| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| The myeloperoxidase product hypochlorous acid oxidizes HDL in the human artery wall and impairs ABCA1-dependent cholesterol transport Bergt, C., S. Pennathur, et al. (2004), Proc Natl Acad Sci U S A 101(35): 13032-7. Abstract: Although oxidatively damaged lipoproteins are implicated in vascular injury, there is little information regarding the role of high-density lipoprotein (HDL) oxidation in atherogenesis. One potential pathway involves hypochlorous acid (HOCl) produced by myeloperoxidase (MPO), a heme protein secreted by phagocytes. We previously showed that 3-chlorotyrosine is a specific product of HOCl. Therefore, to explore the role of oxidized HDL in the pathogenesis of vascular disease, we used MS to quantify 3-chlorotyrosine in HDL isolated from plasma and atherosclerotic tissue. HDL from human aortic atherosclerotic intima had an 8-fold higher level of 3-chlorotyrosine than plasma HDL. Tandem MS analysis identified MPO as a component of lesion HDL, suggesting that the two interact in the artery wall. Moreover, immunohistochemical studies found that specific epitopes derived from HOCl colocalized with apolipoprotein A-I, the major protein of HDL. These observations strongly support the hypothesis that MPO promotes HDL oxidation in the human artery wall. Levels of 3-chlorotyrosine were elevated in HDL isolated from the blood of humans with established coronary artery disease, suggesting that circulating levels of oxidized HDL represent a unique marker for clinically significant atherosclerosis. HDL or lipid-free apolipoprotein A-I exposed to HOCl was less able to remove cholesterol from cultured cells by a pathway requiring the cell membrane transporter ATP-binding cassette transporter A1. The detection of 3-chlorotyrosine in HDL isolated from vascular lesions raises the possibility that MPO, by virtue of its ability to form HOCl, may promote atherogenesis by counteracting the established antiatherogenic effects of HDL and the ATP-binding cassette transporter A1 pathway. |
| The mysteries of sigma receptors: new family members reveal a role in cholesterol synthesis Moebius, F. F., J. Striessnig, et al. (1997), Trends Pharmacol Sci 18(3): 67-70. |
| The National Cholesterol Education Program Brown, V. (1990), Arzneimittelforschung 40(3A): 395-9. Abstract: Following a recommendation by the US Consensus Conference of December 1984, a National Cholesterol Education Program was initiated by about 30 different organizations. This program mainly addresses health professionals, such as physicians, nurses, dietitians etc. One of its objectives is to give physicians clear guidelines as to type and timing of interventions (diet, drugs). The program further comprises an extensive advertising campaign with the aim of reducing risk factors mainly by popularizing health-oriented nutrition. |
| The National Cholesterol Education Program Adult Treatment Panel III guidelines Lipsy, R. J. (2003), J Manag Care Pharm 9(1 Suppl): 2-5. Abstract: Coronary heart disease (CHD) persists as a major cause of morbidity and mortality in the United States, with more than 40% of all deaths each year directly attributed to the disease. Dyslipidemia is recognized as a major risk factor for the development and progression of CHD, with clinical trials clearly demonstrating the public health and economic benefits of favorable cholesterol modification. As a result of this evidence, the National Cholesterol Education Program (NCEP) has developed guidelines for the detection, evaluation, and treatment of high blood cholesterol in adults. The most recent of the NCEP recommendations, the Adult Treatment Panel III (ATP III) guidelines, were released in May 2001 and build on the earlier editions and reiterate the importance of low-density lipoprotein cholesterol (LDL-C) reduction to modify CHD risk. New features of the guidelines include the identification of CHD risk equivalents; lower treatment target goals; an emphasis on conditions conferring a higher risk for CHD, such as the metabolic syndrome; and a scoring system for calculating CHD risk. The ATP III emphasis on risk assessment will result in a substantial increase in the number of patients considered at risk for CHD and will expand the number eligible for lifestyle and drug intervention. |
| The national cholesterol education program adult treatment panel ill guidelines Clearfield, M. B. (2003), J Am Osteopath Assoc 103(1 Suppl 1): S1-5. Abstract: Coronary heart disease (CHD) remains the leading cause of death in the United States with more than 40% of all deaths each year directly attributed to the disease. Current evidence suggests that early identification and aggressive modification of risk factors offer the most promising approach to reducing the burden of CHD. Dyslipidemia has been identified as the primary risk factor leading to the development of CHD. It is estimated that nearly 65 million Americans require some form of lipid-modification therapy. The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) set of guidelines released in May 2001 provides physicians with evidence-based recommendations on the classification, diagnosis, and treatment of lipid disorders. New features of the guidelines include a scoring system for calculating CHD risk, as well as the identification of CHD risk equivalents, lower treatment target goals, and an emphasis on conditions conferring a higher risk for CHD, such as the metabolic syndrome. The ATP III emphasis on risk assessment substantially increases the number of patients considered at risk for CHD and will expand the number eligible for lifestyle and drug interventions. This article highlights the new recommendations and reviews the impact of ATP III on osteopathic physicians. |
| The national cholesterol education program diet vs a diet lower in carbohydrates and higher in protein and monounsaturated fat: a randomized trial Aude, Y. W., A. S. Agatston, et al. (2004), Arch Intern Med 164(19): 2141-6. Abstract: BACKGROUND: In the United States, obesity is a major clinical and public health problem causing diabetes, dyslipidemia, and hypertension, as well as increasing cardiovascular and total mortality. Dietary restrictions of calories and saturated fat are beneficial. However, it remains unclear whether replacement of saturated fat with carbohydrates (as in the US National Cholesterol Education Program NCEP diet) or protein and monounsaturated fat (as in our isocaloric modified low-carbohydrate MLC diet, which is lower in total carbohydrates but higher in protein, monounsaturated fat, and complex carbohydrates) is optimal. METHODS: We randomized 60 participants (29 women and 31 men) to the NCEP or the MLC diet and evaluated them every 2 weeks for 12 weeks. They were aged 28 to 71 years (mean age, 44 years in the NCEP and 46 years in the MLC group). A total of 36% of participants from the NCEP group and 35% from the MLC group had a body mass index (calculated as weight in kilograms divided by the square of height in meters) greater than 27. The primary end point was weight loss, and secondary end points were blood lipid levels and waist-to-hip ratio. RESULTS: Weight loss was significantly greater in the MLC (13.6 lb) than in the NCEP group (7.5 lb), a difference of 6.1 lb (P =.02). There were no significant differences between the groups for total, low density, and high-density lipoprotein cholesterol, triglycerides, or the proportion of small, dense low-density lipoprotein particles. There were significantly favorable changes in all lipid levels within the MLC but not within the NCEP group. Waist-to-hip ratio was not significantly reduced between the groups (P =.27), but it significantly decreased within the MLC group (P =.009). CONCLUSIONS: Compared with the NCEP diet, the MLC diet, which is lower in total carbohydrates but higher in complex carbohydrates, protein, and monounsaturated fat, caused significantly greater weight loss over 12 weeks. There were no significant differences between the groups in blood lipid levels, but favorable changes were observed within the MLC diet group. |
| The National Cholesterol Education Program pediatric guidelines: behavioral considerations Rosenthal, S. L., S. Knauer-Black, et al. (1992), J Dev Behav Pediatr 13(4): 288-9. |
| The National Cholesterol Education Program: guidelines, status, and issues Goodman, D. S. (1991), Am J Med 90(2A): 32S-35S. Abstract: The 1987 report of the Adult Treatment Panel (ATP) of the National Cholesterol Education Program (NCEP) was concerned with who should be treated for high blood cholesterol levels and how they should be treated. Total cholesterol levels were classified for identification of cases. Low-density lipoprotein cholesterol levels were classified for decisions about treatment. The ATP guidelines emphasize diet as the primary approach to treating patients with high blood cholesterol levels. The recommendations of the report are being widely publicized through physician and patient educational programs and the mass media. The report of the Population Panel of the NCEP provides recommendations and guidelines for the public health approach to the problem of high cholesterol levels. When the recommendations of both reports are fully implemented, it is expected that substantial reductions in the incidence of coronary heart disease will be achieved. |
| The National Cholesterol Education Program: progress and prospects Cleeman, J. I. and C. Lenfant (1998), Jama 280(24): 2099-104. Abstract: The National Cholesterol Education Program (NCEP) is a prime example of the role the National Heart, Lung, and Blood Institute has played, in its 50 years of existence, as a catalyst for translating research advances into improved clinical and public health practices. Since its inception in 1985, the NCEP has adhered to 2 principles in mounting educational campaigns for professionals and the public: building on a strong science base and working in partnership with other organizations. In slightly more than a decade, the NCEP has made significant progress toward its goal of reducing the prevalence of high blood cholesterol. The impact of cholesterol education is clearly visible in 4 major trends: increasing professional and public cholesterol awareness; declining dietary intakes of saturated fat, total fat, and cholesterol; falling serum cholesterol levels; and a continuing decline in coronary heart disease (CHD) mortality rates. Nevertheless, cholesterol levels are still being undertreated, especially in patients with CHD, and substantial scientific and educational challenges remain. As it looks forward to the 21st century, the NCEP plans to make continued progress by using emerging scientific developments and pursuing the powerful combination of cholesterol lowering in CHD patients and in primary prevention. |
| The natural history of coronary disease. The role of cholesterol Ovize, M., M. de Lorgeril, et al. (1990), Ann Cardiol Angeiol (Paris) 39(5): 295-300. Abstract: The natural history of the complications of coronary heart disease has been defined by anatomicopathological and epidemiological studies, particularly the Framingham study. At the same time, research is being carried out on risk factors which play a role in the progressive development of atheromatous plaque (atherogenic factors: hypertension: hypercholesterolaemia) and those factors which lead to complications in the atheromatous plaque (aggravating or precipitating factors: smoking, thrombosis, etc.). This schematic perspective may lead to the redefinition of the strategy to adopt in fighting atherosclerotic arterial disease; a better aim will thus the taken in the fight against hypercholesterolaemia. |
| The nature of the conductance increase induced by filipin in cholesterol-containing planar lipid bilayers Krawczyk, J. and S. Cukierman (1991), Biochim Biophys Acta 1063(1): 60-6. Abstract: The effects of the polyene antibiotic filipin on the conductance and permeability of planar lipid bilayers were investigated under voltage-clamp conditions. The membrane conductance of lipid bilayers containing no cholesterol was not affected by filipin. In the presence of cholesterol containing lipid bilayers, filipin induced a 10(4)-10(5)-fold increase in transmembrane conductance. This conductance increase was dependent on the ionic species present in solution, decreasing in the following order: GCsCl greater than GNaAc greater than GKCl greater than GNaCl greater than CaCl2 greater than GNa2SO4 greater than GBaCl2 greater than GMgCl2. Reversal potential measurements in simple biionic conditions revealed the following relative permeability sequence: PK greater than PCl greater than PNa approximately Pac approximately PBa greater than PCs greater than PMg approximately PCa greater than Psulphate. The filipin-sterol mediated increase in membrane conductance was independent of the membrane potential. The increase in membrane current following a step alteration in membrane potential occurred instantaneously and had no dependence on the previous value of the holding membrane potential. We propose that the filipin-sterol complex forms ion channels in lipid membranes. These channels are found in a single configuration (open state) and select preferentially monovalent cations or anions over divalent ions. Our experimental results are discussed in relation to the effects of other polyene antibiotics on the membrane permeability, and also in relation to experimental problems previously reported with the use of filipin in planar lipid bilayers. |
| The need for a different cholesterol lowering drug Steiner, G. (2003), Can J Clin Pharmacol 10 Suppl A: 4A-6A. |
| The neurodegeneration mutant lochrig interferes with cholesterol homeostasis and Appl processing Tschape, J. A., C. Hammerschmied, et al. (2002), Embo J 21(23): 6367-76. Abstract: The novel Drosophila mutant lochrig (loe) shows progressive neurodegeneration and neuronal cell death, in addition to a low level of cholesterol ester. loe affects a specific isoform of the gamma-subunit of AMP-activated protein kinase (AMPK), a negative regulator of hydroxymethylglutaryl (HMG)-CoA reductase and cholesterol synthesis in vertebrates. Although Drosophila cannot synthesize cholesterol de novo, the regulatory role of fly AMPK on HMG-CoA reductase is conserved. The loe phenotype is modified by the level of HMG-CoA reductase and suppressed by the inhibition of this enzyme by statin, which has been used for the treatment of Alzheimer patients. In addition, the degenerative phenotype of loe is enhanced by a mutation in amyloid precursor protein-like (APPL), the fly homolog of the human amyloid precursor protein involved in Alzheimer's disease. Western analysis revealed that the loe mutation reduces APPL processing, whereas overexpression of Loe increases it. These results describe a novel function of AMPK in neurodegeneration and APPL/APP processing which could be mediated through HMG-CoA reductase and cholesterol ester. |
| The new atherogenic plasma index reflects the triglyceride and HDL-cholesterol ratio, the lipoprotein particle size and the cholesterol esterification rate: changes during lipanor therapy Dobiasova, M. and J. Frohlich (2000), Vnitr Lek 46(3): 152-6. Abstract: The new atherogenic plasma index (AIP) is a logarithmic transformation of the ratio of the molar triglyceride (TG) concentration and high density lipoprotein cholesterol (HDL-C). AIP correlates closely with the size of LDL particles (r = 0.8) and esterification rate of plasma cholesterol devoid of apo B lipoproteins (FERHDL), r = 0.9 which are considered at present the most sensitive indicators of the atherogenic plasma profile. AIP was recommended by the authors, based on analysis of results of 11 previous studies (1156 subjects) where FERHDL and plasma lipid parameters were investigated in different groups of people who differed as to the atherogenic risk. The AIP index was moreover used for evaluation of a clinical study comprising 609 patients with hyperlipidaemia, who were treated for three months with ciprofibrate (Lipanor). The mean AIP values of non-risk groups (plasma from umbilical blood, children, healthy women etc.) equalled zero or were lower, while with an increasing atherogenic risk (men, women after the menopause) AIP reached positive values, incl. high positive values in risk groups (plasma of diabetic subjects, patients with HLP, patients with positive angiography, myocardial infarction etc.). In all groups women had lower AIP values as compared with males. In patients after Lipanor therapy the AIP declined (from 0.58 +/- 0.17 to 0.33_0.18 in men, from 0.50 +/- 0.18 to 0.21 +/- 0.19 in women). If we consider AIP values from negative ones to 0.15 as "safe" from the aspect of atherogenicity, before Lipanor treatment these "safe" levels were recorded in 1.5% men and in 5.2% women and after treatment in 32% men and 48% women. The results indicate, that AIP which reflects the plasma lipoprotein profile quantifies the relations between TG and HDL-C and thus can be an objective indicator of the atherogenic risk and effectiveness of treatment and it is useful because it can be assessed in any surgery. |
| The new cholesterol guidelines. Applying them in clinical practice Pearlman, B. L. (2002), Postgrad Med 112(2): 13-6, 19-22, 25-6 passim. Abstract: In 2001, the National Institutes of Health released the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Compared with previous cholesterol guidelines, the new guidelines contain several significant changes in treatment recommendations for patients with hyperlipidemia. In this article, Dr Pearlman reviews the latest guidelines and offers case examples that demonstrate how to incorporate the recommendations routinely into clinical practice. |
| The new debate on cholesterol: is the lowest level the best? Olsson, A. G. (1999), Lakartidningen 96(6): 648-52. |
| The Niemann-Pick C lesion and its relationship to the intracellular distribution and utilization of LDL cholesterol Pentchev, P. G., R. O. Brady, et al. (1994), Biochim Biophys Acta 1225(3): 235-43. |
| The Niemann-Pick C proteins and trafficking of cholesterol through the late endosomal/lysosomal system Garver, W. S. and R. A. Heidenreich (2002), Curr Mol Med 2(5): 485-505. Abstract: To maintain proper cellular function, the amount and distribution of cholesterol residing within cellular membranes must be regulated. The principal disorder affecting transport of cholesterol through the late endosomal/lysosomal system and intracellular cholesterol homeostasis is Niemann-Pick type C (NPC) disease. The genes responsible for NPC disease have been identified, and the encoded Niemann-Pick C1 (NPC1) and Niemann-Pick C2 (HE1/NPC2) proteins are currently the subject of intense investigation. This review provides a detailed examination of NPC1 and HE1/NPC2 in regulating the transport of cholesterol through the late endosomal/lysosomal system to other cellular compartments responsible for maintaining intracellular cholesterol homeostasis, and how defective function of these proteins may be responsible for the pathophysiology associated with NPC disease. |
| The niemann-pick disease genes; regulators of cellular cholesterol homeostasis Ory, D. S. (2004), Trends Cardiovasc Med 14(2): 66-72. Abstract: Cellular cholesterol homeostasis is maintained through activation of the designated sterol regulatory element binding proteins and liver X receptor transcriptional pathways. Insight into the molecular mechanisms that regulate these pathways has come from the study of Niemann-Pick C (NPC) disease. Mutations in the NPC1 and NPC2 disease genes lead to lysosomal accumulation of cholesterol and defects in regulation of sterol homeostatic responses. NPC1 and NPC2 are key participants in intracellular cholesterol trafficking and are required for production of low-density lipoprotein cholesterol-derived oxysterols. In this review, the function of NPC1 and NPC2 in sterol trafficking and regulation of cholesterol homeostasis is examined. Study of the NPC proteins will further understanding of the mechanisms involved in atherogenesis. |
| The nonlinearity seen for LDL-cholesterol with lyophilized material is a matrix effect Kroll, M. H. and R. Chesler (1998), Clin Chem 44(8 Pt 1): 1770-1. |