| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Importance of different pathways of cellular cholesterol efflux Yancey, P. G., A. E. Bortnick, et al. (2003), Arterioscler Thromb Vasc Biol 23(5): 712-9. Abstract: The removal of excess free cholesterol from cells by HDL or its apolipoproteins is important for maintaining cellular cholesterol homeostasis. This process is most likely compromised in the atherosclerotic lesion because the development of atherosclerosis is associated with low HDL cholesterol. Multiple mechanisms for efflux of cell cholesterol exist. Efflux of free cholesterol via aqueous diffusion occurs with all cell types but is inefficient. Efflux of cholesterol is accelerated when scavenger receptor class-B type I (SR-BI) is present in the cell plasma membrane. Both diffusion-mediated and SR-BI-mediated efflux occur to phospholipid-containing acceptors (ie, HDL and lipidated apolipoproteins); in both cases, the flux of cholesterol is bidirectional, with the direction of net flux depending on the cholesterol gradient. The ATP-binding cassette transporter AI (ABCA1) mediates efflux of both cellular cholesterol and phospholipid. In contrast to SR-BI-mediated flux, efflux via ABCA1 is unidirectional, occurring to lipid-poor apolipoproteins. The relative importance of the SR-BI and ABCA1 efflux pathways in preventing the development of atherosclerotic plaque is not known but will depend on the expression levels of the two proteins and on the type of cholesterol acceptors available. |
| Importance of exogenous cholesterol in diabetic rats: effects of treatment with insulin or with an acyl-CoA:cholesterol acyltransferase inhibitor Maechler, P., C. B. Wollheim, et al. (1993), Ann Nutr Metab 37(4): 199-209. Abstract: Contrary to normal rats, diabetic rats fed a cholesterol-rich diet become markedly hyperlipidemic. We have previously reported J Lipid Res 1992; 33:1475-14841bd that the intestinal acyl-CoA:cholesterol acyltransferase (ACAT) plays a major role in the initiation of diabetes-associated hypercholesterolemia. In the present study, we have shown that within the 3 days following diabetes induction by streptozotocin, diabetic rats responded to dietary cholesterol in a dose-dependent manner and their livers developed a large capacity to store cholesteryl esters (up to 10.6 +/- 1.4 mg/g tissue). We also examined the effects of treatments with insulin or with the ACAT inhibitor CL-277082 on the uptake of exogenous 3H-cholesterol in 3-day diabetic rats. The amount of 3H-cholesterol in chylomicrons was dramatically increased by the diabetic state (+110%; p < 0.01) reflecting a higher rate of cholesterol absorption compared to normal rats. This change was dependent on the ACAT activity since the CL-277082 treatment largely prevented the appearance of 3H-cholesterol in chylomicrons (-88%; p < 0.001), and as a consequence in the other lipoprotein classes. Insulin treatment reduced only by 35% (p < 0.05) the 3H-cholesterol in chylomicrons compared to the diabetic control rats, and failed to normalize the resulting lipoprotein profile. These results indicate that as early as 3 days after diabetes induction, diabetic rats are highly sensitive to dietary cholesterol concentrations, and that insulin deficiency is not the sole factor involved in the cholesterol hyperabsorption, which was totally suppressed by the ACAT inhibitor treatment. |
| Importance of HDL cholesterol determination in the evaluation of coronary risk in clinical practice Gil, V. F., F. Buhigues, et al. (1995), Aten Primaria 16(5): 254-60. Abstract: OBJECTIVE. To validate to what extent the isolated determination of total Cholesterol (TC) is effective when seeking to predict coronary risk. DESIGN. An observational crossover study of the analytic determinations of the clinics which systematically request TC and HDL-Cholesterol (HDL)--case-finding method. SETTING. Health Centre. PARTICIPANTS. 631 analytic determinations, with samples from people who attended a Health Centre between May and November 1992, were studied. MEASUREMENTS AND MAIN RESULTS. As proof of certainty the Atherogenic Index (AI) was used for the relative risks (RR) of suffering a coronary event in line with the Framingham study. The confidence limits (CL) were calculated to 95% in order to quantify random error and permit comparison. On varying the cut-off points of TC the indicators changed, being more sensitive (S) and less specific (E) with the lower figures: 180 mg/dl, RR > 1, S = 97.5% (CL: 100-94.7) and E = 30.5% (36.8-24.2); RR > 2, S = 100%, E = 22.1% (26.9-17.3) and RR > 3, S = 100%, E = 20.8% (25.3-16.3). As values of TC increase, S diminishes and E increases: 250 mg/dl, RR > 1, S = 48.3% (57.2-39.4), E = 87.2% (91.8-82.6); RR > 2, S = 58.6% (76.5-40.7), E = 77.2% (82-72.4) and RR > 3, S = 63.6% (92-35.2), E = 75.3% (80.1-70.5). CONCLUSIONS. HDL must be determined if TC is -200 mg/dl. If everyone with RR > 2 is to be detected, HDL-cholesterol from TC > or = 180 mg/dl must be measured. |
| Importance of HDL cholesterol levels and the total/ HDL cholesterol ratio as a risk factor for coronary heart disease in molecularly defined heterozygous familial hypercholesterolaemia Real, J. T., F. J. Chaves, et al. (2001), Eur Heart J 22(6): 465-71. Abstract: AIMS: To assess the relationship of the lipid profile to coronary heart disease in a group of heterozygous familial hypercholesterolaemic subjects with similar age, sex, body mass index, prevalence of angiotensin converting enzyme DD genotype and type of low density lipoprotein receptor mutation. METHODS AND RESULTS: A total of 66 molecularly defined heterozygous familial hypercholesterolaemic subjects, 33 of whom had coronary heart disease, were studied. Clinical features, cardiovascular risk factors and lipid parameters were compared in both groups. Familial hypercholesterolaemic patients with coronary heart disease showed significantly lower values of mean plasma HDL cholesterol and a higher total/HDL cholesterol ratio as compared with familial hypercholesterolaemic subjects free of coronary heart disease. Total and LDL cholesterol concentrations were higher in patients with coronary heart disease, without reaching statistical significance. No differences in plasma lipoprotein(a) levels on absolute and log-transformed values were observed between the two groups. In the whole familial hypercholesterolaemia group, plasma HDL cholesterol levels were related to plasma triglyceride values and to LDL receptor gene 'null mutations'. CONCLUSIONS: In familial hypercholesterolaemic subjects of similar age, gender, body mass index, systolic and diastolic blood pressure, and genetic factors that could influence coronary heart disease risk, plasma HDL cholesterol values and total/HDL cholesterol ratios are two important coronary risk factors. Hence, treatment of familial hypercholesterolaemia should focus not only on lowering total and LDL cholesterol levels, but also on increasing HDL cholesterol values for coronary heart disease prevention. More prospective and intervention trials should be conducted to establish the relationship of HDL cholesterol levels and coronary heart disease in familial hypercholesterolaemia. |
| Importance of high-density lipoprotein cholesterol and triglyceride levels in coronary heart disease Sprecher, D. L., T. R. Watkins, et al. (2003), Am J Cardiol 91(5): 575-80. |
| Importance of high-density lipoprotein-phosphatidylcholine in secretion of phospholipid and cholesterol in bile Portal, I., T. Clerc, et al. (1993), Am J Physiol 264(6 Pt 1): G1052-6. Abstract: The purpose of this work was to evaluate biliary phosphatidylcholine (PC) secretion after intravenous infusion of high density lipoprotein (HDL)-3Hphosphatidylcholine (HDL-3HPC) in rats and to study the effect of infusion of dehydrocholic and cholic acids, which, respectively, inhibit and stimulate biliary secretion of PC. The data obtained in this study showed that, in the basal state, HDL-PC accounted for 38% of biliary PC. Dehydrocholic acid infusion caused only a "residual" secretion of HDL-PC in the bile; however, cholic acid infusion stimulated the secretion of HDL-PC as well as PC from intrahepatic microsomes. The low level of radioactivity of HDL-PC in intrahepatic compartments suggests that HDL-PC taken up by the liver is predestined for the bile secretion. The correlation between the kinetics of bile secretion of HDL-cholesterol and HDL-3HPC suggests the importance of HDL-PC in reverse transport of cholesterol to the liver and its transport to the bile. The differences between the effects of dehydrocholic acid and cholic acid infusions can be explained by the differences in bile salts binding to the surface of HDL. |
| Importance of LDL/HDL cholesterol ratio as a predictor for coronary heart disease events in patients with heterozygous familial hypercholesterolaemia: a 15-year follow-up (1987-2002) Panagiotakos, D. B., C. Pitsavos, et al. (2003), Curr Med Res Opin 19(2): 89-94. Abstract: This study evaluated the prognostic significance of several risk factors on the outcome of coronary heart disease (CHD) in 639 cardiovascular disease-free subjects with heterozygous familial hypercholesterolaemia (FH). During the 15-year follow-up, 53 (18%) men and 34 (9.8%) women had a CHD event (men vs women, p < 0.001). The age-adjusted 15-year event rate was 3% (87 events/2915 person-years). Smoking increased the CHD risk (hazard ratio = 2.45, p < 0.001), women had a 74% lower risk of a vascular event, compared to men, after controlling for the postmenopausal status (hazard ratio = 0.26, p < 0.001). A one-unit difference in low density lipoprotein (LDL)/high density lipoprotein cholesterol (HDL) cholesterol ratio was associated with a 17% higher risk (hazard ratio = 1.17, p < 0.05); hypertension increased the risk for an adverse event (hazard ratio = 3.02, p < 0.05) and a 1 mg/dl increase in plasma fibrinogen level was associated with a 4% higher CHD risk (hazard ratio = 1.04, p < 0.05). With the power of the 15 years of prospective evaluation, the study shows that increased smoking, hypertension and LDL cholesterol levels eight times more than HDL cholesterol predicts an adverse CHD event, in patients with FH. |
| Importance of measuring plasma cholesterol precursors Bodamer, O. A. and W. J. Craigen (1999), Am J Med Genet 82(2): 199. |
| Importance of routine measurement of HDL with total cholesterol in diabetic patients Feher, M. D., J. Stevens, et al. (1992), J R Soc Med 85(1): 8-11. Abstract: The prevalence of hypercholesterolaemia and the frequency of a reduced HDL-cholesterol (at different cholesterol concentrations) were evaluated in a group of 400 diabetic patients attending a single diabetic clinic. Despite regularly supervised diabetes, including dietary advice, over one quarter of the patients had a serum total cholesterol concentration greater than 6.5 mmol/l, while over a quarter of the non-insulin treated and one eighth of the insulin treated diabetic subjects had an HDL-cholesterol less than 0.9 mmol/l, with a greater prevalence in the males compared with the females. More than 60% of all the diabetic patients who had a reduced HDL-cholesterol less than 0.9 mmol/l also had a total cholesterol concentration less than 6.5 mmol/l. When the total/HDL-cholesterol ratio was calculated more non-insulin treated subjects had a value greater than 4.5 as compared with insulin treated diabetic patients. When comparisons were made between an age matched group of diabetic patients (n = 185) and a group of non-diabetic subjects attending for a health screen (n = 155), the frequencies of serum cholesterol concentrations greater than 5.2, 6.5, and 7.8 mmol/l were similar for both groups. Significantly greater numbers of diabetic patients had a reduced HDL-cholesterol less than 0.9 mmol/l (at any level of serum cholesterol) and a total/HDL cholesterol ratio greater than 4.5. This study has shown that the measurement of serum total cholesterol concentration alone will not characterize many subjects who are at risk of macrovascular complications due to a reduced HDL-cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Importance of serum cholesterol level in development of diabetic autonomic neuropathy Ueda, H., N. Kuroda, et al. (1993), Diabetes Res Clin Pract 21(2-3): 123-6. Abstract: Changes of cardiac beat-to-beat variation (BBV)--an index of autonomic nerve function--were examined on 2 occasions in an interval of 3.7-5.9 years in 33 diabetics. A total of 204 healthy people, ranging from 11 to 88 years of age, were also subjected to the BBV measurement as controls. In diabetics, a lower rate of change of BBV than the control value was considered as deterioration. Glycohemoglobin was measured every month. The mean of serum cholesterol on the 2 occasions nearest to each time BBV examination was taken for the evaluation of cholesterol level. No significant difference was observed in the control state of blood glucose in terms of glycohemoglobin between the groups with and without BBV deterioration. In 20 subjects with normal cholesterol level, 11 showed a BBV deterioration, and in 13 subjects with abnormal cholesterol level 12 deteriorated in BBV. Therefore, diabetics with normal serum cholesterol level did not seem to exacerbate autonomic neuropathy in terms of BBV. |
| Importance of the confounding factors age and sex in the correlation of serum uric acid, cholesterol and triglyceride levels Gathof, B. S., M. A. Schreiber, et al. (1991), Adv Exp Med Biol 309A: 231-4. |
| Imprinting of high sensitivity to a high-cholesterol diet by nutrition in early life Poledne, R. and J. Hajna (1998), Physiol Res 47(2): 95-101. Abstract: Imprinting of an increased sensitivity to a high-fat, high cholesterol (HFHC) diet by dietary manipulation in early life was studied in two strains of rat, i.e. in Prague hereditary hypercholesterolaemic rats (PHHC) and Wistar rats, from which the PHHC strain was obtained by selection and inbreeding. Whereas no effect of early life nutrition on cholesterolaemia induced by HFHC diet was found in control Wistar rats, significant imprinting of increased sensitivity to the same diet was demonstrated in PHHC rats. This imprinting increased the concentration of apoB-containing lipoprotein and liver cholesterol concentration in animals fed HFHC diet for a period of two months after weaning. No effect of this imprinting on endogenous cholesterol synthesis could be demonstrated. It is concluded that imprinting of increased sensitivity to HFHC diet by dietary manipulation in early life is not a general phenomenon but depends on underlying genetic predisposition(s). |
| Improper dietary cholesterol restriction in the elderly Cefalu, C. A. (1995), Am Fam Physician 52(4): 1105. |
| Improved cholesterol management in coronary heart disease patients enrolled in an HMO Khoury, A. T., G. J. Wan, et al. (2001), J Healthc Qual 23(2): 29-33. Abstract: The purpose of the study was to describe the effect of physician reminders on the measurement of low-density lipoprotein cholesterol (LDL-C) levels and treatment to achieve an LDL-C goal of < or = 100 mg/dL in coronary heart disease (CHD) patients. After reminders were initiated, the number of CHD patients without a documented LDL-C was reduced from 30% to 18%, between January 1997 and July 1998, and the percentage of CHD patients achieving the LDL-C goal improved from 10% to 27%. Thus, reminders can be an effective tool in improving cholesterol management of CHD patients. In contrast, a cholesterol-lowering clinic made available to some physicians, in addition to the reminders, was rarely used. |
| Improved cholesterol-related knowledge and behavior and plasma cholesterol levels in adults during the 1980s Frank, E., M. A. Winkleby, et al. (1992), Jama 268(12): 1566-72. Abstract: OBJECTIVES--To determine whether cholesterol-related knowledge and behavior and plasma cholesterol levels were stable until the inception of large-scale national interventions in the middle to late 1980s, whether they subsequently improved, and whether these levels varied by subgroups. DESIGN, SETTING, AND PARTICIPANTS--Data were collected from 4173 adults aged 25 through 74 years in the two control cities (San Luis Obispo and Modesto, Calif) of the Stanford Five-City Project. Five separate, community-based surveys were conducted in 1979-1980, 1981-1982, 1983-1984, 1985-1986, and 1989-1990. RESULTS--Cholesterol-related knowledge and behavior and plasma cholesterol levels improved (P =.0001) in both cities after the early 1980s. Those who were more educated, female, older, or nonsmokers had significantly higher knowledge and behavior scores, and those who were younger, more educated, or normotensive had significantly lower plasma cholesterol levels. CONCLUSION--Improvements in this population's cholesterol-related knowledge and behavior and plasma cholesterol levels began in 1985-1986, suggesting that the extensive cholesterol interventions that began in the middle 1980s in the United States created positive cholesterol-related changes at the community level. |
| Improved plasma cholesterol levels in men after a nutrition education program at the worksite Baer, J. T. (1993), J Am Diet Assoc 93(6): 658-63. Abstract: Eighty management-level male employees participated in a company-sponsored comprehensive physical that included determination of plasma total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels and percentage of body fat. After the lipid screening, each employee met with a registered dietitian who explained the results of the lipid analysis and discussed risk factors for coronary heart disease with an emphasis on diet. Seventy employees had a triglyceride level above 5.17 mmol/L and were invited to participate in a nutrition education program. Thirty-three (mean age = 44 years) chose to participate (intervention group); the other 37 (mean age = 35 years) served as controls (control group). Thus, the design of the study was not random. All subjects completed 3-day dietary records before and after the nutrition education program. Nutrition intervention consisted of (a) individualized instruction about the step 1 diet; (b) group sessions (1 hour every 3 months) on eating out, dietary fiber, and maintaining heart healthy behaviors; and (c) individualized follow-up by telephone (one call per month). The results of the year-long program revealed that men in the intervention group decreased dietary intake of energy (2,546 +/- 162 kcal to 2,246 +/- 125 kcal) and cholesterol (444 +/- 5.3 mg to 304 +/- 1.6 mg) and percentage of energy from total fat (38 +/- 3.4% to 31 +/- 2.6%) and protein (24 +/- 3.5% to 20 +/- 2.2%). Their consumption of carbohydrate and dietary fiber increased (38 +/- 2.1% to 45 +/- 2.5% and 8.0 +/- 2.3 g to 23.0 +/- 3.5 g, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) |
| Improved retention of idarubicin after intravenous injection obtained for cholesterol-free liposomes Dos Santos, N., L. D. Mayer, et al. (2002), Biochim Biophys Acta 1561(2): 188-201. Abstract: To date there has been a focus on the application of sterically stabilized liposomes, composed of saturated diacylphospholipid, polyethylene glycol (PEG) conjugated lipids (5-10 mole%) and cholesterol (CH) (>30 mole%), for the systemic delivery of drugs. However, we are now exploring the utility of liposome formulations composed of diacylphospholipid conjugated PEG mixtures prepared in the absence of added cholesterol, with the primary objective of developing formulations that retain encapsulated drug better than comparable formulations prepared with cholesterol. In this report the stability of cholesterol-free distearoylphosphatidylcholine (DSPC):distearoylphosphatidylethanolamine (DSPE)-PEG(2000) (95:5 mol/mol) liposomes was characterized in comparison to cholesterol-containing formulations DSPC:CH (55:45 mol/mol) and DSPC:CH:DSPE-PEG(2000) (50:45:5 mol/mol/mol), in vivo. Circulation longevity of these formulations was determined in consideration of variables that included varying phospholipid acyl chain length, PEG content and molecular weight. The application of cholesterol-free liposomes as carriers for the hydrophobic anthracycline antibiotic, idarubicin (IDA), was assessed. IDA was encapsulated using a transmembrane pH gradient driven process. To determine stability in vivo, pharmacokinetic studies were performed using 'empty' and drug-loaded (3)Hcholesteryl hexadecyl ether radiolabeled liposomes administered intravenously to Balb/c mice. Inclusion of 5 mole% of DSPE-PEG(2000) or 45 mole% cholesterol to DSPC liposomes increased the mean plasma area under the curve (AUC(0-24h)) 19-fold and 10-fold, respectively. Cryo-transmission electron micrographs of IDA loaded liposomes indicated that the drug formed a precipitate within liposomes. The mean AUC(0-4h) for free IDA was 0.030 micromole h/ml as compared to 1.38 micromole h/ml determined for the DSPC:DSPE-PEG(2000) formulation, a 45-fold increase, demonstrating that IDA was retained better in cholesterol-free compared to cholesterol-containing liposomes. |
| Improved thin-layer chromatographic method for the separation of cholesterol, egg phosphatidylcholine, and their degradation products Gabriels, M., F. Camu, et al. (2002), J AOAC Int 85(6): 1273-87. Abstract: Degradation products of egg phosphatidylcholine (EPC) and cholesterol were analyzed with different normal- and reversed-phase thin-layer chromatography (TLC) systems. The best separation, in terms of the highest number of degradation products from both analytes, was obtained with a reversed-phase system, using butanol-methanol-water-96-98% (v/v) acetic acid (40 + 40 + 20 + 4, v/v/v/v) as the mobile phase after overnight saturation at 25 degrees C. A special development technique was used. After a first development, the plate was dried and a second development was performed in the same direction. This method enabled us to separate lysophosphatidylcholine, several free fatty acids and hydroperoxides, and several undefined degradation products of EPC and cholesterol. All products were visualized after the plate was dipped in a 1% (v/v) solution of 4-methoxybenzaldehyde in 98% sulfuric acid-96-98% (v/v) acetic acid-ethanol-water (2 + 10 + 60 + 30), presenting a blue color or a white spot against a colored background. After activation at 110 degrees C, a stable color for both analytes was reached after 12 min. Precision of <5% was obtained at 2 levels of analysis. Good linearity was obtained in the range of 5-30 microg for EPC (r = 0.991) and 5-40 microg for cholesterol (r = 0.991). These results show that TLC can be an inexpensive and easy alternative for the analysis of EPC and cholesterol. |
| Improvement in cholesterol metabolism in mice given chronic treatment of taurine and fed a high-fat diet Murakami, S., Y. Kondo-Ohta, et al. (1999), Life Sci 64(1): 83-91. Abstract: The effects of chronic treatment of taurine on hypercholesterolemia and atherosclerosis were examined in C57BL/6J mice fed a high-fat diet containing 15% fat and 1.25% cholesterol. Taurine was dissolved in drinking water at 1% (w/v) and was given to mice ad libitum during 6 months-feeding of a high-fat diet. Hypercholesterolemia occurred and lipid accumulation on the aortic valve was evident. Taurine treatment lowered serum LDL + VLDL cholesterol by 44% in mice fed a high-fat diet, while it elevated serum HDL cholesterol by 25%. As a result, the atherogenic index, the ratio of HDL to LDL + VLDL was markedly improved. Cholesterol content in the liver also decreased by 19% with taurine. Similar tendencies were seen in mice fed regular chow, but the changes were not significant. The area of aortic lipid accumulation, which served as an index of atherosclerosis, was reduced by 20% with taurine. In the liver, taurine doubled the activity of cholesterol 7alpha-hydroxylase. These observations, together with prior findings, suggest that the cholesterol-lowering action of taurine may relate to the increased conversion of cholesterol to bile acids via stimulation of cholesterol 7a-hydroxylase activity. Thus, chronic treatment of high-fat mice with taurine improves the abnormal profile of the serum lipoproteins, and thereby retards the progression of atherosclerosis. |
| Improvement in endothelial dysfunction with LDL cholesterol level < 80 mg/dl in type 2 diabetic patients Sheu, W. H., Y. T. Chen, et al. (2001), Diabetes Care 24(8): 1499-501. |