| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| The LDL receptor gene family, apolipoprotein B and cholesterol in embryonic development Herz, J. and R. V. Farese, Jr. (1999), J Nutr 129(2S Suppl): 473S-475S. Abstract: In recent years, a number of genes that are involved in cholesterol synthesis, its systemic or intercellular transport or lipid metabolism in general have been found to play important roles during embryonic development. In this article, we present a brief overview of these genes, their molecular functions as we understand them to date and our current interpretation of possible mechanisms by which genetic deficiency states might affect the development of the embryo, in particular the formation of the central nervous system. |
| The level of triglycerides, total cholesterol and HDL cholesterol in various stages of human immunodeficiency virus (HIV) infection Rogowska-Szadkowska, D. and A. Borzuchowska (1999), Pol Arch Med Wewn 101(2): 145-50. Abstract: In 63 HIV-infected individuals the levels of concentration plasma triglicerides, total cholesterol and HDL cholesterol were determined by the level of immunological deficiency defined according to the CD4 lymphocytes count. The analyzed markers of lipid disorder allow to draw the following conclusions: 1. Along with the increase of immunological deficiency and clinical development of the HIV infection the disorders, which are indicated by the increase in trigliceride levels and decreased plasma concentrations for HDL cholesterol, intensify as well. 2. HIV-infected persons, particularly those treated with protease inhibitors, should have carefully monitored lipid metabolism. |
| The levels of soluble amyloid beta in different high density lipoprotein subfractions distinguish Alzheimer's and normal aging cerebrospinal fluid: implication for brain cholesterol pathology? Koudinov, A. R., T. T. Berezov, et al. (2001), Neurosci Lett 314(3): 115-8. Abstract: Several previous studies reported the association of the soluble form of amyloid beta (sA beta) protein, a major constituent of amyloid deposits in Alzheimer's disease (AD), with normal blood, cerebrospinal fluid (CSF) and central nervous system high density lipoproteins (HDLs). The present report aimed to elucidate the pattern of sA beta and apolipoprotein (apo) distribution in AD CSF-HDL subfractions. We studied AD CSF-HDL subfractions by SDS/PAGE and immunoblot analysis after CSF fractionation via density flotation ultracentrifugation. AD CSF was characterized by (i) increased sA beta and apo content of the HDL(1), and (ii) sA beta association with apoE and apoJ in HDL(2), HDL(3) and very high density lipoproteins. The finding supports our proposed hypothesis that upregulation of brain cholesterol dynamics is a fundamental event in the pathophysiology of AD and that sA beta binding to apo and lipid may have important structure-functional consequences. |
| The link between serum cholesterol and diet Goo, C. H. (2003), J Hum Nutr Diet 16(3): 189-90; author reply 191. |
| The linoleic acid content of test diets must be carefully monitored in cholesterol studies Hayes, K. C. (1997), Am J Clin Nutr 65(4): 1087-8. |
| The lipid treatment assessment project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals Pearson, T. A., I. Laurora, et al. (2000), Arch Intern Med 160(4): 459-67. Abstract: OBJECTIVE: To determine the percentage of patients in the multicenter Lipid Treatment Assessment Project receiving lipid-lowering therapy who are achieving low-density lipoprotein cholesterol (LDL-C) goals as defined by National Cholesterol Education Program (NCEP) guidelines. METHODS: Adult patients with dyslipidemia, who had been receiving the same lipid-lowering therapy for at least 3 months, were assessed at investigation sites. Lipid levels were determined once in each patient at the time of enrollment. The primary end point was the success rate, defined as the proportion of patients who achieved their LDL-C target level as specified by NCEP guidelines. RESULTS: A total of 4888 patients from 5 regions of the United States were studied. Of these, 23% had fewer than 2 risk factors for coronary heart disease (CHD) and no evidence of CHD (low-risk group), 47% had 2 or more risk factors and no evidence of CHD (high-risk group), and 30% had established CHD. Overall, only 38% of patients achieved NCEP-specified LDL-C target levels; success rates were 68% among low-risk patients, 37% among high-risk patents, and 18% among patients with CHD. Drug therapy was significantly (P< or =.001) more effective than nondrug therapy in all patient risk groups. However, many patients treated with lipid-lowering drugs did not achieve LDL-C target levels. CONCLUSIONS: Large proportions of dyslipidemic patients receiving lipid-lowering therapy are not achieving NCEP LDL-C target levels. These findings indicate that more aggressive treatment of dyslipidemia is needed to attain goals established by NCEP guidelines. |
| The lipid-protein indices of the blood cholesterol transport system in systemic lupus erythematosus Alekberova, Z. S., T. V. Popkova, et al. (1999), Ter Arkh 71(5): 34-8. Abstract: AIM: To assess parameters of blood cholesterol lipid-protein spectrum and characteristics of blood cholesterol (C) transport system in patients with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: Lipid-protein blood spectrum was studied in 60 patients (45 females and 15 males) with verified SLE aged 15-44 years (mean age 28.9 +/- 8.1 years). The duration of the disease varied from 2 months to 28 years (mean 8.6 +/- 6.6 years). SLE course and activity were defined according to V. A. Nasonova's classification. The control patients (35 healthy subjects) were matched by age (30.0 +/- 6.1 years) and gender (27 females and 8 males). RESULTS: Elevated levels of C and C of low-density lipoproteins (LDLP), triglycerides (TG) were found in 35% and 30% of patients, respectively. C of high-density lipoproteins (HDLP) was low in 32% of patients. HDLP phospholipids were also subnormal, their proportion changed: concentrations of phosphatidylcholine were low, those of lisophosphatidylcholine, sphingomyelin, diethanolamine, cardiolipin were higher than in the controls. TG and proportion apo/B/AI were higher, content of HDLP components low in patients with the disease duration up to 5 years. Patients with highly and moderately active SLE had high levels of TG, apo/B, apo/B/apo/AI, low levels of HDLP C, apo/AI and HDLP phospholipids. CONCLUSION: Marked dyslipidemias were detected in 1/3 of SLE patients. Cholesterol transport changes arise at early SLE stages. Alterations in the blood lipid-protein spectrum appeared more pronounced and atherogenic in maximal SLE activity. Quantitative and qualitative shifts in HDLP composition induce changes in antiatherogenic properties of relevant lipoproteins in SLE patients. |
| The lipoprotein lipase HindIII polymorphism: association with total cholesterol and LDL-cholesterol, but not with HDL and triglycerides in 342 females Larson, I., M. M. Hoffmann, et al. (1999), Clin Chem 45(7): 963-8. Abstract: BACKGROUND: Lipoprotein lipase (LPL) is the rate-limiting enzyme in the hydrolysis of core triglycerides in chylomicrons and VLDL. METHODS: We investigated the association between the HindIII polymorphism of the LPL gene and fasting glucose, lipid, and lipoprotein concentrations in 683 Caucasians. We first stabilized the study subjects, using an 8-day diet and exercise intervention program before obtaining blood samples. The use of this standardization period reduced the variance of all glucose and lipid concentrations. RESULTS: In our study, the HindIII allele frequencies for females and males were 0.29 and 0.34 for H- and 0.71 and 0.66 for H+, respectively. We found in females, but not in males, a significant association between the HindIII genotype and total cholesterol (P = 0.007) and LDL-cholesterol (P = 0.018), with females homozygous for the rare H- allele having the lowest, heterozygotes (H-/+) having intermediate, and women homozygous for the common H+ allele having the highest of each of these lipid traits. With regard to triglycerides, HDL-cholesterol, and glucose, no significant effect of the HindIII genotype was noted in either gender. CONCLUSIONS: These results suggest that in a gender-specific manner, the rare LPL HindIII H- allele has a cholesterol-lowering and, therefore, potentially cardioprotective effect compared with the common H+ allele. |
| The liver metabolite S-422 of the hypolipidaemic drug benfluorex decreases cholesterol esterification in fibroblasts and monocyte-like cells Maziere, J. C., C. Maziere, et al. (1991), Eur J Clin Pharmacol 41(4): 339-44. Abstract: The effects of S-422 (1-(3-trifluoromethylphenyl)-2-N-(2-hydroxyethyl) amino propane), an hepatic metabolite of the hypolipidaemic drug Benfluorex, on lipid metabolism have been investigated in two experimental models: in human fetal lung fibroblasts, for study of the apo B/E receptor-mediated regulation of cholesterol metabolism, and in murine J 774 monocyte-like cells, for study of the scavenger receptor-mediated induction of cholesteryl ester accumulation. In human fibroblasts S-422 increased low density lipoprotein (LDL) catabolism by about 20%, whereas it decreased oleic acid incorporation into triacylglycerols and cholesteryl esters by 25 and 35%, respectively. In J 774 cells, S-422 decreased acetylated LDL degradation and cholesteryl ester formation by about 35%. In both cell types, ACAT activity was significantly reduced by the drug, either after a 24 h pretreatment of the cultured cells, or after an in vitro 30 min preincubation of cell homogenates. The results suggest that S-422, and thus Benfluorex, might prevent the development of atherosclerotic plaques. |
| The liver X receptor-{beta} is essential for maintaining cholesterol homeostasis in the testis Robertson, K. M., G. U. Schuster, et al. (2005), Endocrinology 146(6): 2519-30. Abstract: The liver X receptor (LXR)alpha and -beta has been found to play a central role in maintaining cellular cholesterol homeostasis. In this study we comprehensively investigated the effect of deleting LXRalpha and -beta on testicular morphology and function. In the absence of LXRbeta, excessive cholesterol accumulated in the Sertoli cells from 2.5 months, resulting in severe cellular disruption and dysregulation of spermatogenesis by 10 months of age. This correlated with gene expression analyses that clearly indicated that LXRbeta was the dominant transcript in the testis Although the LXRalpha(-/-) testis was normal, the LXRalpha(-/-)beta(-/-) testis presented with a more severe phenotype than the LXRbeta(-/-) mice, and males were infertile by 4 months of age, indicating LXRalpha may partially rescue the testicular phenotype. Although Leydig cells did not accumulate excessive cholesterol, declining serum and intratesticular androgen levels with age suggested that these cells were in fact less functional. Treatment of a Sertoli cell line with the LXR agonist T0901317 led to increased expression of known LXR target genes like ATP binding cassette-G1 and sterol regulatory binding protein-1c; similar results were observed in wild-type testis after in vivo administration, suggesting the LXR is functioning in the same way as in other tissues. Ordinarily increased levels of cholesterol activate intracellular sensors to decrease these levels; however, the increasing amount of cholesterol in the Sertoli cells indicates improper control of cholesterol metabolism when LXRbeta is absent. Although the precise molecular mechanism at this time remains unclear, our study highlights the crucial role for LXRbeta in retaining cholesterol homeostasis in Sertoli cells. |
| The long-term follow-up of drainage procedures for petrous apex cholesterol granulomas Fong, B. P., D. E. Brackmann, et al. (1995), Arch Otolaryngol Head Neck Surg 121(4): 426-30. Abstract: OBJECTIVE: To determine the long-term effectiveness of various approaches to surgical drainage of petrous apex cholesterol granulomas. DESIGN: A retrospective cohort study in which patients treated by surgical drainage for petrous apex cholesterol granulomas were followed up for a minimum of 1 year (mean, 4.6 years). SETTING: House Ear Clinic, an otologic tertiary care center in Los Angeles, Calif. PATIENTS: A total of 25 patients who underwent either transcanal infracochlear, infralabyrinthine, middle fossa, or translabyrinthine drainage and who had at least 1 year of clinical and, in some cases, radiologic postoperative follow-up. MAIN OUTCOME MEASURES: Relief or recurrence of symptoms, need for revision surgery, postoperative hearing, appearance on postoperative imaging studies. RESULTS: Twenty-three patients had improvement or complete resolution of preoperative noncranial nerve VIII nerve dysfunction. Hearing was preserved in cases of middle fossa, infralabyrinthine, and infracochlear approaches with serviceable preoperative hearing. Hearing did not improve in cases of total preoperative hearing loss. Of the patients who underwent postoperative imaging, over three fourths had reduction in lesion size and one third developed aeration of the petrous apex. Revision surgery was required in three patients. Recently developed, the infracochlear approach has shown excellent early results. Lesion size was reduced in five of five patients, and the petrous apex contained air in three of five patients who underwent the infracochlear approach. CONCLUSION: Drainage via the infracochlear and infralabyrinthine approaches offers effective long-term decompression of petrous apex cholesterol granulomas, while preserving hearing. |
| The low cholesterol-mortality association in a national cohort Harris, T., J. J. Feldman, et al. (1992), J Clin Epidemiol 45(6): 595-601. Abstract: The relationship of low serum cholesterol and mortality was examined in data from the NHANES I Epidemiologic Followup Study (NHEFS) for 10,295 persons aged 35-74, 5833 women with 1281 deaths and 4462 men with 1748 deaths (mean (followup = 14.1 years). Serum cholesterol below 4.1 mmol/l was associated with increased risk of death in comparison with serum cholesterol of 4.1-5.1 mmol/l (relative risk (RR) for women = 1.7, 95% confidence interval (CI) = (1.2, 2.3); for men RR = 1.4, CI = (1.1, 1.7)). However, the low serum cholesterol-mortality relationship was modified by time, age, and among older persons, activity level. The low serum cholesterol-mortality association was strongest in the first 10 years of followup. Moreover, this relationship occurred primarily among older persons (RR for low serum cholesterol for women 35-59 = 1.0 (0.6, 1.8), for women 70-74, RR = 2.1 (1.2, 3.7); RR for low serum cholesterol for men 35-59 = 1.2 (0.8, 2.0), for men 70-74, RR = 1.9 (1.3, 2.7)). Among older persons, however, the low serum cholesterol-mortality association was confined only to those with low activity at baseline. Factors related to underlying health status, rather than a mortality-enhancing effect of low cholesterol, likely accounts for the excess risk of death among persons with low cholesterol. The observed low cholesterol-mortality association therefore should not discourage public health programs directed at lowering serum cholesterol. |
| The low fat/low cholesterol diet Baschetti, R. (1997), Eur Heart J 18(9): 1514-5. |
| The low fat/low cholesterol diet is ineffective Corr, L. A. and M. F. Oliver (1997), Eur Heart J 18(1): 18-22. |
| The low HDL cholesterol/high triglyceride trait Sprecher, D. L., H. S. Feigelson, et al. (1993), Arterioscler Thromb 13(4): 495-504. Abstract: In 748 probands and 3,283 first-degree relatives from the Collaborative Lipid Research Clinics (LRC) Family Study, our specific aim was to examine the degree to which low (bottom decile) high density lipoprotein cholesterol (HDL-C, hypoalpha) and high (top decile) triglyceride (TG, hyperTG) levels occur conjointly (CT) and the extent to which these characteristics were shared within families. To control for family size and permit a comparison with the proband percentages, mean familial percentages of HDL-C/TG abnormalities were calculated. Concurrent low HDL-C and high TG levels were present in 2.7% of the probands, a value that was enriched to 12.7% (p = 0.003) of their associated first-degree relatives. If the proband had a low HDL-C value, 7.7% (p = 0.013) of relatives had CT. Familial (proband and at least one first-degree family member share the same lipoprotein/lipid phenotype) hypoalpha was observed in 2.4% of families while familial hyperTG was observed in 4.1%. Familial CT was seen in approximately 0.7%. If the proband had CT, 80% of their families had at least one other first-degree member with an HDL-C/TG abnormality, whereas the corresponding percentage for families associated with probands with only hypoalpha was 64% and for those with hyperTG alone, 54%. A broadly shared environmental factor cannot easily explain the familial association of hypoalpha, hyperTG, and CT. In probands with low HDL-C values alone or the conjoint low-HDL-C/high-TG trait, family screening is extremely valuable because low HDL-C/high TG is enriched in the respective family members, a conjoined trait closely associated with increased coronary heart disease risk. |
| The low-density lipoprotein cholesterol-lowering effect of pravastatin and factors associated with achieving targeted low-density lipoprotein levels in an African-American population Chong, P. H., P. J. Tzallas-Pontikes, et al. (2000), Pharmacotherapy 20(12): 1454-63. Abstract: STUDY OBJECTIVES: To describe the low-density lipoprotein cholesterol (LDL)-lowering effect of pravastatin in African-American patients and to identify factors associated with achieving National Cholesterol Education Program (NCEP)-defined target levels. DESIGN: Retrospectively defined cohort study. SETTING: Large, government-owned, teaching hospital. PATIENTS: Eighty-four African-American patients starting therapy with pravastatin in October-November 1997. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Whether or not target LDL concentrations were achieved was used to measure efficacy. Stepwise logistic regression identified the target LDL, baseline LDL, and baseline high-density lipoprotein cholesterol (HDL) as significant predictors of achieving the target. The proportion of patients achieving their target LDL when that target was below 160, below 130, and 100 mg/dl or below was 64%, 32%, and 13% (p=0.004), respectively. Medical record review identified the reasons for not achieving target as incorrect drug regimen, inadequate lipid monitoring, and noncompliance. CONCLUSION: These results indicate that substantial numbers of patients receiving lipid-lowering therapy are not meeting NCEP-defined targets and that with increased drug monitoring and compliance, improvements in achieving NCEP target LDL levels could be realized. |
| The low-density lipoprotein receptor and cholesterol synthesis are affected differently by dietary cholesterol in the rat Roach, P. D., S. Balasubramaniam, et al. (1993), Biochim Biophys Acta 1170(2): 165-72. Abstract: In the hamster and the rabbit, the low-density lipoprotein (LDL) receptor and cholesterol synthesis are coordinately downregulated by dietary cholesterol. In the rat, cholesterol synthesis is downregulated but LDL kinetic studies suggest that the LDL receptor is not. The aim of this study was to determine the effect of dietary cholesterol on the expression of the hepatic LDL receptor in the rat. Young (2 months) hooded and albino Wistar rats and older (9 months) Sprague-Dawley rats were used because of their reported different propensities to develop hypercholesterolaemia when fed cholesterol. Hepatic LDL receptor activity was measured using a dot blot assay with LDL-gold and LDL receptor mass was measured using an electroblot assay with a polyclonal antibody. Dietary cholesterol had no effect on the plasma cholesterol concentration in both strains of young Wistar rats but increased it in the older Sprague-Dawley rats. Cholesterol synthesis as measured with 3H2O or as indicated by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity or the ratio of plasma lathosterol to cholesterol was effectively downregulated by dietary cholesterol (1% w/w) in all three strains. In contrast, dietary cholesterol increased both hepatic LDL receptor activity and mass in the young Wistar rats and had no effect on either receptor activity or mass in the older Sprague-Dawley rats. Increases in receptor activity occurred despite increases in hepatic cholesterol especially when cholic acid was added to the cholesterol diet. The effect was systemic because CL 277082, an inhibitor of intestinal cholesterol absorption, prevented the increase in LDL receptor activity.(ABSTRACT TRUNCATED AT 250 WORDS) |
| The lower LDL cholesterol the better! Stenestrand, U. and A. G. Olsson (2004), Lakartidningen 101(42): 3246-7. |
| The lower the better? Reviewing the evidence for more aggressive cholesterol reduction and goal attainment Stein, E. (2002), Atheroscler Suppl 2(4): 19-23; discussion 23-5. Abstract: There is considerable evidence that more aggressive lowering of low-density lipoprotein (LDL) cholesterol is associated with increased benefits in reducing atherosclerotic disease burden, supporting the notion of 'the lower, the better.' However, achievement of currently recommended goals has proven difficult with lipid-lowering agents at the commonly used doses. Current options for achieving greater LDL cholesterol reductions include use of high doses of the most effective of the available statins and use of high or moderate statin doses in combination with agents that work in a complementary manner (e.g. bile acid sequestrants or niacin). Near-term options may include statins with increased LDL cholesterol-lowering effectiveness and better-tolerated secondary agents that can be combined with statin therapy. Rosuvastatin (Crestor, AstraZeneca) is a new statin that may prove to be of considerable utility in achieving greater LDL cholesterol reductions than are currently possible with existing statins. Recent phase III clinical trials have shown that this agent produces significantly greater LDL cholesterol reductions than atorvastatin, simvastatin, or pravastatin in patients with primary hypercholesterolemia and significantly greater reductions than the maximal dose of atorvastatin in patients with familial hypercholesterolemia. |
| The lymphatic absorption of dihydrolanosterol and cholesterol in the rat Satchithanandam, S., L. L. Gallo, et al. (1999), Res Commun Mol Pathol Pharmacol 103(1): 91-100. Abstract: Dihydrolanosterol (DHL) and its analogs have been studied extensively as cholesterol biosynthesis inhibitors. They inhibit specific steps in cholesterol synthesis by inhibiting lanosterol demethylase and by suppressing HMG-CoA reductase. The present study was designed to estimate the lymphatic absorption of DHL. For comparison, a cholesterol group was included. The left thoracic duct of male Wistar rats weighing between 210 and 230 g was cannulated. A lipid emulsion containing 0.75microCi of either 3H-DHL or 3H-cholesterol was given intragastrically. After the lipid meal, lymph was collected at 3 h intervals up to 9 h and then at 24 h. Radioactivity of DHL and cholesterol in the lymph was estimated. Lipid extracts of lymph specimens were also subjected to thin layer chromatography and fractions of DHL, cholesterol and their esters were isolated and the masses were estimated. There were no differences in lymph volumes between the two groups. However, absorption and esterification of DHL in lymph were significantly reduced compared with the cholesterol group. The marked decrease in the esterification of DHL is likely due to its poor absorption into the mucosal cell and subsequently into the lymphatic system. The amount of DHL available in the mucosal cell for esterification may be a limiting factor. |