| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Impact of cholesterol reduction on peripheral arterial disease in the Program on the Surgical Control of the Hyperlipidemias (POSCH) Buchwald, H., H. R. Bourdages, et al. (1996), Surgery 120(4): 672-9. Abstract: BACKGROUND: Few lipid/atherosclerosis intervention trials have assessed the impact of cholesterol reduction on peripheral arterial disease. The 838 patients evaluated in the Program on the Surgical Control of the Hyperlipidemias (POSCH) trial represent more than the total number of patients in the seven previously reported studies. METHODS: Peripheral arterial disease in POSCH was assessed by progression of clinical disease, serial changes in the systolic blood pressure ankle/brachial index (ABI), and changes on sequential peripheral arteriograms. RESULTS: At the time of formal closure of the POSCH trial on July 19, 1990, claudication or limb-threatening ischemia was exhibited in 72 of 417 control group (CG) patients and in 54 of 421 intervention group (IG) patients (IG relative risk RR 0.702, 95% confidence interval CI 0.169 to 1.000, p = 0.049). With additional follow-up evaluation to September 30, 1994, clinical peripheral arterial disease was evident in 91 CG patients and 64 IG patients (RR 0.656, 95% CI 0.200 to 0.903, p = 0.009). At the 5-year follow-up evaluation, an ABI of less than 0.95 was present in 41 of 120 CG patients and in 24 of 126 IG patients, all of whom had an ABI of 0.95 or greater at baseline (RR in the IG of 0.557, 95% CI 0.360 to 0.863, p < 0.01). No appreciable differences were noted in the progression or regression of arteriographic peripheral arterial disease between the two groups. CONCLUSIONS: Effective cholesterol reduction in POSCH led to statistically significant differences between the control and the intervention groups in the development of clinically evident peripheral arterial disease and in the ABI values, but not in the peripheral arteriograms. Additional studies need to assess the correlation between peripheral arterial changes and coronary arterial changes and clinical atherosclerosis events. Intervention trials that study peripheral arterial disease have intrinsic value in the evaluation of the impact of risk factor modification on progression of atherosclerotic peripheral arterial disease. |
| Impact of hydrogenated fat consumption on endogenous cholesterol synthesis and susceptibility of low-density lipoprotein to oxidation in moderately hypercholesterolemic individuals Cuchel, M., U. S. Schwab, et al. (1996), Metabolism 45(2): 241-7. Abstract: The effects of replacing corn oil with corn oil margarine in stick form on endogenous cholesterol synthesis and susceptibility of low-density lipoprotein (LDL) to oxidation were assessed in 14 middle-aged and elderly men and women aged 63 +/- 12 years (mean +/- SD) with moderate hypercholesterolemia (mean LDL-cholesterol LDL-C, 4.24 +/- 0.59 mmol/L at the time of recruitment). Subjects consumed each of two diets for 32-day periods, one enriched in corn oil, which contained 30% of energy as fat (7% saturated fatty acid SFA, 9% monounsaturated fatty acid MUFA 0.4% 18:1n9 trans, and 11% polyunsaturated fatty acid PUFA) and 85 mg cholesterol/4.2 MJ, and one enriched in stick corn oil margarine, which contained 30% fat (8% SFA, 12% MUFA 4.2% 18:1n9trans, and 8% PUFA) and 77 mg cholesterol/4.2 MJ. Both diets were isocaloric and supplied by a metabolic research kitchen. Mean total cholesterol levels were lowest (P =.039) when subjects consumed the corn oil-enriched diet (5.01 +/- 0.51 mmol/L) as compared with the margarine-enriched diet (5.30 +/- 0.58 mmol/L). LDL-C levels were 3.24 +/- 0.51 and 3.50 +/- 0.54 mmol/L when subjects consumed corn oil-and margarine-enriched diets, respectively (P =.058). There were no significant differences in high-density lipoprotein cholesterol (HDL-C) or triglyceride concentrations between the two experimental periods. Consumption of the margarine-enriched diet versus the corn oil-enriched diet tended to result in lower cholesterol fractional synthetic rates (C-FSRs 0.0466 +/- 0.0175 and 0.0668 +/- 0.0298, respectively, P =.080) and cholesterol absolute synthetic rates (C-ASRs 1.1761 +/- 0.5375 and 1.6954 +/- 0.8685, respectively, P =.092); however, differences did not reach statistical significance. Consumption of the margarine-enriched diet versus the corn oil-enriched diet resulted in a significantly higher concentration of alpha-tocopherol in both plasma and LDL(P =.004 and P =.011, respectively). LDL particle size tended to be smaller after subjects consumed the margarine-enriched diet versus the corn oil-enriched diet (P =.103). Susceptibility of LDL to oxidation was similar after consumption of the corn oil- and margarine-enriched diets. These data suggest that an increased rate of endogenous cholesterol synthesis did not contribute to the higher plasma cholesterol concentrations during the period when subjects consumed the margarine-enriched diet. Therefore, the increase in cholesterol concentration resulting from margarine consumption was likely attributable, at least in part, to a decreased catabolic rate of cholesterol. Additionally, susceptibility of LDL to in vitro oxidation was not altered by consumption of hydrogenated fat. |
| Impact of Mediterranean diet education versus posted leaflet on dietary habits and serum cholesterol in a high risk population for cardiovascular disease Bemelmans, W. J., J. Broer, et al. (2000), Public Health Nutr 3(3): 273-83. Abstract: OBJECTIVE: To investigate the impact of intensive group education on the Mediterranean diet on dietary intake and serum total cholesterol after 16 and 52 weeks, compared to a posted leaflet with the Dutch nutritional guidelines, in the context of primary prevention of cardiovascular disease (CVD). DESIGN: Controlled comparison study of an intervention group given intensive group education about the Mediterranean diet and a control group of hypercholesterolaemic persons given usual care by general practitioners (GPs). SETTING: A socioeconomically deprived area in the Netherlands with an elevated coronary heart disease (CHD) mortality ratio. SUBJECTS: Two hundred and sixty-six hypercholesterolaemic persons with at least two other CVD risk factors. RESULTS: After 52 weeks, the intervention group decreased total and saturated fat intake more than the control group (net differences were 1.8 en% (95%CI 0.2-3.4) and 1.1 en% (95%CI 0. 4-1.9), respectively). According to the Mediterranean diet guidelines the intake of fish, fruit, poultry and bread increased in the intervention group, more than in the control group. Within the intervention group, intake of fish (+100%), poultry (+28%) and bread (+6%) was significantly increased after 1 year (P < 0.05). The intensive programme on dietary education did not significantly lower serum cholesterol level more (-3%) than the posted leaflet (-2%) (net difference 0.06 mmol l-1, 95%CI -0.10 to 0.22). Initially, the body mass index (BMI) decreased more in the intervention group, but after 1 year the intervention and control group gained weight equally (+1%). CONCLUSIONS: Despite beneficial changes in dietary habits in the intervention group compared with the control group, after 1 year BMI increased and total fat and saturated fat intake were still too high. |
| Impact of monocyte colony-stimulating factor upon beta-very low density lipoprotein (beta-VLDL) cholesterol metabolism in tetradecanoyl phorbol acetate-derived THP-1 cells Ishii, I., M. Yanagimachi, et al. (1994), Biochim Biophys Acta 1212(3): 278-84. Abstract: The effect of monocyte colony stimulating factor (M-CSF) on the beta-very low density lipoprotein (beta-VLDL) metabolism in THP-1 cells (human leukemia cell line) was studied. THP-1 cells treated with M-CSF decreased Latex Bead phagocytosis, but the cells incubated with 12-tetradecanoyl-phorbol-13-acetate (TPA) enhanced phagocytosis 2.5-fold. Binding activity of 125I-M-CSF to THP-1 cells was higher than that in THP-1 cells elicited with TPA. THP-1 cells incubated with M-CSF before TPA treatment were designated MT macrophages, and those incubated with M-CSF after TPA treatment were called TM macrophages. When these cells were incubated with beta-VLDL, the cholesterol ester content in MT macrophages was less than in TM macrophages. The uptake of 3Hcholesterol oleate-beta-VLDL in MT macrophages was the same as in TM macrophages. The released radioactivity from 3Hcholesterol oleate-beta-VLDL loaded MT macrophages was higher than that from TM macrophages. Acid cholesterol esterase activity and ACAT activity were the same in both types of macrophages. Neutral cholesterol esterase activity was higher in MT than in TM macrophages. These results suggested that beta-VLDL-induced cholesterol ester deposition in THP-1 cells-derived macrophages was suppressed by M-CSF, when M-CSF acted at the stage of monocytes (THP-1 cells), and that the reduction of cholesterol ester might be due to enhanced release of cholesterol from the cells with high neutral cholesterol esterase activity. |
| Impact of multiple risk factors on coronary artery disease: beyond total cholesterol. Introduction Gotto, A. M., Jr. (1998), Am J Cardiol 82(9A): 1Q-2Q. |
| Impact of nonprescriptive factors on low-density lipoprotein cholesterol reduction with statins Frolkis, J. P., G. L. Pearce, et al. (2004), Am J Cardiol 94(10): 1310-2. Abstract: Nonprescriptive factors, including patient adherence, can affect the fluctuations in low-density lipoprotein (LDL) cholesterol observed in the clinical setting. In 241 statin-treated patients, although drugs and doses remained fixed, 57% of patients initially successful in reaching LDL cholesterol targets showed subsequent increases in LDL cholesterol. Conversely, 60% of patients who initially failed to reach targets had subsequent reductions in LDL cholesterol, with nearly 1/3 eventually attaining their LDL cholesterol goals. |
| Impact of nutritional counseling in reducing serum cholesterol in public health service patients Batista Mda, C. and C. Franceschini Sdo (2003), Arq Bras Cardiol 80(2): 167-70, 162-6. Abstract: OBJECTIVE: To assess the impact of nutritional attention on the lipid profile and nutritional status of hypercholesterolemic patients attended in health centers of Belo Horizonte. METHODS: Using nutritional attendance patient record cards from two health units, the evolution of the lipid profile and the nutritional state (BMI) was monitored of 96 hypercholesterolemic patients who received diet. The patients were appraised at the following moments: initial (1st consultation), after 3 months (2nd consultation) and last consultation (variable for each patient). RESULTS: On the first attendance, 44,4% of the patients presented not only high total cholesterol and LDL-c, but also hypertriglyceridemia and 70.3% were overweight or obese, but most patients (75.6%) presented adequate HDL-c levels. There was significant reduction in the BMI, total cholesterol, LDL-c values (p < 0.01) and also in the triglyceride levels (p < 0.05) in the first three months, without alteration in the HDL-c levels. A significant reduction (p < 0.01) was observed in the frequency of individuals with high cholesterol (from 89.6% down to 47.9%), high and very high LDL-c (from 82.6% down to 45.7%), as well as high and very high triglyceride (from 43.6% down to 16.7%). The observed reduction in frequency of the low HDL-c was statistically meaningless. CONCLUSION: This study evidences the effect of the nutritional attention on lipid profile in hypercholesterolemic patients, reinforcing the need for a multiprofessional team to attend them at the public health services. |
| Impact of physicians' beliefs and practices on cholesterol levels in patients with type 2 diabetes: a longitudinal assessment Franciosi, M., F. Pellegrini, et al. (2005), Am Heart J 149(1): 104-11. Abstract: BACKGROUND: Clinical trials demonstrate significant benefit from cholesterol management for patients with type 2 diabetes. The aim of this work was to explore the correlates of lipid management in patients with type 2 diabetes, including the subjective beliefs of physicians, setting of care, and patient-related factors. METHODS: This longitudinal outcomes research study involved 2359 patients with type 2 diabetes recruited by 111 general practitioners and 214 physicians practicing in diabetes clinics. Physicians' beliefs were assessed through a questionnaire administered when the study started in 1998. Main outcome measures were total cholesterol (TC) and LDL cholesterol (LDL-C) levels over 3 years and the proportion of patients treated with lipid-lowering drugs (LLDs). RESULTS: Less than one-third of the physicians (27%) stated that they routinely started pharmacologic therapy for TC values > or =200 mg/dL (more aggressive), whereas 46% considered a TC level > or =240 mg/dL as the threshold for the initiation of treatment (less aggressive). During 3 years of observation, mean TC and LDL-C levels decreased from 215 +/- 40 mg/dL to 203 +/- 37 mg/dL and from 135 +/- 36 mg/dL to 126 +/- 35 mg/dL respectively, while the proportion of patients treated with LLDs increased from 13.2% to 24.6%; in particular, among individuals cared for by the more aggressive physicians, 30.0% were taking LLDs after 3 years, while only 17.7% of those followed by the less aggressive physicians and 18.1% of those followed by >1 physician were being treated with LLDs. Multilevel analysis showed that physicians' beliefs were an independent predictor of TC levels over the 3-year period. In patients treated with LLDs, TC levels decreased on average by 14%, and LDL-C levels decreased by 20%. CONCLUSION: Our data show that physicians' beliefs in more aggressive management strategies will result in better mean TC values over a 3-year period. |
| Impact of receiving blood cholesterol test results on dietary change Strychar, I. M., F. Champagne, et al. (1998), Am J Prev Med 14(2): 103-10. Abstract: INTRODUCTION: The study objective was to determine the impact of receiving results of a blood cholesterol test on changes in dietary behaviors among individuals participating in a Health Risk Appraisal Program. METHODS: This randomized trial of maintenance employees at six hospitals included two groups: Group 1 received their blood cholesterol test results at the pretest; Group 2 received results only at the posttest (16-20 weeks later). The pretest interview included (1) a 24-hour dietary recall; (2) an evaluation of dietary behaviors and suggestions on how to change; (3) height, weight, and blood cholesterol measurement. Five hundred employees participated, and 429 eligible employees completed both pretest and posttest interviews. RESULTS: Blood cholesterol levels decreased by 4.8% (P <.001) and saturated fat intake decreased by 7.4% (P <.05). Regression analyses indicated that individuals more likely to have lowered saturated fat intake had higher pretest saturated fat intakes, had a family history of high blood cholesterol, and were light-maintenance employees (P <.05); no other variables were associated (receiving blood cholesterol test results, previous blood cholesterol test, pretest blood cholesterol levels, personal history of heart disease, BMI, age, gender, tobacco/alcohol use). Among subjects with normal cholesterol levels, those not receiving blood test results reduced saturated fat intake more than those receiving test results; both groups had similar saturated fat intakes (> 12%) greater than recommended intake (< 10%). CONCLUSIONS: Screening programs should include an assessment of saturated fat intake as screening for blood cholesterol may provide normocholesterolemic subjects with a false sense of security. |
| Impact of simvastatin, niacin, and/or antioxidants on cholesterol metabolism in CAD patients with low HDL Matthan, N. R., A. Giovanni, et al. (2003), J Lipid Res 44(4): 800-6. Abstract: The HDL Atherosclerosis Treatment Study (HATS) demonstrated a clinical benefit in coronary artery disease patients with low HDL cholesterol (HDL-C) levels treated with simvastatin and niacin (S-N) or S-N plus antioxidants (S-N+A) compared with antioxidants alone or placebo. Angiographically documented stenosis regressed in the S-N group but progressed in all other groups. To assess the mechanism(s) responsible for these observations, surrogate markers of cholesterol absorption and synthesis were measured in a subset of 123 HATS participants at 24 months (on treatment) and at 38 months (off treatment). Treatment with S-N reduced desmosterol and lathosterol levels (cholesterol synthesis indicators) 46% and 36% (P < 0.05), respectively, and elevated campesterol and beta-sitosterol levels (cholesterol absorption indicators) 70% and 59% (P < 0.05), respectively, relative to placebo and antioxidant but not S-N+A. Treatment with antioxidants alone had no significant effect. Combining S-N with antioxidants reduced desmosterol and lathosterol by 37% and 31%, and elevated campesterol and beta-sitosterol levels by 54% and 46%, but differences did not attain significance. Mean change in percent stenosis was positively associated with a percent change in lathosterol (r = 0.26, P < 0.005) and negatively associated with a percent change in beta-sitosterol (r = -0.21, P < 0.01). These data suggest that changes in stenosis were attributable, in part, to changes in cholesterol metabolism. |
| Impact of subdermal norgestrel on hepatic acyl-coenzyme A:cholesterol- acyltransferase (ACAT) activity: possible antiatherogenic effect Letterie, G. S. (2000), Contraception 61(6): 391-4. Abstract: The impact of subdermally placed ethinyl estradiol, norgestrel, and the combination of the two on cholesterol metabolism as measured by hepatic acyl:cholesterol-acyltransferase (ACAT) activity was examined in the rat model. A total of 48 rats were assigned to one of 6 groups, receiving either 0.1 mg or 1.0 mg of ethinyl estradiol daily, 1.0 or 10 mg of norgestrel daily, and combinations of either 0.1 mg ethinyl estradiol/1.0 mg norgestrel or 1.0 mg ethinyl estradiol/10 mg norgestrel daily. All drugs were administered through subdermally placed time release capsules. The administration of norgestrel only in either 1.0 mg or 10 mg resulted in significantly lower rates of ACAT activity (0.77 +/- 0.566 and 0.91 +/- 0.239 pmol/mg/min, respectively). The combination of 1.0 ethinyl estradiol and 10 mg norgestrel resulted in a significant increase in ACAT activity to 2.17 +/- 0.873. This combination also resulted in significantly greater weight loss at the conclusion of treatment 247.83 +/- 6.2 g (pre) vs. 205.50 +/- 10.6 (post). There were no other differences in ACAT activity between groups and no other differences in weight, both between groups and pre- and post-treatment within groups. In summary, subdermally placed norgestrel resulted in a significant lowering of ACAT activity not seen with either administration of ethinyl estradiol alone or the combination of ethinyl estradiol and norgestrel in doses ranging from 0.1 to 1.0 mg of ethinyl estradiol and 1.0 to 10.0 mg of norgestrel. Significantly increased ACAT activity for the combination of 1.0 ethinyl estradiol and 10 mg norgestrel over either ethinyl estradiol or norgestrel alone or a lower dose combination suggests a dose-related threshold and drug-drug interaction for this effect. These results suggest that subdermally placed norgestrel may result in significantly lower ACAT activity and may have a potential role as an antiatherogenic treatment. |
| Impact of the cholesterol education program for nurses: a pilot program evaluation Allen, J. (1993), Cardiovasc Nurs 29(1): 1-5. |
| Impact of the new National Cholesterol Education Program (NCEP) guidelines on patient management Harmel, A. P. and K. Berra (2003), J Am Acad Nurse Pract 15(8): 350-60. Abstract: PURPOSE: To update nurse practitioners (NPs) on the latest National Cholesterol Education Program (NCEP) guidelines for the management of high blood cholesterol in adults. DATA SOURCES: The 2001 NCEP Adult Treatment Panel (ATP) III guidelines and supporting scientific reviews and reports of clinical trials related to the evidence upon which the guidelines are based. CONCLUSIONS: The many new features of the ATP III guidelines include an increased emphasis on the patient with multiple risk factors in order to identify appropriate candidates for primary prevention and on more stringent classifications of elevated lipid/lipoprotein levels. However, elevated levels of low-density lipoprotein (LDL) cholesterol continue to be the focus for both primary and secondary prevention, and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are clearly the drugs of choice for decreasing LDL cholesterol in most patients. IMPLICATIONS FOR PRACTICE: Because NPs play key roles in optimizing treatment management, it is important that they become familiar with, and be prepared to help implement, these latest guidelines. By embracing the global risk assessment approach of ATP III and aggressively treating all at-risk patients, NPs can take a proactive role in helping to halt the progression of coronary heart disease and its consequences. |
| Impact of the third cholesterol report from the adult treatment panel of the national cholesterol education program on the clinical laboratory Warnick, G. R., G. L. Myers, et al. (2002), Clin Chem 48(1): 11-7. Abstract: BACKGROUND: The US National Cholesterol Education Program has recently released the third report of the Adult Treatment Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Incorporating new evidence and more consistent with other international intervention programs, these more complex guidelines will considerably expand indications for treatment. The implications for clinical laboratories are summarized in this report. CONTENT: LDL-cholesterol (LDL-C) remains the major focus for classification and treatment, whereas diabetes, the presence of multiple risk factors, including the metabolic syndrome, and increased triglycerides (TGs), will now require more intensive management. For screening, a fasting lipoprotein profile is recommended, adding LDL-C and TGs to the previous measurements of total cholesterol and HDL-cholesterol (HDL-C). Lowering the cutpoints defining optimal LDL-C 100 mg/dL (2.58 mmol/L) and normal TGs 150 mg/dL (1.70 mmol/L) and raising the cutpoint for low HDL-C to 40 mg/dL (1.03 mmol/L) will select more patients for treatment. A new marker, non-HDL-C, becomes a secondary target in treating high TGs. CONCLUSIONS: Laboratories will need to adjust reporting formats and interpretations and can expect more requests for tests to characterize secondary causes of dyslipidemia, e.g., diabetes, and for the so-called "emerging risk factors", e.g., lipoprotein(a), homocysteine, and C-reactive protein. |
| Impact of time-interval after transplantation and therapy with fibrates on serum cholesterol levels in renal transplant patients Fuhrer, J. A., A. Montandon, et al. (1993), Clin Nephrol 39(5): 265-71. Abstract: It is unclear to what extent different immunosuppressive regimens contribute to increased serum cholesterol levels observed in renal transplant patients after prolonged periods of immunosuppression (i.e. 3 and 5 years following kidney grafting). Therefore 2 groups of renal transplant patients were evaluated with respect to serum cholesterol 3 years (n = 103) and 5 years (n = 66) after transplantation: Group 1: prednisone (Pred)/azathioprine (Aza) 3 years (y): n = 52; 5 y: n = 49; mean prednisone dose 12 +/- 1 mg/day; group 2: cyclosporine A (CsA) alone or in combination with Pred (3 y: n = 51; 5 y: n = 17; prednisone dose 4 +/- 2 mg/day, p < 0.001 vs group 1). The groups were similar with respect to age, sex, body mass index, time interval after transplantation, underlying kidney diseases and concomitant drug therapy. Serum cholesterol levels were persistently higher in patients of group 2 when compared to group 1 (3 years: 7.3 +/- 0.2 vs 6.7 +/- 0.2 mmol/l, p < 0.01; 5 years: 7.5 +/- 0.1 vs 6.6 +/- 0.3 mmol/l, p < 0.01) despite 75% lower daily doses of Pred (p < 0.001) in CsA treated patients (group 2). Before transplantation, patients exhibited a similar distribution of serum cholesterol levels when compared to age, sex and body mass index matched healthy subjects. In contrast 3 and 5 years following transplantation 72% of the patients had serum cholesterol levels above 6.5 mmol/l, whereas in normal subjects, 60% had serum cholesterol levels below 6.5 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Impaired absorption of cholesterol and bile acids in patients with an ileoanal anastomosis Hakala, K., M. Vuoristo, et al. (1997), Gut 41(6): 771-7. Abstract: BACKGROUND: No data exist on cholesterol absorption in patients with an ileoanal anastomosis (IAA). AIMS: To study cholesterol absorption and its effects on cholesterol and bile acid metabolism in patients with an IAA. PATIENTS AND METHODS: Cholesterol absorption, and serum, biliary, and faecal lipids were studied in 24 patients with an IAA and 20 controls. RESULTS: Fractional cholesterol absorption was significantly lower in the patients (36% versus 47% in controls). Surprisingly, the calculated intestinal influx of endogenous cholesterol was reduced so that the absolute absorption of cholesterol was decreased; elimination of cholesterol as faecal neutral steroids remained normal. Thus, the slightly increased cholesterol synthesis was mainly due to increased faecal bile acid excretion, which, in turn, was associated with reduced absorption and biliary secretion of bile acids. Serum total and low density lipoprotein (LDL) cholesterol and LDL triglycerides were lower in the patients. Molar percentage and saturation index of biliary cholesterol were slightly higher in patients with an IAA. Proportions of secondary bile acids in bile and faeces were diminished, and faecal unidentified bile acids were higher in patients. CONCLUSIONS: Cholesterol absorption is significantly impaired in patients with an IAA, and is closely related to changes in serum and biliary lipids observed in these patients. |
| Impaired biliary cholesterol secretion and decreased gallstone formation in apolipoprotein E-deficient mice fed a high-cholesterol diet Amigo, L., V. Quinones, et al. (2000), Gastroenterology 118(4): 772-9. Abstract: BACKGROUND & AIMS: Because apolipoprotein E (apoE) is a key cholesterol transport molecule involved in the hepatic uptake of chylomicron cholesterol, it may play a critical role in controlling bile cholesterol elimination and cholesterol gallstone formation induced by dietary cholesterol. To test this hypothesis, we studied biliary lipid secretion and gallstone formation in apoE-deficient mice fed cholesterol-rich diets. METHODS: Bile lipid outputs and gallstone sequence events were analyzed in apoE-deficient mice fed a high-cholesterol diet or a lithogenic diet compared with control animals. RESULTS: A high-cholesterol diet increased biliary cholesterol secretion and gallbladder bile cholesterol concentration in wild-type mice; the increase in bile cholesterol secretion was significantly attenuated in apoE-deficient mice. ApoE knockout mice fed a high-cholesterol lithogenic diet had a markedly lower frequency of gallbladder bile cholesterol crystal and gallstone formation than wild-type mice, which was most likely a result of the decreased cholesterol saturation index found in gallbladder bile of apoE-deficient mice. CONCLUSIONS: These results show that apoE expression is an important factor for regulating both biliary secretion of diet-derived cholesterol as well as diet-induced cholesterol gallstone formation in mice. |
| Impaired biliary lipid secretion in obese Zucker rats: leptin promotes hepatic cholesterol clearance VanPatten, S., N. Ranginani, et al. (2001), Am J Physiol Gastrointest Liver Physiol 281(2): G393-404. Abstract: Human obesity is associated with elevated plasma leptin levels. Obesity is also an important risk factor for cholesterol gallstones, which form as a result of cholesterol hypersecretion into bile. Because leptin levels are correlated with gallstone prevalence, we explored the effects of acute leptin administration on biliary cholesterol secretion using lean (FA/-) and obese (fa/fa) Zucker rats. Zucker (fa/fa) rats become obese and hyperleptinemic due to homozygosity for a missense mutation in the leptin receptor, which diminishes but does not completely eliminate responsiveness to leptin. Rats were infused intravenously for 12 h with saline or pharmacological doses of recombinant murine leptin (5 microg x kg(-1) x min(-1)) sufficient to elevate plasma leptin concentrations to 500 ng/ml compared with basal levels of 3 and 70 ng/ml in lean and obese rats, respectively. Obesity was associated with a marked impairment in biliary cholesterol secretion. In biles of obese compared with lean rats, bile salt hydrophobicity was decreased whereas phosphatidylcholine hydrophobicity was increased. High-dose leptin partially normalized cholesterol secretion in obese rats without altering lipid compositions, implying that both chronic effects of obesity and relative resistance to leptin contributed to impaired biliary cholesterol elimination. In lean rats, acute leptin administration increased biliary cholesterol secretion rates. Without affecting hepatic cholesterol contents, leptin downregulated hepatic activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, upregulated activities of both sterol 27-hydroxylase and cholesterol 7alpha-hydroxylase, and lowered plasma very low-density lipoprotein cholesterol concentrations. Increased biliary cholesterol secretion in the setting of decreased cholesterol biosynthesis and increased catabolism to bile salts suggests that leptin promotes elimination of plasma cholesterol. |
| Impaired cellular cholesterol efflux by oxysterol-enriched high density lipoproteins Gesquiere, L., N. Loreau, et al. (1997), Free Radic Biol Med 23(4): 541-7. Abstract: One of the proposed antiatherogenicity role of high-density lipoproteins (HDL) is believed to stimulate removal of cholesterol from the peripheral cells back to the liver for excretion. We have investigated the effects of oxidation-related modifications of HDL on their ability to stimulate cholesterol efflux from cultured cells. Human HDL (HDL3, 1.13 < d < 1.21 g/ml) have been modified either by malondialdehyde or by copper-mediated oxidation (Ox-HDL3). Compared with native HDL3, the modified HDL3 resulted in a significantly reduced efflux of labeled cholesterol from preloaded macrophages (P388D1 cell line). Analysis of lipid composition of Ox-HDL3 by gas chromatography revealed the presence of oxysterols (OS). Enrichment of native HDL3 with oxysterols resulted in a reduced capacity to stimulate cholesterol efflux. The reduced ability of OS-enriched HDL3 to elicit cholesterol efflux may contribute to cellular cholesterol accumulation and subsequently to atherosclerosis. |
| Impaired cholesterol esterification in Niemann-Pick disease model mouse Tokoro, T., T. Yamamamoto, et al. (1991), No To Hattatsu 23(1): 98-100. |