| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Understanding the basis for variation in response to cholesterol-lowering diets Krauss, R. M. (1997), Am J Clin Nutr 65(3): 885-6. |
| Understanding the biological activity of amyloid proteins in vitro: from inhibited cellular MTT reduction to altered cellular cholesterol homeostatis Liu, Y. (1999), Prog Neuropsychopharmacol Biol Psychiatry 23(3): 377-95. Abstract: 1. MTT is taken into the cell through endocytosis and is reduced and accumulated in a population of acidic vesicles. Reduced MTT formazan is exocytosed to form needle-like formazan crystals at the cell surface. Mitochondria are unlikely to play a significant role in cellular MTT reduction. 2. Amyloid fibrils inhibit cellular MTT reduction indirectly by enhancing MTT formazan exocytosis. All protein fibrils with beta-pleated sheet structure which have been examined enhance MTT formazan exocytosis and induce neurotoxicity. 3. Cellular free cholesterol regulates the exocytosis of the intracellular MTT formazan-transporting vesicles and these vesicles may be involved in cellular cholesterol homeostasis. 4. Amyloid fibrils inhibit cholesterol esterification and alter the distribution of free cholesterol in neurons. 5. Amyloid fibril-induced alterations in cellular cholesterol metabolism and vesicle trafficking may contribute to neurodegeneration in vivo. |
| Understanding the cholesterol transport system Porth, C. M. (1995), Nursing 25(4): 32T-32U. |
| Understanding the mechanism of LCAT reaction may help to explain the high predictive value of LDL/HDL cholesterol ratio Dobiasova, M. and J. Frohlich (1998), Physiol Res 47(6): 387-97. Abstract: Traditionally, lecithin:cholesterol acyltransferase (LCAT) role in the reverse cholesterol transport (RCT) has been considered "antiatherogenic" as the cholesterol esterification is the prerequisite for the formation of mature high density lipoprotein (HDL) particles and may create a gradient necessary for the flow of unesterified cholesterol (UC) from tissues to plasma. However, newer data suggest that a higher esterification rate is not necessarily protective. Here we review the available data on the role of LCAT in RCT and propose that the LCAT-mediated esterification of plasma cholesterol promotes RCT only in the presence of sufficient concentrations of HDL2 while this reaction may be atherogenic in the presence of high concentration of plasma low density lipoprotein (LDL) cholesterol Thus, the "protective" or potentially "atherogenic" role of LCAT depends on the quality of HDL and concentration of LDL. This hypothesis is consistent with the known high predictive value of LDL/HDL cholesterol ratio. |
| Underutilization of lipid-lowering drugs in older persons with prior myocardial infarction and a serum low-density lipoprotein cholesterol > 125 mg/dl Aronow, W. S. (1998), Am J Cardiol 82(5): 668-9, A6, A8. Abstract: A prospective study of 500 consecutive persons (aged 60 years with Q-wave myocardial infarction admitted to a long-term health care facility) investigated the prevalence of the use of a lipid-lowering drug at the time of admission in persons with a fasting serum low-density lipoprotein (LDL) cholesterol >125 mg/dl measured the day after admission. The prevalence of a lipid-lowering drug in persons with myocardial infarction and an LDL cholesterol >125 mg/dl was 7% (11 of 153 persons) in persons 60 to 80 years of age and 3% (6 of 182 persons) in persons 81 to 100 years of age. |
| Underutilization of measurement of serum low-density lipoprotein cholesterol levels and of lipid-lowering therapy in older patients with manifest atherosclerotic disease Mendelson, G. and W. S. Aronow (1998), J Am Geriatr Soc 46(9): 1128-31. Abstract: OBJECTIVE: To investigate the prevalence of measurement of serum lipids and of utilizing lipid-lowering therapy, when appropriate, in older persons without contraindications to lipid-lowering drugs and with myocardial infarction (MI), stroke, peripheral arterial disease (PAD), and no coronary artery disease (CAD), stroke, or PAD. DESIGN: A retrospective analysis of charts of all older patients seen from January 1, 1997, through October 15, 1997, was performed to investigate the prevalence of measurement of serum lipids and utilization of lipid-lowering therapy, when appropriate, in older persons without contraindications to lipid-lowering drugs and with MI, stroke, PAD, and no CAD, stroke, or PAD. Patients with life-limiting comorbidities were not included in the study. SETTING: An academic, hospital-based geriatrics practice staffed by fellows in a geriatrics training program and full-time faculty geriatricians. PARTICIPANTS: A total of 373 men and 1119 women, mean age 80 +/- 8 years (range 59 to 103 years), were included in the study. MEASUREMENTS AND MAIN RESULTS: Serum low-density lipoprotein (LDL) cholesterol was measured in 201 of 391 patients (51%) with MI, in 78 of 187 patients (42%) with stroke, in 58 of 115 patients (50%) with PAD, and in 396 of 926 patients (43%) with no CAD, stroke, or PAD. In patients with elevated serum LDL cholesterol levels, lipid-lowering drug therapy was given to eight of 15 patients (53%) <70 years of age with MI, to 34 of 63 patients (54%) 70 to 80 years of age with MI, and to 38 of 81 patients (47%) >80 years of age with MI (P not significant); to three of seven patients (43%) <70 years of age with stroke, to 12 of 26 patients (46%) 70 to 80 years of age with stroke, and to 13 of 32 patients (41%) >80 years of age with stroke (P not significant); to two of four patients (50%) <70 years of age with PAD, to seven of 17 patients (41%) 70 to 80 years of age with PAD, and to 10 of 25 patients (40%) >80 years of age with PAD (P not significant); and to six of 15 patients (40%) <70 years of age with no CAD, stroke, or PAD, to 26 of 70 patients (37%) 70 to 80 years of age with no CAD, stroke or PAD, and to 14 of 47 patients (30%) >80 years of age with no CAD, stroke, or PAD (P not significant). None of the other patients with MI, stroke, PAD, or no CAD, stroke, or PAD was treated with diet or lipid-lowering drugs. CONCLUSIONS: Measurement of serum LDL cholesterol and of appropriate use of lipid-lowering drugs and diet in older patients with MI, stroke, PAD, and no CAD, stroke, or PAD is underutilized in an academic, hospital-based geriatrics practice. |
| Unesterified cholesterol content of human sperm regulates the response of the acrosome to the agonist, progesterone Zarintash, R. J. and N. L. Cross (1996), Biol Reprod 55(1): 19-24. Abstract: Human sperm become responsive to inducers of the acrosome reaction if they are washed free of seminal plasma and incubated in an appropriate medium. We tested the hypothesis that sperm must lose cholesterol during incubation in order to become responsive to the agonist, progesterone. Freshly ejaculated sperm contained 2.92 +/- 0.202 nmol unesterified cholesterol/10(7) sperm (mean +/- SEM, n = 18). When incubated for 24 h in vitro, sperm suspensions lost 29 +/- 6% of their free cholesterol (n = 23). Sperm lost cholesterol slightly faster than they became acrosomally responsive. Adding cholesterol to the medium prevented sperm from losing cholesterol and from becoming responsive. Varying the cholesterol content of the medium had similar effects on loss of sperm cholesterol (ED50 = 406 nM) and acrosomal responsiveness (ED50 = 388 nM). Incubating sperm with a 1:150 dilution of seminal plasma (containing 5.18 microM cholesterol) also prevented sperm from losing cholesterol and from becoming responsive. Incubating sperm 24 h in medium containing 0.5 mg/ml phosphatidylcholine increased the amount of cholesterol lost and the number of sperm that became responsive. Our results support a model in which sperm unesterified cholesterol (or a molecule in equilibrium with it) suppresses acrosomal responsiveness. Sperm must lose unesterified cholesterol to become responsive to progesterone. |
| Unesterified cholesterol in granular, lattice, and macular dystrophies Rodrigues, M. M., H. S. Kruth, et al. (1993), Am J Ophthalmol 115(1): 112-4. |
| Unesterified plant sterols and stanols lower LDL-cholesterol concentrations equivalently in hypercholesterolemic persons Vanstone, C. A., M. Raeini-Sarjaz, et al. (2002), Am J Clin Nutr 76(6): 1272-8. Abstract: BACKGROUND: Plant sterols, in various forms, have been shown to reduce total and LDL-cholesterol concentrations. Particularly controversial at present is the effect of the degree of hydrogenation of the plant sterols on cholesterol-lowering efficacy and the responsible mechanisms. OBJECTIVE: Our goal was to examine the effect of supplementation with unesterified plant sterols and stanols on plasma lipid and phytosterol concentrations and cholesterol absorption, synthesis, and turnover. DESIGN: Fifteen otherwise healthy hypercholesterolemic subjects consumed each of 4 dietary treatments in a randomized crossover design. Unesterified sterols and stanols were blended into the butter component of the diet at a dosage of 1.8 g/d. The diets contained plant sterols (NS), plant stanols (SS), a 50:50 mixture of sterols and stanols (NSS), or cornstarch (control). RESULTS: Plasma total cholesterol concentrations were 7.8%, 11.9%, and 13.1% lower (P < 0.01) in the NS, SS, and NSS groups, respectively, than in the control group. LDL-cholesterol concentrations were 11.3%, 13.4%, and 16.0% lower (P < 0.03) in the NS, SS, and NSS groups, respectively, than in the control group. Plasma triacylglycerols and HDL-cholesterol concentrations did not differ significantly across diets. Cholesterol absorption efficiency was 56.0%, 34.4%, and 48.9% lower (P < 0.001) in the NS, SS, and NSS groups, respectively, than in the control group. The fractional synthesis rate was higher by 45.5% (P < 0.003) in the NSS group than in the control group. Plasma campesterol and sitosterol concentrations were higher (P < 0.01) in the NS group and sitosterol concentrations were lower (P < 0.01) in the SS group than in the control group. CONCLUSION: These data indicate that, in their free unesterified form, sterols and stanols lower plasma LDL cholesterol equivalently in hypercholesterolemic persons by suppressing cholesterol absorption. |
| Unexpected cholesterol measurement in patients with hypercholesterolemia Diaz Calleja, C., J. Pastor Pastor, et al. (1997), Med Clin (Barc) 109(7): 276-7. |
| Unexpected failure of bile acid malabsorption to stimulate cholesterol synthesis in sitosterolemia with xanthomatosis. Comparison with lovastatin Nguyen, L., G. Salen, et al. (1990), Arteriosclerosis 10(2): 289-97. Abstract: We examined the relationship between cholesterol synthesis and high affinity low density lipoprotein (LDL) catabolism in freshly isolated mononuclear leukocytes and plasma sterols and apolipoprotein concentrations in three homozygous and one heterozygous subject with sitosterolemia with xanthomatosis and in 12 control subjects. Observations in untreated subjects were compared during therapy with lovastatin or interruption of the enterohepatic circulation of bile acids. Plasma cholesterol, plant sterol, and apolipoprotein B concentrations declined more than 50% in the two homozygous sitosterolemic subjects after ileal bypass surgery. In contrast, plasma cholesterol, plant sterol, and apolipoprotein B concentrations remained constant in a homozygous sitosterolemic subject and declined only 7% in a heterozygous sitosterolemic subject during 20 weeks of lovastatin (40 mg/day) treatment compared to a 28% decrease in similarly treated control subjects. Lovastatin treatment decreased cholesterol synthesis more than 60% but did not increase high affinity catabolism of LDL further in the sitosterolemic cells, compared to a more than 20% rise in control mononuclear leukocytes. Conversely, bile acid malabsorption increased cholesterol synthesis 59%, total hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity 13%, and receptor-mediated LDL degradation 41% in control cells, but did not stimulate cholesterol synthesis or microsomal HMG-CoA reductase activity in sitosterolemic mononuclear leukocytes although receptor-mediated LDL catabolism rose an additional 26%. These results demonstrate a greater than expected decrease in plasma sterols and apolipoprotein B concentrations in sitosterolemic subjects after stimulation of bile acid synthesis because of the inability to up-regulate cholesterol production. We suggest that bile acid-sequestering drugs or ileal exclusion surgery may be more effective treatments to mobilize accumulated sterol deposits and prevent atherosclerosis in this disease. |
| Unexpected inhibition of cholesterol 7 alpha-hydroxylase by cholesterol in New Zealand white and Watanabe heritable hyperlipidemic rabbits Xu, G., G. Salen, et al. (1995), J Clin Invest 95(4): 1497-504. Abstract: We investigated the effect of cholesterol feeding on plasma cholesterol concentrations, hepatic activities and mRNA levels of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase and hepatic LDL receptor function and mRNA levels in 23 New Zealand White (NZW) and 17 Watanabe heritable hyperlipidemic (WHHL) rabbits. Plasma cholesterol concentrations were 9.9 times greater in WHHL than NZW rabbits and rose significantly in both groups when cholesterol was fed. Baseline liver cholesterol levels were 50% higher but rose only 26% in WHHL as compared with 3.6-fold increase with the cholesterol diet in NZW rabbits. In both rabbit groups, hepatic total HMG-CoA reductase activity was similar and declined > 60% without changing enzyme mRNA levels after cholesterol was fed. In NZW rabbits, cholesterol feeding inhibited LDL receptor function but not mRNA levels. As expected, receptor-mediated LDL binding was reduced in WHHL rabbits. Hepatic cholesterol 7 alpha-hydroxylase activity and mRNA levels were 2.8 and 10.4 times greater in NZW than WHHL rabbits. Unexpectedly, cholesterol 7 alpha-hydroxylase activity was reduced 53% and mRNA levels were reduced 79% in NZW rabbits with 2% cholesterol feeding. These results demonstrate that WHHL as compared with NZW rabbits have markedly elevated plasma and higher liver cholesterol concentrations, less hepatic LDL receptor function, and very low hepatic cholesterol 7 alpha-hydroxylase activity and mRNA levels. Feeding cholesterol to NZW rabbits increased plasma and hepatic concentrations greatly, inhibited LDL receptor-mediated binding, and unexpectedly suppressed cholesterol 7 alpha-hydroxylase activity and mRNA to minimum levels similar to WHHL rabbits. Dietary cholesterol accumulates in the plasma of NZW rabbits, and WHHL rabbits are hypercholesterolemic because reduced LDL receptor function is combined with decreased catabolism of cholesterol to bile acids. |
| Unfavourable impact of growth hormone (GH) discontinuation on body composition and cholesterol profiles after the completion of height growth in GH-deficient young adults Kohno, H., N. Ueyama, et al. (1999), Diabetes Obes Metab 1(5): 293-6. Abstract: AIM: Growth hormone (GH) plays an important role in the regulation of body composition and metabolism. GH deficiency is associated with obesity and hypercholesterolemia, which respond to GH treatment. In this study we evaluated changes in body composition and cholesterol profiles after discontinuation of GH therapy to assess atherogenic risk factors in GH-deficient patients. METHODS: We studied 18 male patients with GH deficiency 17-20 years of age at the time of discontinuing GH therapy. Body composition and cholesterol were measured 6 months before discontinuation of GH therapy with a weekly dose of 0.5 IU/kg (approximately 0.19 mg/kg), and immediately, 2 months, and 6 months after the end of GH therapy. RESULTS: Two months after termination of GH therapy the percentage of body fat and fat mass increased from 7.4% to 9.4% and from 3.8 kg to 5.0 kg, respectively, and remained high thereafter. Lean body mass decreased gradually, but the change was not significant. Lean body mass: fat mass ratio decreased from 14.7 at termination of GH therapy to 10.9 at the end of study. Total cholesterol (TC) showed a significant linear increase from 156 mg/dl immediately after discontinuation to 169 mg/dl 6 months after discontinuation of GH, whereas high-density lipoprotein cholesterol (HDLC) showed no change during the study. The TC to HDLC ratio showed a slight but insignificant trend toward an increase. There were no significant changes in any variables during the last 6 months of GH therapy. CONCLUSION: GH therapy in patients with GH deficiency can reduce risk factors for obesity-related diseases and atherosclerosis. These beneficial effects are reversed after discontinuation of GH therapy. Further long-term studies of the effects of the GH withdrawal on lipid profiles, adiposity and life expectancy must be performed. |
| Unfiltered coffee raises cholesterol Huijing, F. (2002), South Med J 95(6): 660-1. |
| Unfolding story of inclusion-body myositis and myopathies: role of misfolded proteins, amyloid-beta, cholesterol, and aging Askanas, V. and W. K. Engel (2003), J Child Neurol 18(3): 185-90. Abstract: Sporadic inclusion-body myositis and hereditary inclusion-body myopathies are progressive muscle diseases leading to severe disability. We briefly summarize their clinical pictures and pathologic diagnostic criteria and discuss the latest advances in illuminating their pathogenic mechanism(s). We emphasize how different etiologies might lead to the strikingly similar pathology and possibly similar pathogenic cascade. On the basis of our research, several processes seem to be important in relation to the still speculative pathogenesis, including (a) increased transcription and accumulation of amyloid-beta precursor protein and accumulation of its proteolytic fragment amyloid-beta; (b) abnormal accumulation of components related to lipid metabolism, for example, cholesterol, accumulation of which is possibly owing to its abnormal trafficking; (c) oxidative stress; (d) accumulations of other Alzheimer's disease-related proteins; and (e) a milieu of muscle cellular aging in which these changes occur. We discuss a potentially very important role of unfolded and/or misfolded proteins as a possible mechanism in the formations of the inclusion bodies and other abnormalities. |
| Unfolding the toxicity of cholesterol Zhang, K. and R. J. Kaufman (2003), Nat Cell Biol 5(9): 769-70. |
| Unilateral proptosis due to cholesterol granuloma Friling, R., T. Monos, et al. (1993), Harefuah 124(12): 761-2, 795. Abstract: Cholesterol granuloma is a rare cause of unilateral proptosis. We describe a 42-year-old man who presented with painless swelling of the left upper brow of a few months duration. Biopsy showed crystals of cholesterol surrounded by giant cells. |
| Unique epitope of apolipoprotein A-I expressed in pre-beta-1 high-density lipoprotein and its role in the catalyzed efflux of cellular cholesterol Fielding, P. E., M. Kawano, et al. (1994), Biochemistry 33(22): 6981-5. Abstract: The ability of mouse anti-apolipoprotein A-I (apo A-I) monoclonal antibodies to recognize pre-beta-HDL species in native plasma was determined. An antibody identifying residues 137-144 of the mature protein uniquely recognized pre-beta-1 HDL, an HDL species of low molecular weight implicated in early cholesterol transport from cell membranes to plasma Castro, G. R., & Fielding, C. J. (1988) Biochemistry 27, 25-29. Incubation of plasma with this antibody significantly inhibited the efflux of labeled cholesterol from cultured fibroblast monolayers. A second antibody, binding to residues 93-99 of apo A-I, recognized a second pre-beta-HDL species (pre-beta-2 HDL) but not pre-beta-1 HDL and did not inhibit cholesterol efflux. Several other antibodies had broad specificity for HDL (including pre-beta-1 HDL). This research suggests that apo A-I residues 137-144 are adjacent to or part of a structural site in pre-beta-1 HDL active in promoting the efflux of cellular cholesterol and that this site is not exposed in other HDL species. |
| Unique pathway for cholesterol uptake in fat cells Fazio, S. and M. F. Linton (2004), Arterioscler Thromb Vasc Biol 24(9): 1538-9. |
| Unique property of liver mitochondrial P450 to catalyze the two physiologically important reactions involved in both cholesterol catabolism and vitamin D activation Usui, E., M. Noshiro, et al. (1990), FEBS Lett 274(1-2): 175-7. Abstract: The cDNA for vitamin D 25-hydroxylase in rat liver mitochondria was transfected in COS cells in order to confirm our previous postulation that both 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol 27-hydroxylation and vitamin D 25-hydroxylation are catalyzed by a common enzyme. As a result it was found that both enzyme activities could be reconstituted from the solubilized extract of mitochondria of these cells, NADPH, NADPH-adrenodoxin reductase and adrenodoxin, giving unequivocal evidence that the two enzyme activities are catalyzed by a common enzyme. |