Cholesterol Journal Articles

Record 8181 to 8200

LDL cholesterol: its regulation and manipulation
Dietschy, J. M. (1990), Hosp Pract (Off Ed) 25(6): 67-78.
Abstract: Elevated plasma LDL cholesterol concentrations result primarily from two mechanisms: LDL overproduction and loss of hepatic receptor-dependent LDL removal. This knowledge can be used to lower plasma cholesterol and thereby retard or even reverse atherosclerosis. Pharmacologic agents are useful, as are dietary approaches.

LDL cholesterol-raising effect of low-dose docosahexaenoic acid in middle-aged men and women
Theobald, H. E., P. J. Chowienczyk, et al. (2004), Am J Clin Nutr 79(4): 558-63.
Abstract: BACKGROUND: Long-chain n-3 polyunsaturated fatty acids have variable effects on LDL cholesterol, and the effects of docosahexaenoic acid (DHA) are uncertain. OBJECTIVE: The objective of the study was to determine the effect on blood lipids of a daily intake of 0.7 g DHA as triacylglycerol in middle-aged men and women. DESIGN: Men and women aged 40-65 y (n = 38) underwent a double-blind, randomized, placebo-controlled, crossover trial of treatment with 0.7 g DHA/d for 3 mo. RESULTS: DHA supplementation increased the DHA concentration in plasma by 76% (P < 0.0001) and the proportion in erythrocyte lipids by 58% (P < 0.0001). Values for serum total cholesterol, LDL cholesterol, and plasma apolipoprotein B concentrations were 4.2% (0.22 mmol/L; P = 0.04), 7.1% (0.23 mmol/L; P = 0.004), and 3.4% (P = 0.03) higher, respectively, with DHA treatment than with placebo. In addition, the LDL cholesterol:apolipoprotein B ratio was 3.1% higher with DHA treatment than with placebo (P = 0.04), which suggested an increase in LDL size. Plasma lathosterol and plant sterol concentrations were unaffected by treatment. CONCLUSION: A daily intake of approximately 0.7 g DHA increases LDL cholesterol by 7% in middle-aged men and women. It is suggested that DHA down-regulates the expression of the LDL receptor.

LDL inhibits the mediation of cholesterol efflux from macrophage foam cells by apoA-I-containing lipoproteins. A putative mechanism for foam cell formation
Nakamura, R., T. Ohta, et al. (1993), Arterioscler Thromb 13(9): 1307-16.
Abstract: Although the accumulation of cholesterol in macrophages appears to be an initial step in atherogenesis, low-density lipoprotein (LDL), a major risk factor for atherosclerosis, does not promote cholesterol accumulation in macrophages in its native form. On the other hand, apolipoprotein (apo) A-I-containing lipoprotein removes cholesterol from cholesterol-loaded macrophages (foam cells) and prevents cholesterol from accumulating in the cells. We examined the effect of LDL on cholesterol removal by two species of apoA-I-containing lipoproteins, one containing only apoA-I (LpA-I) and the other containing apoA-I and apoA-II (LpA-I/A-II). When foam cells were incubated with LpA-I or LpA-I/A-II, cellular cholesterol mass was reduced. In contrast, when LDL was added, the cholesterol-reducing capacities of these lipoproteins were dose-dependently inhibited by LDL. In the presence of LDL, LpA-I and LpA-I/A-II removed free cholesterol preferentially from LDL rather than from the plasma membrane of foam cells. In addition, a fair amount of cellular cholesterol was directly moved to LDL rather than to LpA-I or LpA-I/A-II. The cellular cholesterol that moved to LDL was completely compensated for by the cholesterol influx from LDL to foam cells. Thus, net cholesterol efflux (a combination of influx and efflux) from foam cells was inhibited by LDL. These results, taken together, indicate that LDL may accelerate foam cell formation by inhibiting cholesterol removal from the cells and that elevated levels of plasma LDL may become a risk factor for atherosclerosis by inhibiting the function of LpA-I and LpA-I/A-II at the cellular level.

LDL particle size and LDL and HDL cholesterol changes with dietary fat and cholesterol in healthy subjects
Clifton, P. M., M. Noakes, et al. (1998), J Lipid Res 39(9): 1799-804.
Abstract: We have conducted a dietary trial in 54 men and 51 women with a wide range of fasting cholesterol values to examine the use of low density lipoprotein (LDL) particle size to predict the lipoprotein response to dietary fat and cholesterol. After a 2-week low fat period, subjects were given two liquid supplements in addition to their low fat diet for 3 weeks each, one containing 31-40 g of fat and 650-845 mg of cholesterol, the other fat free. LDL particle type was determined by 3-15% gradient gel electrophoresis. On multiple regression, LDL type was independently related to plasma triglyceride (P < 0.001), waist circumference (P < 0.01), and high density lipoprotein (HDL) (P < 0.001) accounting for 56% of the variance in LDL type in the whole group. Change in LDL cholesterol with dietary fat and cholesterol was unrelated to LDL particle size in either men or women. However, change in HDL cholesterol in men was strongly related to LDL particle type (r = -0.52, P = 0.001) and change in HDL2 cholesterol in women was related to LDL particle type (r = -0.40, P < 0.01). In conclusion, we are unable to confirm the finding that LDL particle type can predict changes in LDL cholesterol following changes in dietary fat intake. However, LDL particle type can independently predict changes in HDL cholesterol in men and accounts for 27% of the variance.

LDL particle size by gradient-gel electrophoresis cannot be estimated by LDL-cholesterol/apolipoprotein B ratios
Furuya, D., A. Yagihashi, et al. (2000), Clin Chem 46(8 Pt 1): 1202-3.

LDL receptor activity is down-regulated similarly by a cholesterol-containing diet high in palmitic acid or high in lauric and myristic acids in cynomolgus monkeys
Stucchi, A. F., A. H. Terpstra, et al. (1995), J Nutr 125(8): 2055-63.
Abstract: To determine the mechanisms whereby diets differing widely in fatty acid composition affect plasma LDL cholesterol and apolipoprotein B concentrations, LDL kinetics and receptor- and nonreceptor-mediated LDL catabolism were investigated in 27 cynomolgus monkeys fed diets containing 0.05 mg cholesterol/kJ and 40% fat energy as corn oil alone (unsaturated fat diet rich in oleic and linoleic acids), nonhydrogenated coconut oil alone (saturated fat diet, rich in lauric and myristic acids) or an oil blend (rich in palmitic acid). Consumption of the oil blend and saturated fat diets significantly elevated total cholesterol, LDL cholesterol and apolipoprotein B concentrations relative to the unsaturated fat diet and the saturated fat diet significantly increased plasma total cholesterol and LDL cholesterol compared with the oil blend diet. However, despite the greater increases in plasma total cholesterol, LDL cholesterol and apolipoprotein B in the saturated fat vs. the oil blend dietary group, the receptor-mediated LDL fractional catabolic rate was comparable in the oil blend and saturated fat diet groups. In addition, consumption of the oil blend or saturated fat diet increased the production rate of LDL apolipoprotein B and nonreceptor-mediated LDL apolipoprotein B transport (disposal) relative to the unsaturated fat diet. Our data, therefore, suggest that consumption of the oil blend or saturated fat diet elevated plasma total cholesterol and LDL cholesterol relative to the unsaturated fat diet, and the oil blend diet abundant in palmitic acid seems to have down-regulated the LDL receptor as much as a more saturated fat diet abundant in lauric and myristic acids.

LDL structure and Lp(a) formation: the role of lecithin:cholesterol acyltransferase
Steyrer, E., S. Frank, et al. (1996), Z Gastroenterol 34 Suppl 3: 39-40.

LDL-cholesterol
Sakurabayashi, I. (1999), Nippon Rinsho 57 Suppl: 20-3.

LDL-cholesterol and HDL-cholesterol concentrations decrease during the day
Miida, T., Y. Nakamura, et al. (2002), Ann Clin Biochem 39(Pt 3): 241-9.
Abstract: BACKGROUND: Homogenous assays for LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) are highly accurate, with little interference from triglyceride. Using these methods, we measured postprandial LDL-C and HDL-C. Earlier studies suggested a postprandial decrease in LDL-C. METHODS: To elucidate whether LDL-C and HDL-C decrease significantly during the day, we determined daily profiles of LDL-C and HDL-C using homogeneous assays in subjects with normal coronary arteries (N; n=10), and subjects with coronary artery disease (CAD; n=23). RESULTS: In both groups, LDL-C and HDL-C were significantly lower from after breakfast until midnight than they were before breakfast. The next morning, they returned to baseline levels. The mean reduction in LDL-C was 0.09-0.13 mmol/L in N and 0.05-0.20 mmol/L in CAD, while that in HDL-C was 0.02-0.06 mmol/L in N and 0.00-0.05 mmol/L in CAD. CONCLUSION: LDL-C and HDL-C decrease significantly over the course of the day.

LDL-cholesterol as a determinant of coronary heart disease
Hunninghake, D. (1990), Clin Ther 12(5): 370-5; discussion 369.
Abstract: The Adult Treatment Panel of the National Cholesterol Education Program identified high levels of LDL-cholesterol as a major risk factor in developing CHD and as the primary target for cholesterol-lowering therapy. Low levels of HDL were recognized as a contributing risk factor for CHD, and the panel recommended that low HDL-cholesterol levels be raised by changes in diet and lifestyle. When drug therapy is required for high LDL-cholesterol levels in the presence of low HDL levels, it would appear reasonable to choose one that both markedly reduces LDL-cholesterol and raises HDL-cholesterol.

LDL-cholesterol equations and SI units
Tinker, L. F. (1991), Am J Clin Nutr 53(4): 982-3.

LDL-cholesterol lowering and atherosclerosis--clinical benefit and possible mechanisms: an update
Kroon, A. A. and A. F. Stalenhoef (1997), Neth J Med 51(1): 16-27.
Abstract: The results of several lipid-lowering randomized trials have been released during the past years and have confirmed the lipid hypothesis. Reduction of cholesterol by potent drugs in clinically symptomatic or asymptomatic patients with above-average cholesterol levels will substantially reduce the risk of coronary events. The present article gives a review of potent low-density lipoprotein cholesterol-lowering treatments and discusses developments in hypolipidaemic therapy in relation to recent primary and secondary prevention studies. In addition, possible mechanisms of cholesterol lowering in retardation of the atherosclerotic process are summarised.

LDL-cholesterol lowering effect of a generic product of simvastatin compared to simvastatin (Zocor) in Thai hypercholesterolemic subjects -- a randomized crossover study, the first report from Thailand
Wiwanitkit, V., D. Wangsaturaka, et al. (2002), BMC Clin Pharmacol 2: 1.
Abstract: BACKGROUND: It is commonly agreed that people with a high blood LDL-cholesterol will have a higher risk of coronary artery disease (CAD) than people with low blood LDL-cholesterol. Due to the increasingly high costs of medication in Thailand, the government has set up several measures to combat the problem. One of such strategies is to promote the utilization of locally manufactured drug products, especially those contained in the National Drug List. Simvastatin, an HMG-CoA reductase inhibitor, is listed as an essential drug for the treatment of hypercholesterolemia. Here, we reported the study on the LDL-cholesterol-lowering effect of a generic simvastatin product in comparison with the Zocor, in 43 healthy thai volunteers. METHOD: The generic product tested was Eucor, locally manufactured by Greater Pharma Ltd., Part, Thailand, and the reference product was Zocor (Merck Sharp & Dohme, USA). The two products were administered as 10-mg single oral doses in a two-period crossover design. After drug administration, serial blood samples were collected every 4 weeks for 16 weeks. The major parameter monitored in this study was blood LDL-cholesterol. RESULT: After taking the drugs for the first 8 weeks, no statistically significant difference was detected in blood LDL-cholesterol between the first (Zocor-treated) and the second (Eucor-treated) groups. After crossover and taking drugs for further 8 weeks, a similar result was obtained, i.e., no significant difference in blood LDL-cholesterol between the first (Eucor-treated) and the second (Zocor-treated) groups was observed. Upon completion of the 16-week study, there was also no statistically significant difference in the changes of all tested blood parameters between the two products (randomized block ANOVA, N = 37). Only minor side effects, mainly dizziness and nausea, were observed in both products. CONCLUSION: Our study demonstrated no significant differences in the therapeutic effect and safety between the generic and original simvastatin products.

LDL-cholesterol, HDL-cholesterol or triglycerides--which is the culprit?
Taskinen, M. R. (2003), Diabetes Res Clin Pract 61 Suppl 1: S19-26.
Abstract: Dyslipidaemia in patients with type 2 diabetes commonly consists of elevated triglyceride levels; normal or slightly elevated low-density lipoprotein (LDL)-cholesterol levels with a preponderance of small, dense LDL particles; and low high-density lipoprotein (HDL)-cholesterol levels with a preponderance of small, dense HDL. These abnormalities are closely connected, with prolonged residence of high levels of triglyceride-rich particles in the circulation favoring abnormalities in LDL and HDL. Each of these factors has been associated with endothelial dysfunction; each contributes directly or indirectly to atheroma formation, with small, dense LDL and triglyceride-rich remnants increasing deposition of cholesteryl ester in vessel walls. This process is facilitated by reduced reverse cholesterol transport in association with low levels of HDL-cholesterol and abnormal HDL. Lipid-lowering therapy focused on LDL-cholesterol reduction is highly successful in preventing coronary disease in diabetic patients. Additional strategies for treating the cluster of risk factors in dyslipidaemia are necessary to further reduce atherosclerotic disease in this population.

LDL-cholesterol/apolipoprotein B ratio is a good predictor of LDL phenotype B in type 2 diabetes
Wagner, A. M., O. Jorba, et al. (2002), Acta Diabetol 39(4): 215-20.
Abstract: LDL phenotype B is a component of diabetic dyslipidaemia, but its diagnosis is cumbersome. Our aim was to find easily available markers of phenotype B in a group of type 2 diabetic subjects. We studied 123 type 2 diabetic patients (67.5% male, aged 59.3+/-10.1 years, mean HbA1c 7.4%). Clinical features and fasting total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol (LDLc, using Friedewald's equation and an alternative formula), apolipoprotein B (apoB), lipoprotein (a) and LDL particle size (on gradient polyacrylamide gel electrophoresis) were assessed. Patients with phenotypes A (predominant LDL size > or =25.5 nm) and B (<25.5 nm) were compared, and regression analysis was performed to find the best markers of LDL particle. Cut-off points were obtained and evaluated as predictors of phenotype B (kappa index). Patients with phenotype B (36%) showed higher total cholesterol, triglyceride and apolipoprotein B, and lower HDL cholesterol and LDLc/apoB ratio. Triglyceride was the best predictor of LDL particle size (r=-0.632, p<0.01), but an LDLc/apoB ratio below 1.297 mmol/g detected phenotype B best (sensitivity 65.9%, specificity 92.4%, kappa=0.611). Although triglyceride concentration is the best predictor of LDL size in type 2 diabetes, LDLcholesterol/apolipoproteinB ratio is the best tool to detect phenotype B.

LDL-cholesterol: a risk factor for coronary artery disease--from epidemiology to clinical trials
Werner, R. M. and T. A. Pearson (1998), Can J Cardiol 14 Suppl B: 3B-10B.
Abstract: Discussion of potential strategies to modify lipids and lipoproteins other than low density lipoproteins (LDLs) should first recognize the convincing evidence in favour of the identification and aggressive treatment of elevated LDL cholesterol (LDL-C) levels in patients with established cardiovascular disease. Elevated LDL-C level is one of the few risk factors for which there is evidence of involvement in every pathophysiological step of the development of cardiovascular disease. Longitudinal studies have established the role of LDL-C as a risk factor for cardiovascular disease incidence, recurrence and fatal outcome. Clinical trials and economic analyses have proven that aggressive treatment of elevated LDL-C in patients at high risk can prevent cardiac events with excellent cost effectiveness.

LDL-cholesterol-lowering effect of a mixed green vegetable and fruit beverage containing broccoli and cabbage in hypercholesterolemic subjects
Takai, M., H. Suido, et al. (2003), Rinsho Byori 51(11): 1073-83.
Abstract: The serum LDL-cholesterol (LDL-C)-lowering effects of two types of canned beverage containing mixed green vegetables and fruits, with or without broccoli and cabbage (B&C), were examined in a randomized double-blind study design. Seventy-seven adults subjects with mild to moderate hypercholesterolemia participated in this study after giving their informed consent. The subjects were randomly divided into two groups. One group(test group) was allocated a test sample, containing B&C as the main materials. Another group(control group) was allocated a placebo sample made from the same materials but without B&C. The subjects were administered 2 cans of the assigned sample (160 g contents/can) per day for 12 weeks. Forty-nine out of 77 subjects, whose LDL-C levels were greater than or equal to 140 mg/dl and less than 180 mg/dl, were analyzed for the effectiveness. Serum LDL-C levels in the test group were significantly(p < 0.05) reduced at 3, 6 and 9 weeks after administration in comparison to the baseline levels (155.7 mg/dl in average). The average LDL-C value at 9 weeks was 142.5 mg/dl and the reduction rate was 8.5%. But serum LDL-C levels in the control group were not significantly reduced. Significant differences(p < 0.05) between the groups were observed in the LDL-C levels at 6 and 9 weeks and also in the total cholesterol levels at 9 week. Thus daily intake of the beverage tested containing B&C are useful for lowering serum LDL-C levels in hypercholesterolemic subjects.

Lead nitrate-induced development of hypercholesterolemia in rats: sterol-independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis
Kojima, M., T. Masui, et al. (2004), Toxicol Lett 154(1-2): 35-44.
Abstract: Changes in the gene expressions of hepatic enzymes responsible for cholesterol homeostasis were examined during the process of lead nitrate (LN)-induced development of hypercholesterolemia in male rats. Total cholesterol levels in the liver and serum were significantly increased at 3-72 h and 12-72 h, respectively, after LN-treatment (100 micromol/kg, i.v.). Despite the development of hypercholesterolemia, the genes for hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and other enzymes (FPPS, farnesyl diphosphate synthase; SQS, squalene synthase; CYP51, lanosterol 14alpha-demethylase) responsible for cholesterol biosynthesis were activated at 3-24 h and 12-18 h, respectively. On the other hand, the gene expression of cholesterol 7alpha-hydroxylase (CYP7A1), a catabolic enzyme of cholesterol, was remarkably suppressed at 3-72 h. The gene expression levels of cytokines interleukin-1beta (IL-1beta) and TNF-alpha, which activate the HMGR gene and suppress the CYP7A1 gene, were significantly increased at 1-3 h and 3-24 h, respectively. Furthermore, gene activation of SREBP-2, a gene activator of several cholesterogenic enzymes, occurred before the gene activations of FPPS, SQS and CYP51. This is the first report demonstrating sterol-independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis in LN-treated male rats. The mechanisms for the altered-gene expressions of hepatic enzymes in LN-treated rats are discussed.

Lecithin cholesterol acyltransferase
Jonas, A. (2000), Biochim Biophys Acta 1529(1-3): 245-56.
Abstract: Cholesterol transport in circulation and its removal from tissues depends on the activity of lecithin cholesterol acyltransferase (LCAT). LCAT is a soluble enzyme that converts cholesterol and phosphatidylcholines (lecithins) to cholesteryl esters and lyso-phosphatidylcholines on the surface of high-density lipoproteins. This review presents key background information and recent research advances on the structure of human LCAT, its reactions and substrates, and the expression of the LCAT gene. While the three-dimensional structure of LCAT is not yet known, a partial model now exists that facilitates the study of structure-function relationships of the native enzyme, and of natural and engineered mutants. The LCAT reaction on lipoproteins consists of several steps, starting with enzyme binding to the lipoprotein/lipid surface, followed by activation of LCAT by apolipoproteins, binding of lipid substrates and the catalytic steps giving rise to the lipid products. Quantitative data are presented on the kinetic and equilibrium constants of some of the LCAT reaction steps. Finally, overexpression of the human LCAT gene in mice and rabbits has been used to examine the physiologic role of LCAT in vivo and its protective effect against diet induced atherosclerosis.

Lecithin cholesterol acyltransferase activity in acute lymphoblastic leukemia
Ahaneku, J. E., I. E. Okpala, et al. (1991), Leukemia 5(11): 1004-5.
Abstract: Lecithin cholesterol acyltransferase (LCAT) activity and free cholesterol and cholesterol ester concentrations were determined in serum samples from 28 patients with acute lymphoblastic leukemia (ALL) and in an equal number of healthy controls. No significant alterations in LCAT activity, free cholesterol, or esterified cholesterol levels were observed in the ALL patients compared with the controls.

Cholesterol Articles and Abstracts

Cholesterol Journal Articles