterol 7alpha-hydroxylase activity and mRNA level, and stimulated sterol 27-hydroxylase and oxysterol 7alpha-hydroxylase activities. Hepatic levels of LDL receptor decreased by approximately 60% in both strains, whereas HDL receptor scavenger class B type 1 (SR-BI) levels were unaffected by dietary cholesterol. The greater resistance of LPN hamsters to the hypercholesterolemic diet can be explained by a lower capacity to store cholesterol in the liver and greater efficiency in reducing the activity of 3-hydroxy-3-methyl glutaryl coenzyme A reductase in response to cholesterol feeding from 11263 to 261 pmol/(min x organ) in LPN hamsters and from 4530 to 694 pmol/(min x organ) in JAN hamsters. These results highlight the usefulness of this two-strain model, which offers some analogy with the inverse association between the predisposition to cholelithiasis and the risk of atherosclerosis in humans.

Haplotype analysis of two APOA1/MspI polymorphisms in relation to plasma levels of apo A-I and HDL-cholesterol
Kamboh, M. I., C. E. Aston, et al. (1996), Atherosclerosis 127(2): 255-62.
Abstract: A common MspI polymorphism (G/A) in the promoter region of the APOA1 gene (-75 bp) has been shown to be associated with plasma apo A-I and HDL-C variation in several, but not all, studies. Recently another MspI polymorphic site (+/-) in the 5'region of APOA1 (+83 bp) has been identified which may also be relevant to HDL metabolism. This study was undertaken to elucidate the individual and combined effects of these two polymorphisms on plasma apo A-I and HDL-C levels in a cohort of 534 normoglycemic US Whites from the San Luis Valley, Colorado. Both polymorphisms were in strong linkage disequilibrium (P < 0.005); of the expected four haplotypes (G+, G-, A+, A-) the A- was not observed in this sample. Single site RFLP analysis revealed an independent and significant effect associated with each polymorphism on plasma apo A-I variation but not on HDL-C variation. Further analyses showed that the genotype effects of both polymorphisms were confined to non-smokers only. Haplotype analysis, combining both RFLPs, was more informative as this explained almost twice the amount of phenotypic variation in plasma apo A-I compared to single RFLP analysis in non-smokers. Compared to the most common haplotype (G+), the A+ and G- haplotypes were associated with increased plasma apo A-I levels by 6.7 mg/dl and 22.0 mg/dl, respectively in non-smoking men, and by 4.6 mg/dl and 15.1 mg/dl in non-smoking women, respectively. These data indicate that haplotype analysis in this region may be important to elucidate the functional significance of the APOA1 gene in HDL metabolism.

Haplotypes and SNPs in 13 lipid-relevant genes explain most of the genetic variance in high-density lipoprotein and low-density lipoprotein cholesterol
Knoblauch, H., A. Bauerfeind, et al. (2004), Hum Mol Genet 13(10): 993-1004.
Abstract: Single nucleotide polymorphisms (SNPs) and derived haplotypes within multiple genes may explain genetic variance in complex traits; however, this hypothesis has not been rigorously tested. In an earlier study we analyzed six genes and have now expanded this investigation to include 13. We studied 250 families including 1054 individuals and measured lipid phenotypes. We focused on low-density cholesterol (LDL), high-density cholesterol (HDL) and their ratio (LDL/HDL). A component analysis of the phenotypic variance relying on a standard genetic model' showed that the genetic variance on LDL explained 26%, on HDL explained 38% and on LDL/HDL explained 28% of the total variance, respectively. Genotyping of 93 SNPs in 13 lipid-relevant genes generated 230 haplotypes. The association of haplotypes in all the genes tested explained a major fraction of the genetic phenotypic variance component. For LDL, the association with haplotypes explained 67% and for HDL 58% of the genetic variance relative to the polygenic background. We conclude that these haplotypes explain most of the genetic variance in LDL, HDL and LDL/HDL in these representative German families. An analysis of the contribution to the genetic variance at each locus showed that APOE (50%), CETP (28%), LIPC (9%), APOB (8%) and LDLR (5%) influenced variation in LDL. LIPC (53%), CETP (25%), ABCA1 (10%), LPL (6%) and LDLR (6%) influenced the HDL variance. The LDL/HDL ratio was primarily influenced by APOE (36%), CETP (27%) and LIPC (31%). This expanded analysis substantially increases the explanation of genetic variance on these complex traits.

Harbingers of coronary heart disease: dietary saturated fatty acids and cholesterol. Is chocolate benign because of its stearic acid content?
Connor, W. E. (1999), Am J Clin Nutr 70(6): 951-2.

Harmonization of methods for analysis of cholesterol oxides in foods--the first portion of a long road toward standardization: interlaboratory study
Appelqvist, L. A., P. Addis, et al. (2004), J AOAC Int 87(2): 511-9.
Abstract: A compilation of literature data on the content of cholesterol oxidation products (COP) in various food products and in blood demonstrates a large variation in content in products or tissues of very similar nature when analyzed in different laboratories according to a large number of methods. The lack of validated, internationally recognized methodology with published accuracy and precision has so far hindered such assessments. Hence an interlaboratory comparision of methodologies of COP analysis was undertaken on egg yolk powders (EYP), whole milk powders (WMP), skim milk powders (SMP), and lard (L). Each product type had one fresh sample (low) and one aged (high) in COP contents. A total of 17 sets of results on WMP, 15 on SMP and EYP, and 13 on L were compared. Overall results (mg/kg sample) varied extensively: Fresh EYP 0.72-265, aged EYP 2.51-361; fresh WMP 0.02-18.1, aged WMP 0.02-26.9; fresh SMP 0.02-6.51, aged SMP <0.01-6.51; fresh L 0.18-97, aged L 4.15-452. Some results were questioned, viz., those from laboratories not indicating substantial differences between samples "low" and "high" in total COP. Others were excluded because of lack of verification of identity of gas chromatographic peaks by mass spectrometry. Then a more narrow range of core results (mg/kg sample) was observed: Fresh EYP 5.69-29.5 sample, aged EYP 11.8-79.0; fresh WMP 0.12-1.76, aged WMP 1.17-13.7; fresh SMP <0.30-<1.21, aged SMP 0.30-2.26; fresh L 0.18-5.07, aged L 94.4-231. At a workshop discussing the results, numerous recommendations were made toward more reliable methodology for determination of COP in foods.

Has nature designed the cholesterol side chain for optimal interaction with phospholipids?
Bittman, R. (1997), Subcell Biochem 28: 145-71.

Has westernization influenced serum cholesterol levels in Bougainvillian males?
Iser, D. J. and K. Avera (1993), P N G Med J 36(4): 311-5.
Abstract: This study was performed to see if there was any difference in cholesterol levels between three socioeconomic groups of Bougainvillian males, each with different levels of exposure to western influences. Serum cholesterol levels were measured in 50 subjects from each of 1) village people leading a traditional lifestyle, 2) town dwellers exposed to western influences, and 3) mine workers who regularly dined in the company mess. Mean cholesterol levels were significantly higher in the mine workers (5.3 +/- SD 0.9 mmol/l) and the town dwellers (4.8 +/- SD 0.8 mmol/l) than in the village people (3.7 +/- SD 1.0 mmol/l). There was a positive correlation between serum cholesterol level and age in two groups, the town dwellers and the village people, even though the latter group had a low mean cholesterol level. There was a significant correlation between body mass index (BMI) and serum cholesterol level for the entire group as well as the town dwellers and mine workers. The higher mean cholesterol levels in the mine workers and town dwellers than in the village people may reflect a difference in lifestyle, particularly in diet, between these groups, and may represent an increased risk for ischaemic heart disease.

Have we forgotten the pivotal role of high-density lipoprotein cholesterol in atherosclerosis prevention?
Wierzbicki, A. S. (2005), Curr Med Res Opin 21(2): 299-306.
Abstract: The critical importance of high-density lipoprotein cholesterol (HDL-C) as an independent and predictive factor for coronary heart disease (CHD) has been increasingly recognised in treatment guidelines for prevention and treatment of cardiovascular disease. The association of low HDL-C with an increased incidence of CHD implies a critical role for raising HDL-C in protection against atherosclerotic disease. HDL-C appears to exert this effect via a number of mechanisms. HDL-C is involved in reverse cholesterol transport, prevents endothelial dysfunction and has anti-inflammatory, anti-oxidant and antithrombotic properties. Therapeutic interventions that increase HDL-C include statins, fibrates and nicotinic acid. Of these, nicotinic acid raises HDL-C more effectively than either statin or fibrate therapy and has been proven to reduce cardiovascular events in monotherapy studies. Preliminary clinical studies have shown that addition of nicotinic acid to primary statin therapy is safe, has proven beneficial effects on atherosclerosis and may also reduce the incidence of major coronary events. The available clinical evidence suggests that addition of nicotinic acid to primary lipid-lowering therapy has an important atheroprotective role in patients with or at risk of developing CHD.

Having too much evidence (depression, suicide, and low serum cholesterol)
Law, M. (1996), Bmj 313(7058): 651-2.

Hawthorn fruit is hypolipidemic in rabbits fed a high cholesterol diet
Zhang, Z., W. K. Ho, et al. (2002), J Nutr 132(1): 5-10.
Abstract: The present study examined the hypolipidemic activity of hawthorn fruit. New Zealand white rabbits were fed one of three diets, a reference diet with no cholesterol added (NC), a high cholesterol diet (1 g/100 g, HC) and a HC diet supplemented with 2 g/100 g hawthorn fruit powder (HC-H). After 12 wk, serum total cholesterol (TC) and triacylglycerols (TG) were 23.4 and 22.2% lower, respectively, in the hawthorn fruit group compared with the HC rabbits (P < 0.05). Hawthorn supplementation led to 50.6% less cholesterol accumulation in aorta (P < 0.05) and 23-95% greater excretion of neutral and acidic sterols (P < 0.05). Supplementation of hawthorn fruit did not affect the activities of hepatic 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG-CoA-R) or cholesterol 7alpha-hydroxylase (CH) but it suppressed the activity of intestinal acyl CoA:cholesterol acyltransferase (ACAT, P < 0.05). The results suggest that the mechanism by which hawthorn fruit decreases serum cholesterol involves, at least in part, the inhibition of cholesterol absorption mediated by down-regulation of intestinal ACAT activity.

Hazards of reducing cholesterol
Lines, C. (1994), Bmj 309(6953): 541.

Hazelnut oil administration reduces aortic cholesterol accumulation and lipid peroxides in the plasma, liver, and aorta of rabbits fed a high-cholesterol diet
Hatipoglu, A., O. Kanbagli, et al. (2004), Biosci Biotechnol Biochem 68(10): 2050-7.
Abstract: Hazelnut oil (HO) is rich in monounsaturated fatty acids and antioxidants. We wanted to investigate the effect of HO on lipid levels and prooxidant-antioxidant status in rabbits fed a high-cholesterol (HC) diet. An HC diet caused significant increases in lipids and lipid peroxide levels in the plasma, liver, and aorta together with histopathological atherosclerotic changes in the aorta. Glutathione levels, glutathione peroxidase, and glutathione transferase activities decreased significantly, but superoxide dismutase activity and vitamin E and C levels remained unchanged in the livers of rabbits following HC diet. HO supplementation reduced plasma, liver, and aorta lipid peroxide levels and aorta cholesterol levels together with amelioration in atherosclerotic lesions in the aortas of rabbits fed an HC diet, without any decreasing effect on cholesterol levels in the plasma or liver. HO did not alter the antioxidant system in the liver in the HC group. Our findings indicate that HO reduced oxidative stress and cholesterol accumulation in the aortas of rabbits fed an HC diet.

Hazelnut supplementation enhances plasma antioxidant potential and lowers plasma cholesterol levels
Durak, I., I. Koksal, et al. (1999), Clin Chim Acta 284(1): 113-5.

HDL and reverse cholesterol transport. Role of cholesterol ester transfer protein
Lagrost, L. and P. Gambert (1992), C R Seances Soc Biol Fil 186(4): 405-13.
Abstract: As most of peripheral cells are not able to catabolize cholesterol, the transport of cholesterol excess from peripheral tissues back to the liver, namely "reverse cholesterol transport", is the only way by which cholesterol homeostasis is maintained in vivo. Reverse cholesterol transport pathway can be divided in three major steps: 1) uptake of cellular cholesterol by the high density lipoproteins (HDL), 2) esterification of HDL cholesterol by the lecithin: cholesterol acyltransferase and 3) captation of HDL cholesteryl esters by the liver where cholesterol can be metabolized and excreted in the bile. In several species, including man, cholesteryl esters in HDL can also follow an alternative pathway which consists in their transfer from HDL to very low density (VLDL) and low density (LDL) lipoproteins. The transfer of cholesteryl esters to LDL, catalyzed by the Cholesteryl Ester Transfer Protein (CETP), might affect either favorably or unfavorably the reverse cholesterol transport pathway, depending on whether LDL are finally taken up by the liver or by peripheral tissues, respectively. In order to understand precisely the implication of CETP in reverse cholesterol transport, it is essential to determine its role in HDL metabolism, to know the potential regulation of its activity and to identify the mechanism by which it interacts with lipoprotein substrates. Results from recent studies have demonstrated that CETP can promote the size redistribution of HDL particles. This may be an important process in the reverse cholesterol transport pathway as HDL particles with various sizes have been shown to differ in their ability to promote cholesterol efflux from peripheral cells and to interact with lecithin: cholesterol acyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)

HDL apolipoproteins and ABCA1: partners in the removal of excess cellular cholesterol
Oram, J. F. (2003), Arterioscler Thromb Vasc Biol 23(5): 720-7.
Abstract: It is widely believed that HDL protects against atherosclerosis by removing excess cholesterol from arterial cells. Lipid-poor HDL apolipoproteins promote efflux of cholesterol, phospholipids, and other lipophilic molecules from cells by an active process mediated by a cell-membrane transporter called the ATP binding cassette transporter A-1 (ABCA1). ABCA1 either directly or indirectly translocates phospholipids and cholesterol to the cell surface, where they appear to form lipid domains that interact with amphipathic alpha-helixes in apolipoproteins. This interaction solubilizes these lipids and generates nascent HDL particles that dissociate from the cell. Binding of apolipoproteins to ABCA1 may also enhance the activity of this lipid-transport pathway. Thus, the apolipoprotein/ABCA1 pathway efficiently clears cells of excess cholesterol that would otherwise accumulate as intracellular lipid droplets. ABCA1 expression is highly induced by cholesterol loading of cells and is also modulated by sterol-independent mechanisms at both the transcriptional and posttranslational level. Studies of human disease and animal models have shown that both an increased availability of apolipoproteins and an enhanced macrophage ABCA1 activity are atheroprotective. These findings implicate the apolipoprotein/ABCA1 pathway as an important therapeutic target for treating cardiovascular disease.

Cholesterol Articles and Abstracts

Cholesterol Journal Articles