| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Influence of pravastatin, a specific inhibitor of HMG-CoA reductase, on hepatic metabolism of cholesterol Reihner, E., M. Rudling, et al. (1990), N Engl J Med 323(4): 224-8. Abstract: BACKGROUND. Inhibitors of the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, are now used frequently to treat hypercholesterolemia. We studied the effects of specific inhibition of cholesterol synthesis by one of these agents (pravastatin) on the hepatic metabolism of cholesterol in patients with gallstone disease who were scheduled to undergo cholecystectomy. METHODS. Ten patients were treated with pravastatin (20 mg twice a day) for three weeks before cholecystectomy; 20 patients not treated served as controls. A liver specimen was obtained from each patient at operation, and the activities of rate-determining enzymes in cholesterol metabolism as well as low-density-lipoprotein (LDL)-receptor binding activity were determined. RESULTS. Pravastatin therapy reduced plasma total cholesterol by 26 percent and LDL cholesterol by 39 percent (P less than 0.005). Serum levels of free lathosterol, a precursor of cholesterol whose concentration reflects the rate of cholesterol synthesis in vivo, decreased by 63 percent (P less than 0.005), indicating reduced de novo biosynthesis of cholesterol. Microsomal HMG-CoA reductase activity, when analyzed in vitro in the absence of the inhibitor, was increased 11.8-fold (1344 +/- 311 vs. 105 +/- 14 pmol per minute per milligram of protein in the controls; P less than 0.001). The expression of LDL receptors was increased by 180 percent (P less than 0.005), whereas the activities of cholesterol 7 alpha-hydroxylase (which governs bile acid synthesis) and of acyl-coenzyme A:cholesterol O-acyltransferase (which regulates cholesterol esterification) were unaffected by treatment. CONCLUSIONS. Inhibition of hepatic HMG-CoA reductase by pravastatin results in an increased expression of hepatic LDL receptors, which explains the lowered plasma levels of LDL cholesterol. |
| Influence of pregnancy, lactation and environment on some clinical chemical reference values in Danish landrace dairy goats (Capra hircus) of different parity--II. Plasma urea, creatinine, bilirubin, cholesterol, glucose and total serum proteins Mbassa, G. K. and J. S. Poulsen (1991), Comp Biochem Physiol B 100(2): 423-31. Abstract: 1. Plasma urea, creatinine, bilirubin, glucose, cholesterol and total serum proteins were determined in Danish landrace goats from five herds in early and late gestation, during lactation and in dry goats. The purpose was to determine if there are sustained alterations in the levels of these parameters due to pregnancy and lactation and whether the changes are dependent on age, parity and environment. 2. Urea, creatinine and bilirubin were higher in young non-pregnant goats than in others. Urea decreased in goats at early and mid-lactation directly proportional to parity so that the higher the parity the more the decrease. 3. Creatinine was higher in young and adult non-pregnant goats than in others. There was an increase in late lactation that was greater in goats of higher parity than in others. 4. Bilirubin was higher in the mid-lactation stage, much more in goats of higher parity than in others. 5. Glucose concentration was lower in pregnant than in lactating goats and increased during lactation. The decrease during pregnancy was greater in higher parity goats than in others. 6. Plasma cholesterol and total serum proteins increased during lactation directly proportional to parity. 7. There were significant differences in biochemical parameters between goats from different herds (within similar physiological states). 8. Sustained alterations of these biochemical parameters occur during pregnancy and lactation in goats; the magnitude of changes depends on age and parity, and varies between herds. |
| Influence of protein/lipid ratio of diet on cholesterol synthesis and esterification in eel liver Burgos, C., M. Castillo, et al. (1993), Arch Int Physiol Biochim Biophys 101(1): 53-5. Abstract: The effect of protein/lipid ratio of diets on hepatic cholesterol has been studied in European eel and correlated with changes in the main enzymes responsible for cholesterol metabolism. The growth rates of animals were similar when dietary lipid level was 12%. However, a 25% protein/20% fat (25/20) diet produced a decrease in the weight gain when compared with that observed after feeding a 30/20 diet. At low fat level (12%), the decrease in dietary protein produced a little but significant increase in total cholesterol, mainly due to the esterified form. On the contrary, a 25/20 diet produced a lower cholesterol accumulation than that a 30/20 diet. These results suggest that a minimal protein level was required for an optimal utilization of dietary fat for cholesterol deposition in liver. No significant differences were found in 3-hydroxy-3-methylglutaryl-CoA reductase, mevalonate kinase, mevalonate 5-phosphate kinase and mevalonate 5-pyrophosphate decarboxylase when compared the effect of 40/12 and 30/12 diets as well as that of 30/20 and 25/20 diets, suggesting that differences in hepatic cholesterol content were not due to differences in cholesterol synthesis but in the transport to the liver. Changes in the esterified cholesterol were parallel to those found in acyl-CoA: cholesterol acyltransferase, corroborating the main role of this enzyme in the regulation of hepatic cholesterol esterification. |
| Influence of psyllium preparations on plasma and liver lipids of cholesterol-fed rats Kritchevsky, D., S. A. Tepper, et al. (1995), Artery 21(6): 303-11. Abstract: Rats were fed a semi purified diet containing 0.5% cholesterol and 10% fiber (cellulose, pectin, psyllium seed and defatted psyllium husk). One additional group of rats was fed cholesterol (0.5%) as part of a fiber-free diet and another was fed the fiber free diet without cholesterol. Cellulose had virtually no effect on serum or liver lipids. Pectin had a lipid lowering effect. Psyllium seed exerted an effect on total serum cholesterol equal to that of pectin but gave higher levels of HDL-cholesterol. The effects of psyllium seed on liver lipids were more pronounced than those of pectin. Defatted psyllium husk feeding virtually normalized liver size and serum triglyceride levels and produced lower serum total cholesterol levels and higher HDL-cholesterol than observed in normal controls. Defatted psyllium husk feeding also yielded liver lipid values which were in the normal range. Fecal wet and dry weights were significantly higher in rats fed either psyllium preparation. |
| Influence of rapeseed meal, whole rapeseed, and soybean meal on fatty acid composition and cholesterol content of muscle and adipose tissue from ram lambs Solomon, M. B., G. P. Lynch, et al. (1991), J Anim Sci 69(10): 4055-61. Abstract: Twenty-four Suffolk x Hampshire ram lambs (average 46 kg) were assigned to one of three diets containing rapeseed meal (RM), soybean meal (SBM), or whole rapeseed-soybean meal (RSSBM) as the protein source. Diets contained 75% roughage, 14% CP and 2.0 Mcal of ME/kg and lambs were allowed ad libitum access to diets for 35 d. Lipid composition of the longissimus, semimembranosus, and triceps brachii muscles and their corresponding s.c. adipose tissue was determined by gas-liquid chromatography (GLC). The total lipid content in either muscle or subcutaneous fat was not different (P greater than.01) by diet. In lean tissue, palmitic and palmitoleic acids were higher and stearic acid was lower (P less than.01) in rams fed RM than in rams fed RSSBM or SBM, regardless of anatomical location. In the s.c. adipose tissue, the amounts of myristoleic, pentadecylic, and palmitoleic acids were lower and the amount of stearic acid was higher (P less than.01) in rams fed RSSM than in those fed RM or SBM, regardless of anatomical location. The semimembranosus and triceps brachii muscles from all treatments contained 12 to 19% more polyunsaturated fatty acids (PUFA) than the longissimus muscle. The cholesterol content of the three muscles was highest in SBM-fed lambs, lowest in RM-fed lambs, and intermediate in RSSBM-fed lambs. These results demonstrate that dietary treatments of the types used in the present study elicit changes in fatty acid composition of both adipose and muscle tissue without affecting the quantity of total lipid.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Influence of rifampin on serum markers of cholesterol and bile acid synthesis in men Lutjohann, D., C. Hahn, et al. (2004), Int J Clin Pharmacol Ther 42(6): 307-13. Abstract: OBJECTIVE: It has been demonstrated in preliminary studies that rifampin, a semisynthetic antibiotic and known inducer of hepatic cytochrome P450 3A4, reduces serum concentrations of total bile acids only in individuals with liver disease and elevated serum bile acid levels. METHODS: We studied the effect of rifampin on concentrations of surrogate serum markers of cholesterol and bile acid synthesis as well as of cholesterol absorption in 10 male subjects before and after administration of rifampin (600 mg/day) for 6 days. Cholesterol and its precursors were analyzed by gas-liquid chromatography (GLC), bile acid intermediates and individual bile acids by isotope-dilution methods using GLC-mass spectrometry (MS) or by high-performance liquid chromatography (HPLC). RESULTS: Treatment with rifampin resulted in a 70% increase (p = 0.008) of the serum concentration of the bile acid precursor 7alpha-hydroxy-4-cholesten-3-one, which is a marker for bile acid production. Serum total cholesterol was not altered, however, treatment with rifampin elevated the ratio of lathosterol to cholesterol, an indicator of cholesterol synthesis, by 23% (p = 0.037). Interestingly, serum concentration of total bile acids decreased slightly by 29% (p = 0.022), mainly due to a lowering of the secondary bile acid, deoxycholic acid (-60%; p = 0.005). CONCLUSION: A 6-day treatment with rifampin induces a reduction of deoxycholic serum concentrations in healthy men associated with a moderate increase of serum markers of bile acid and endogenous cholesterol synthesis. |
| Influence of risk factors on peripheral and cerebrovascular disease in men with coronary artery disease, low high-density lipoprotein cholesterol levels, and desirable low-density lipoprotein cholesterol levels. HIT Investigators. Department of Veterans Affairs HDL Intervention Trial Papademetriou, V., P. Narayan, et al. (1998), Am Heart J 136(4 Pt 1): 734-40. Abstract: BACKGROUND: The Veterans Administration-HDL Intervention Trial is an ongoing, 20-center, randomized, double-blind, placebo-controlled study aiming to assess the effect of gemfibrozil-improved low high-density lipoprotein cholesterol levels on cardiovascular morbidity and mortality rates. METHODS AND RESULTS: Eligible patients were men with low high-density lipoprotein cholesterol levels and demonstrable coronary heart disease. A total of 2531 patients (average age 63.5 years) were randomly assigned in this study, with a mean high-density lipoprotein cholesterol level of 0.83 mmol/L (32 mg/dL) and low-density lipoprotein cholesterol level of 2.87 mmol/L (111 mg/dL). Baseline data provided the opportunity to assess the interaction of several coronary heart disease risk factors and comorbid vascular diseases. Of these patients, 206 had diabetes mellitus (DM) alone, 1021 had hypertension (HTN) alone, 421 had both DM and HTN, and 883 had neither ("others"). Considering the influence of these risk factors on comorbidities independent of smoking status, patients with DM alone had a 2-fold increase in the prevalence of peripheral vascular disease and a 1.5-fold increase in congestive heart failure. Patients with HTN had a significant increase in the prevalence of cerebrovascular disease, stroke, and congestive heart failure. Patients with HTN and DM had a significant increase in all comorbidities. Smoking resulted in substantial increase of both peripheral vascular disease and cerebrovascular disease. Compared with nonsmoking patients with no DM or HTN, patients with DM and HTN and smoking had a 3-fold increase in the prevalence of peripheral vascular disease and a 3.5-fold increase in cerebrovascular disease (P <.001). CONCLUSIONS: We conclude that DM is a strong correlate of peripheral vascular disease, hypertension of cerebrovascular disease, and that there is a strong additive effect between DM, HTN, and smoking on both. |
| Influence of serum amyloid A on the decrease of high density lipoprotein-cholesterol in active sarcoidosis Salazar, A., J. Mana, et al. (2000), Atherosclerosis 152(2): 497-502. Abstract: OBJECTIVE: We have previously observed low levels of high density lipoprotein (HDL) cholesterol in active sarcoidosis. The aim of this study was to analyze the role of serum amyloid A (SAA) on this lipid disorder. METHODS: Eighty five untreated sarcoid patients, 40 with active disease and 45 with inactive disease, were recruited. Sarcoidosis activity was evaluated by means of clinical, chest X-ray, gallium-67 scan, serum angiotensin converting enzyme (peptidyl-dipeptidase A) values, and pulmonary function tests. Analysis of lipoprotein metabolism included: serum cholesterol, low density lipoprotein (LDL)-cholesterol, HDL-cholesterol, HDL(2)-cholesterol, HDL(3)-cholesterol, apolipoprotein A-I (apo A-I), apolipoprotein B (apo B), and triglyceride concentrations. Serum amyloid A protein and lecithin-cholesterol acyltransferase (LCAT) activity were measured. RESULTS: In active sarcoidosis we found significantly reduced levels of HDL-cholesterol (1.17+/-0.36 vs. 1. 44+/-0.39 mmol/l, P=0.002), HDL(3)-cholesterol (0.78+/-0.23 vs. 1. 02+/-0.21 mmol/l, P<0.0001), and apo A-I (1.36+/-0.29 vs. 1.61+/-0. 27 g/l, P<0.0001) and significantly increased levels of triglyceride (1.51+/-0.64 vs. 1.03+/-0.46 mmol/l, P<0.0001), and apo B (1.14+/-0. 25 vs. 0.99+/-0.27 g/l, P=0.012) versus inactive sarcoidosis. Serum amyloid A concentrations were significantly increased in the patients with active disease (155.45+/-154.01 mg/ml) compared to the inactive sarcoid patients (89.70+/-65.36 mg/ml) (P=0.011). There were no significant differences in cholesterol, LDL-cholesterol, HDL(2)-cholesterol or LCAT values between groups. Multivariate logistic regression analysis showed that HDL-cholesterol (regression coefficient b=-1.96; S.E.=0.87; P=0.02) and SAA (regression coefficient b=0.01; S.E.=0.004; P=0.01) were the two variables independently associated with disease activity. Moreover, a significant negative correlation was observed between SAA levels and both HDL-cholesterol (r=-0.39; P=0.01) and apo A-I (r=-0.35; P=0.03) levels, in the active sarcoid group. Conversely, no correlation was found in the inactive sarcoid group. CONCLUSION: The low HDL-cholesterol and apo A-I concentrations seen in active sarcoid patients are associated with a significant increase of SAA levels. We suggest that the displacement of apo A-I by SAA on HDL accounts for the lower level of HDL-cholesterol seen in active sarcoidosis. |
| Influence of serum cholesterol and cholesterol subfractions on restenosis after successful coronary angioplasty. A quantitative angiographic analysis of 3336 lesions Violaris, A. G., R. Melkert, et al. (1994), Circulation 90(5): 2267-79. Abstract: BACKGROUND--Previous reports have suggested that hyperlipidemia may be associated with increased restenosis after successful coronary angioplasty. These studies have been compromised, however, by their retrospective nature, the small numbers involved, differences in the definition of restenosis, and inadequate quantitative angiographic follow-up at a prespecified time interval. The objective of the study was to examine the relation between serum cholesterol and long-term restenosis after coronary angioplasty, using quantitative angiography, at a predetermined time interval. METHODS AND RESULTS--The study population comprised 2753 patients (3336 lesions) prospectively enrolled and successfully completing four major restenosis trials. Cineangiographic films were processed and analyzed at a central angiographic core laboratory with the use of an automated interpolated edge-detection technique. Serum total cholesterol was measured at trial entry and at 6 months. Hypercholesterolemia was defined as total cholesterol > 7.8 mmol.L-1 at trial entry. Two approaches were used to assess restenosis: first, a categorical approach using the cutoff point of > 50% diameter stenosis at follow-up and second, a continuous approach examining changes in minimal luminal dimensions, the absolute loss (change in minimum luminal diameter after PTCA to follow-up, in mm) and relative loss (absolute loss corrected for vessel size), which may give a better understanding of the underlying pathological process involved. One hundred sixty patients with 191 lesions (5.73%) had hypercholesterolemia (total cholesterol, > 7.8 mmol.L-1; mean +/- SD, 8.46 +/- 0.75 mmol.L-1) and 2593 patients with 3145 lesions (94.27%) normal cholesterol (5.67 +/- 1.06 mmol.L-1). The restenosis rate was similar in patients with and without hypercholesterolemia (31.9% versus 33.7%, respectively; relative risk, 0.975; 95% CI, 0.882 to 1.077; P =.68). Similarly, there was no difference in either the absolute or relative loss between patients with and without hypercholesterolemia (0.31 +/- 0.53 versus 0.32 +/- 0.53 mm and 0.12 +/- 0.20 versus 0.13 +/- 0.21, respectively, P = NS for both). Conversely, the total serum cholesterol in patients with restenosis (using the categorical definition) was similar to those without restenosis (5.84 +/- 1.24 versus 5.81 +/- 1.22 mmol/L, respectively, P = NS). Dividing the population into deciles according to total cholesterol and examining the categorical restenosis rate (by chi 2) as well as the absolute and relative loss by ANOVA again revealed no significant differences between deciles. Subgroup analysis of 579 patients (667 lesions) with HDL and LDL cholesterol levels available again revealed no differences in the categorical restenosis rate (by chi 2) or the absolute or relative loss between deciles according to LDL, HDL, or LDL:HDL ratio, suggesting no influence of these cholesterol subfractions on restenosis. CONCLUSIONS--Our results indicate that there is no association between cholesterol and restenosis by either a categorical or continuous approach, suggesting that measures aimed at reducing total cholesterol are unlikely to significantly influence postangioplasty restenosis. |
| Influence of serum cholesterol and cholesterol subfractions on restenosis following successful coronary intervention Violaris, A. G., T. F. Ismail, et al. (1999), Semin Interv Cardiol 4(3): 111-9. |
| Influence of serum cholesterol and other coronary risk factors on vasomotion of angiographically normal coronary arteries Seiler, C., O. M. Hess, et al. (1993), Circulation 88(5 Pt 1): 2139-48. Abstract: BACKGROUND. It has been shown that there is impairment of the vasodilatory response to acetylcholine in patients with hypercholesterolemia and angiographically normal coronary arteries. Moreover, in patients with angiographically smooth coronary arteries, the number of coronary risk factors is associated with a loss of endothelium-dependent vasodilation. The purpose of the present analysis was to evaluate in patients with and without coronary artery disease coronary vasomotor response to dynamic exercise in angiographically normal and stenosed coronary arteries and to relate the response to serum cholesterol levels as well as to other coronary risk factors. METHODS AND RESULTS. Luminal area change during exercise (delta-ex, percent change compared with rest = 100%) was determined by biplane quantitative coronary arteriography in three groups: Group 1 consisted of 14 patients with normal total serum cholesterol of < 200 mg/100 mL; mean, 173 mg/100 mL (mean age, 51 years). Group 2 comprised 23 patients with a slightly elevated cholesterol of 200 to 250 mg/100 mL; mean, 223 mg/100 mL (mean age, 53 years). Group 3 had 24 patients with markedly elevated cholesterol of > 250 mg/100 mL; mean, 288 mg/100 mL (mean age, 54 years). Serum cholesterol levels and categorical risk factors such as positive family history, history of hypertension, smoking, obesity, and diabetes were related to exercise-induced vasomotor response. The three groups did not differ with regard to clinical characteristics, exercise work load, and hemodynamic data measured during exercise. However, delta-ex in normal vessels was significantly different between all three groups (ANOVA, P <.01): +31% (group 1), +18% (group 2), and +4% (group 3). Delta-ex in stenotic vessels did not differ between the groups: -5% (group 1), -13% (group 2), and -12% (group 3). Delta-ex of the nonstenosed vessel correlated significantly and inversely with total cholesterol, with low-density lipoprotein cholesterol, with the ratio of total to high-density lipoprotein cholesterol, and with the number of coronary risk factors present in a patient. High total cholesterol and a history of hypertension were independent risk factors for impaired coronary vasomotion. CONCLUSIONS. In patients with and without coronary artery disease, hypercholesterolemia and a history of hypertension independently impair exercise-induced coronary vasodilation in angiographically normal coronary arteries. In the stenotic vessel, vasomotion during exercise does not appear to be influenced by the actual serum cholesterol. The precise mechanism by which the impaired vasomotion of the angiographically normal coronary arteries is mediated is unknown, but a direct negative effect of hypercholesterolemia on endothelial function or early undetected atherosclerosis appears to be the most likely explanation. |
| Influence of serum cholesterol on atherogenesis and intimal hyperplasia after angioplasty: inhibition by amlodipine Kahn, M. B., K. Boesze-Battaglia, et al. (2005), Am J Physiol Heart Circ Physiol 288(2): H591-600. Abstract: The objectives of the present study were to determine whether serum hypercholesterolemia (HC) promotes the development of spontaneous and angioplasty-induced lesions and whether amlodipine inhibits these lesions and cellular processes underlying their genesis. Rabbits were fed normal, 0.5%, or 2% cholesterol diets for 9 wk, which resulted in the development of increasing HC. After week one, balloon dilation of the abdominal aorta was performed while the thoracic aorta was not disturbed and monitored for the development of spontaneous lesions. Lesion size increased with the degree of HC and was accompanied by increased collagen synthesis and smooth muscle cell (SMC) proliferation at each site. Amlodipine (5 mg/kg p.o.) inhibited lesion size by 50% (P < 0.01) at both sites in cholesterol-fed animals but not at angioplasty sites in animals on a normal diet. Local collagen synthesis was inhibited at both sites by amlodipine in the diet animals. The increase in HC was accompanied by a 1.7-fold increase in basal Ca2+ uptake in SMCs in the thoracic aorta, which was not altered by amlodipine, nifedipine, Ni2+, or La3+, revealing an uninhibitable calcium leak during atherogenesis. In culture, cholesterol enrichment increased SMC proliferation, collagen synthesis, and the secretion of a soluble SMC mitogen, which were inhibited by amlodipine (10(-9) M). Finally, in SMC membranes, amlodipine uniquely restored the cholesterol-expanded membrane bilayer width without any effect on membrane fluidity. This study establishes a causal role between serum HC and the development of spontaneous and angioplasty-induced lesions and the ability of amlodipine to disrupt this action by a novel remodelling action on the SMC membrane. |
| Influence of serum triglyceride levels on the risk for myocardial infarction in 12,510 middle aged males: interaction with serum cholesterol Stavenow, L. and T. Kjellstrom (1999), Atherosclerosis 147(2): 243-7. Abstract: OBJECTIVE: To study the influence of different levels of serum (s)-triglycerides in relation to s-cholesterol on the risk of myocardial infarction. DESIGN AND SUBJECTS: A 6-13 (mean 10) year follow-up of 12,510 middle-aged men. Fasting s-triglycerides and s-cholesterol were measured at the screening examination. SETTING: Section of Preventive Medicine at the Department of Internal Medicine, Malmo General Hospital, an urban hospital for 240,000 inhabitants in southern Sweden. INTERVENTION: In minor groups of patients there were interventions addressing high lipid levels, high alcohol consumption, hypertension and glucose intolerance. MAIN OUTCOME MEASURE: Myocardial infarction was used as an end-point. RESULTS: 446 myocardial infarctions occurred. The cumulative incidence rates were for the lowest triglyceride quartile 1.2%, for the second 3.2%, for the third 4.1% and for the highest 5.6%. After adjustment for age, year of screening, body mass index, diabetes, smoking, hypertension and s-cholesterol there was a significant relationship between triglycerides and the relative risk for myocardial infarction (P for trend=0.0087). For increasing levels of triglycerides, adjusted for the above factors except cholesterol, the impact of a certain cholesterol value for the occurrence of myocardial infarction was increased (P for trend=0.0092). CONCLUSIONS: The present study emphasizes the interaction between cholesterol and triglyceride values for the risk of myocardial infarction. It is concluded that at triglyceride values above 1.0 mmol/l and cholesterol above 6.8 mmol/l there is an increasing interaction between cholesterol and triglyceride levels that might be of importance when evaluating the cardiovascular risk of middle aged men. |
| Influence of sex and diet on quantitative trait loci for HDL cholesterol levels in an SM/J by NZB/BlNJ intercross population Korstanje, R., R. Li, et al. (2004), J Lipid Res 45(5): 881-8. Abstract: To investigate the dependence of HDL quantitative trait loci (QTL) on sex and diet, we generated a large intercross population of mice from parental strains SM/J and NZB/BlNJ. We measured HDL levels in progeny fed a chow diet and measured them again after 6, 12, and 16 weeks of feeding a high-fat, high-cholesterol diet. QTL analysis was performed on the 260 female and 253 male F(2) progeny. A total of 13 significant QTL were found. Four QTL were specific to female mice: Hdlq23 (Chr 6, 26 cM), Hdlq26 (Chr 10, 70 cM), Hdlq27 (Chr 15, 48 cM), and Hdlq32 (Chr 19, 40 cM). One significant QTL was specific to male mice: Hdlq29 (Chr 17, 36 cM). In addition, several QTL were found to have effects that were dependent on diet. Sex- and diet-dependent effects were characterized using a linear model-based genome scan method that avoids the potential pitfalls of subdivided data analysis. The dependence of QTL effects on sex suggests an important role for the sex hormones in HDL regulation. We recommend that sex should be explicitly accounted for in future studies in the genetics of HDL regulation in both mice and humans. |
| Influence of sex and glucocorticoid hormones on 3H cholesterol uptake in the aortic wall and 3H adrenaline in the brain Burtea, C., C. Murgiuc, et al. (1991), Endocrinologie 29(3-4): 137-45. Abstract: The mechanisms involved in the atherogenesis process and the connection of the latter with stress were studied, by trying to elucidate the difference in the response of the two sexes to the causative factors. To this purpose, the role of the sex hormones (testosterone, estradiol, progesterone) and glucocorticoids (hydrocortisone hemisuccinate) in 3H cholesterol uptake in the aortic wall and 3H adrenaline in the brain was investigated. In males, the results show that these hormones favoured the uptake of the two markers whose level was significantly raised (p greater than 0.05; p greater than 0.01) as against the controls all along the 20 days of treatment. In females, the level of 3H cholesterol in the aorta and 3H adrenaline in the brain had a statistical significance (p greater than 0.05) only in the first days of treatment but after the 6th day it began to decline. |
| Influence of short term dietary cholesterol and fat on human plasma Lpa and LDL levels Brown, S. A., J. Morrisett, et al. (1991), J Lipid Res 32(8): 1281-9. Abstract: The relationship between plasma levels of Lpa and LDL was examined using dietary regimens. In 81 normolipidemic male outpatients, dietary cholesterol was increased by consuming six eggs per day from a mean (SD) level of 311 (162) to 1430 (198) mg per day. Mean (SD) LDL-cholesterol levels increased from 102 (26) mg/dl to 120 (33) mg/dl (P less than 0.001), while mean (SD) Lpa levels were 5.5 (6.1) mg/dl on the basal diet and 5.6 (6.4) mg/dl on the cholesterol-rich diet. No significant correlation was observed between increases in either LDL-cholesterol or apolipoprotein B to Lpa, nor was there any relationship between individual baseline levels of Lpa and dietary-induced changes of Lpa. Fourteen of the 81 participants were reexamined under strict nutritional control. Four diets with 40% of calories as fat, but differing in the type of fat and the amount of cholesterol, were administered sequentially to all subjects. As expected, mean (SD) LDL-cholesterol and apolipoprotein B levels were highest on the saturated fat, high cholesterol diet (112 (32) mg/dl and 79 (22) mg/dl) and lowest on the polyunsaturated fat, low cholesterol diet (77 (27) mg/dl and 53 (18) mg/dl). In contrast, mean Lpa levels did not significantly change among the four diets (range 4.2-4.9 mg/dl). No correlation of Lpa responses with changes in plasma lipids, apolipoproteins, or lipoproteins was observed on any diet. These data suggest that determinants of plasma Lpa levels are distinctly different from the determinants of plasma LDL levels in normolipidemic males. |
| Influence of sire growth potential, time on feed, and growing-finishing strategy on cholesterol and fatty acids of the ground carcass and longissimus muscle of beef steers Rule, D. C., M. D. MacNeil, et al. (1997), J Anim Sci 75(6): 1525-33. Abstract: The purpose of this study was to determine how diverse beef cattle production systems affect fatty acids and cholesterol of meat. Crossbred cows were bred by AI to high (H) or moderate (M) growth rate potential bulls to produce spring- or fall-born calves. Steer calves from these matings were placed on finishing diets at three ages. Spring-born steers were started at 6 or 18 mo of age (A6 and A18), and fall-born calves were started at 12 mo of age (A12). Slaughter times were 0, 90, 180, and 270 d for A6; 68, 136, and 204 d for A12; and 0, 45, 90, and 135 d for A18. Four steers of each type were slaughtered in each of 2 yr for each sire type x time on feed x slaughter group. Fatty acids and cholesterol of ground carcass and longissimus muscle (LM) were determined by GLC. Carcass fat increased faster in M than in H steers (P <.01). Ground carcass cholesterol was greater for M steers (P =.06) than for H steers because of the greater fat content in the M ground carcass. No differences in LM cholesterol were observed for sire growth potential or time on feed. Fatty acid differences in ground carcass with time on feed were due primarily to decreases in 18:0 and increases in 18:1. The LM saturated and monounsaturated fatty acids changed little with time on feed, but total saturates were greater for M steers (44.5%) than for H steers (42.8%) (P =.02). A18 steers of H sires had the greatest (P =.04) ratio of 18:0 plus unsaturates to 14:0 plus 16:0 (most hypocholesterolemic). We conclude that cholesterol in lean muscle is not altered by the sire growth potential x time on feed x growing-finishing strategy imposed, and that lean beef from steers sired by H bulls and backgrounded before finishing may produce meat with the healthiest lipid composition. |
| Influence of smoking on cholesterol concentrations in serum lipo-protein of healthy subjects Zhang, Y. (1992), Zhonghua Liu Xing Bing Xue Za Zhi 13(2): 97-100. Abstract: Sixty hundred and nineteen-seven smokers and 841 non-smokers among healthy male workers of 40-60 years of age were comparatively observed. Their housing environment and working conditions were similar. The results showed that smoking had remarkable influence on the cholesterol concentration in the serum lipo-protein of healthy subjects. The levels of HDL-C HDL2-C, HDL3-C and HDL2-C/HDL3-C of the smoking group were obviously lower than those of the non-smoking group, while the levels of LDL-C, VLDL-C and LDL-C/HDL-C of the smoking group were obviously higher than those of the non-smoking group. Moreover, these indices were significantly associated with the smoking amount, smoking duration, depth of inhalation. Smoking was an important dangerous factor for lowering levels of HDL-C, HDL2-C, HDL 3-C, HDL2-C/HDL3-C and raising levels of LDL-C, VLDL-C, LDL-C/HDL-C. The relative risk (RR) of the two factors were estimated to be 1.09-5.77 and 2.37-3.57 respectively. The levels of the 7 indices such as HDL-C of passive smokers were identical with those of light smokers. This showed that passive smoking also had marked influence on cholesterol concentrations in serum lipoprotein. |
| Influence of stearic acid on cholesterol metabolism relative to other long-chain fatty acids Grundy, S. M. (1994), Am J Clin Nutr 60(6 Suppl): 986S-990S. Abstract: Stearic acid is a long-chain saturated fatty acid. However, in contrast with other saturated fatty acids, stearic acid apparently does not raise serum cholesterol concentrations. Studies carried out three decades ago provided strong suggestive evidence that this was the case. More recent investigations that specifically compared stearic acid with other fatty acids in human studies have confirmed that stearic acid is not hypercholesterolemic. Stearic acid was shown not to raise low-density-lipoprotein cholesterol relative to oleic acid, which is known to be neutral in its effects on cholesterol concentrations. In contrast, palmitic acid, another long-chain saturated fatty acid, definitely raises cholesterol concentrations. For this reason, fats rich in stearic acid might be used in place of those high in palmitic acid in cholesterol-lowering diets. |
| Influence of stigmastanol and stigmastanyl-phosphorylcholine, two plasma cholesterol lowering substances, on synthetic phospholipid membranes. A 2H- and 31P-NMR study Habiger, R. G., J. M. Cassal, et al. (1992), Biochim Biophys Acta 1103(1): 69-76. Abstract: Cholesterol, stigmastanol, and stigmastanyl-phosphorylcholine (ST-PC) were incorporated into model membranes composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). POPC and ST-PC were deuterated at the lipid headgroup, DOPC at the cis-double bonds. The influence of the three sterols on the motion and conformation of the lipid headgroups and the hydrocarbon chains was monitored with 2H- and 31P-NMR. All three sterols were freely miscible with the lipid matrix in concentrations of up to 50 mol% without inducing phase separations or nonbilayer structures. However, the molecules exert quite different effects on the phospholipid bilayer. Cholesterol and stigmastanol are largely buried in the hydrocarbon part of the membrane, distinctly restricting the flexing motions of the fatty acyl chains whereas the conformation of the phospholipid headgroups is little affected. In contrast, ST-PC is anchored with its headgroup in the layer of phospholipid dipoles, preventing an extensive penetration of the sterol ring into the hydrocarbon layer. Hence ST-PC has almost no effect on the hydrocarbon chains but induces a characteristic conformational change of the phospholipid headgroups. The 2H- and 31P-NMR spectra of mixed phospholipid/ST-PC membranes further demonstrate that the PC headgroup of ST-PC has a similar orientation as the surrounding phosphatidylcholine headgroups. For both types of molecules the -P-N+ dipole is essentially parallel to the membrane surface. Addition of ST-PC induces a small rotation of the POPC headgroup towards the water phase. |