| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Postdischarge lipid management of coronary artery disease patients according to the new National Cholesterol Education Program guidelines Hunninghake, D. B. (2001), Am J Cardiol 88(8A): 37K-41K. Abstract: The highest risk of a recurrent event in patients with acute coronary syndromes (ACS) occurs in the first month, with the rates of reported events ranging from 10% to 25%. Statins are the cornerstone of lipid-lowering therapy for the long-term care of patients with stable atherosclerotic disease. More recent accumulated data from several trials now show that statin therapy can also help reduce cardiovascular risk in unstable disease. These studies evaluated the effects of statin therapy begun before discharge, with the Myocardial Ischemia with Aggressive Cholesterol Lowering (MIRACL) trial showing that therapy could be started as early as 24 hours after onset with measurable clinical benefit. Registry data also suggest that long-term compliance may be improved in patients with a predischarge statin prescription compared with a postdischarge statin prescription. This is because many patients discharged without a statin prescription are either lost to further medical follow-up or do not receive a statin prescription from their primary care provider. The Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III), which constitutes the updated clinical guidelines of the National Cholesterol Education Program (NCEP), recommends that lipid-lowering drug therapy be initiated at hospital discharge. ATP III also provides important information on the goals of lipid-lowering therapy in patients after ACS. The challenge for the specialist is to establish a predischarge plan that includes maximal dosing to achieve aggressive target goals and to work with the patient's primary care provider to maintain these goals long-term. |
| Postnatal development of plasma-lipid-clearing enzymes (lipoprotein lipase, hepatic lipase and lecithin:cholesterol acyl transferase) and lipid profiles in suckling rats Mao, J. and M. Hamosh (1992), Biol Neonate 62(1): 1-9. Abstract: We examined the activity of plasma circulating lipoprotein lipase and hepatic lipase, lecithin:cholesterol acyl transferase (LCAT), as well as lipid profiles in Sprague-Dawley rats from 1 day until 29 days of age. Plasma lipoprotein lipase activity peaked between ages 5 and 15 days and decreased after weaning, while plasma hepatic lipase activity remained constantly low during the suckling period and increased after weaning. No statistically significant difference in LCAT activity was seen from birth until weaning. Plasma triglycerides, as well as free fatty acids, decreased significantly after birth. Total plasma cholesterol increased during the suckling period and decreased after weaning. HDL cholesterol increased after the first 10 days of life, and free cholesterol remained constant after an initial decrease from birth to the 5th day of life. In conclusion, the enzymes associated with the metabolism of triglycerides, cholesterols and phospholipids are well developed in the rat shortly after birth. |
| Postoperative cholesterol cyst of the mastoid Bizakis, J., A. Pagalos, et al. (2000), Otolaryngol Head Neck Surg 122(2): 312. |
| Postoperative cholesterol cysts of the mastoid Saito, T., T. Ohtsubo, et al. (1996), Ann Otol Rhinol Laryngol 105(11): 922-5. |
| Postoperative reduction of high serum cholesterol concentrations and experimental vein bypass grafts. Effect on the development of intimal hyperplasia and abnormal vasomotor function Klyachkin, M. L., M. G. Davies, et al. (1994), J Thorac Cardiovasc Surg 108(3): 556-66. Abstract: Hypercholesterolemia is an important contributor to the development of intimal hyperplasia and superimposed accelerated atherosclerosis in vein bypass grafts. This study examines the effect of dietary modification of serum cholesterol on the development of intimal hyperplasia and vasomotor function of vein grafts. Thirty male New Zealand White rabbits had a right carotid vein bypass graft and were put to death 28 days after the operation. Twenty animals received a 1% cholesterol diet for 4 weeks before the operation. In 10 animals this diet was continued until harvest (hypercholesterolemia group). In another 10 animals the diet was changed to standard rabbit chow on the day of the surgical procedure and continued until harvest (cholesterol reduction group). The last 10 animals were control subjects. Vein grafts were harvested either for histologic study or for in vitro isometric tension studies. Cumulative dose response curves to norepinephrine, serotonin, bradykinin, and endothelin-1 were determined. After in situ pressure fixation, intimal thicknesses of the vein grafts were measured by videomorphometry. The change in diet produced a 74% reduction in serum cholesterol concentration within 28 days. There was a 26% reduction in the intimal thickness of vein graft intimal hyperplasia and the macroscopic disappearance of atheromatous lesions from the graft wall, which are always observed in vein grafts from the hypercholesterolemia group. Cholesterol reduction did not change hypercholesterolemia-induced agonist supersensitivity. Therefore, cholesterol reduction slows the formation of intimal hyperplasia in vein grafts but does not prevent the persistence of the hypercholesterolemia-associated smooth muscle phenotype. |
| Postprandial appearance of dietary deuterated cholesterol in the chylomicron fraction and whole plasma in healthy subjects Dubois, C., M. Armand, et al. (1996), Am J Clin Nutr 64(1): 47-52. Abstract: This study examined the appearance of dietary cholesterol in the chylomicron fraction (chylomicrons plus chylomicron remnants) and whole plasma in healthy normolipidemic subjects during a 0-7-h postprandial period. Six adult males were given two diet sequences in random order: a low-fiber diet (standard Western diet for 14 d) followed by a labeled low-fiber test meal or a fiber-supplemented diet (40 g oat bran/d for 14 d) followed by a labeled oat bran (40 g) test meal. The test meals provided 192.5 mg cholesterol, including 80.1 mg octadeuterated cholesterol. Fasting and hourly postmeal blood samples were obtained for 7 h. Isotopic cholesterol ratios tracer:(tracer+native cholesterol) were determined by gas chromatography-mass spectrometry. Chylomicron triacylglycerol and cholesterol concentrations peaked after 2-3 h and returned to baseline after 7 h. After the low-fiber test meal, the isotopic cholesterol ratio continuously increased until 7 h in the chylomicron fraction (4.2 +/- 1.2 x 10(-3)) and whole plasma (1.04 +/- 0.39 x 10(-3)). At 7 h postprandial, the maximum dietary cholesterol concentration in the chylomicron fraction and plasma cholesterol was 1 in 99 and 1 in 397 cholesterol molecules, respectively. No marked differences were obtained after the high-fiber sequence compared with the low-fiber one; there was a comparable isotopic cholesterol ratio and concentration in the chylomicron fraction and a slightly lower (-44%, P < 0.10) 0-7 h area under the curve whole-plasma deuterated cholesterol concentration. Thus, dietary cholesterol supplied as a single meal does not simultaneously appear in the chylomicron fraction postprandially with endogenous cholesterol and triacylglycerols and fiber feeding does not markedly alter this process in healthy normolipidemic humans. |
| Postprandial chylomicrons: potent vehicles for transporting cholesterol from endogenous LDL+HDL and cell membranes to the liver via LCAT and CETP Chung, B. H., P. Liang, et al. (2004), J Lipid Res 45(7): 1242-55. Abstract: We examined whether postprandial (PP) chylomicrons (CMs) can serve as vehicles for transporting cholesterol from endogenous cholesterol-rich lipoprotein (LDL+HDL) fractions and cell membranes to the liver via lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities. During incubation of fresh fasting and PP plasma containing (3)Hcholesteryl ester (CE)-labeled LDL+HDL, both CMs and VLDL served as acceptors of (3)HCE or cholesterol from LDL+HDL. The presence of CMs in PP plasma suppressed the ability of VLDL to accept (3)HCE from LDL+HDL. In reconstituted plasma containing an equivalent amount of triglycerides from isolated VLDL or CMs, a CM particle was about 40 times more potent than a VLDL particle in accepting (3)HCE or cholesterol from LDL+HDLs. When incubated with red blood cells (RBCs) as a source for cell membrane cholesterol, the cholesterol content of CMs, VLDL, LDL, and HDL in PP plasma increased by 485%, 74%, 13%, and 30%, respectively, via LCAT and CETP activities. The presence of CMs in plasma suppressed the ability of endogenous lipoproteins to accept cholesterol from RBCs. Our data suggest that PP CMs may play an important role in promoting reverse cholesterol transport in vivo by serving as the preferred ultimate vehicle for transporting cholesterol released from cell membranes to the liver via LCAT and CETP. |
| Postprandial decrease in HDL cholesterol and HDL apo A-I in normal subjects in relation to triglyceride metabolism De Bruin, T. W., C. B. Brouwer, et al. (1991), Am J Physiol 260(3 Pt 1): E492-8. Abstract: The postprandial lipoprotein metabolism is important since it determines the circulation of potentially atherogenic particles and influences the metabolism of high-density lipoproteins (HDL) in a complex manner that is at present not completely understood. Therefore, the short-term (24-h) changes in postprandial lipoprotein metabolism, including retinyl palmitate (RP), apolipoprotein A-I (apo A-I), and apolipoprotein B, were studied in relation to postheparin lipolytic activities in six healthy normolipidemic men after an oral RP fat tolerance test. The fat load (98 g) was cleared in 7 h, because the triglyceride (TG) concentrations had returned to initial values (0.72 +/- 0.31 mmol/l) at that time. RP showed a peak in plasma at 4 and 5 h but remained present in chylomicron (remnants) in low concentrations after 8 and 24 h. After the fat load, HDL cholesterol and HDL-associated apo A-I showed a significant decrease in concentration of 35 and 29%, respectively. The decrease coincided with the increase in chylomicron remnants and the transient appearance of TG-enriched HDL. Hepatic lipase was correlated to both the initial HDL cholesterol concentration as well as the peak concentration of TG in chylomicron remnants, suggesting that it could be one of the regulating common physiological pathways in postprandial HDL and TG metabolism. In the subjects studied, the atherogenic potential of plasma increased in response to an oral fat load, characterized by a decrease in HDL cholesterol and HDL-associated apo A-I. |
| Postprandial effect of a high fat meal on plasma lipid, lipoprotein cholesterol and apolipoprotein measurements Rifai, N., J. R. Merrill, et al. (1990), Ann Clin Biochem 27 (Pt 5): 489-93. Abstract: We investigated the effect of a fatty meal on plasma concentrations of lipids, apolipoproteins, and the cholesterol component of lipoproteins. Sixteen nonobese, healthy, asymptomatic males, 22-34 years of age, served as subjects for this study. None smoked, consumed more than two alcoholic drinks per day, or took any medication known to alter plasma lipids. After a 12 h fast, baseline plasma samples were obtained just before subjects consumed a high fat meal. The meal, standardized to a 70 kg individual, contained approximately 70 g fat, 580 mg cholesterol, and 1,100 cal, with 56% of the calories coming from fat. During the 8 h following consumption of the meal, subjects rested quietly and consumed no food or beverages except water. Blood specimens were obtained hourly. There was a significant increase in plasma triglyceride (150% from baseline at 3 h, P less than 0.0005). Very low density lipoprotein cholesterol (VLDL-C) concentrations increased 150% at 3 h (P less than 0.0005) while low density lipoprotein cholesterol (LDL-C) concentration decreased 37% at 3 h (P less than 0.005) when estimated by Friedewald's formula. No statistically significant differences were observed between fasting total cholesterol, high density lipoprotein cholesterol (HDL-C). HDL2-C, and HDL3-C, apolipoprotein AI (apo AI, AII), and B-100 concentrations and non-fasting samples. We conclude that plasma triglyceride concentration is significantly affected in the post-prandial state. As a result, VLDL-C and LDL-C when assessed by the Friedewald formula are also altered. A minimum of 8 h fasting is required to assess these concentrations accurately in this population.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Postprandial hyperlipidemia in streptozotocin-induced diabetic rats is due to abnormal increase in intestinal acyl coenzyme A:cholesterol acyltransferase activity Kusunoki, J., K. Aragane, et al. (2000), Arterioscler Thromb Vasc Biol 20(1): 171-8. Abstract: Postprandial hyperlipidemia (PH) is recognized as a significant risk factor for cardiovascular disease. The present study, involving rats with streptozotocin (STZ)-induced diabetes, was performed to establish a PH model and to examine the relation between small intestinal acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity and serum lipid levels in the postprandial state. The small intestinal ACAT activities in normal rats during the experimental period were 4 to 5 pmol/mg protein per minute. In contrast, in the diabetic rats, the ACAT activities were 2 to 3 times higher than activities seen in normal rats from 7 to 21 days after the STZ injection in the absence of a high fat diet and hyperplasia in the gut. In an oral fat-loading test that used diabetic rats that had been injected with STZ (60 mg/kg) intravenously 14 days previously, the postloading changes in the serum concentrations of total cholesterol (TC) and triglyceride (TG) were significantly greater in the diabetic rats than in normal rats. Single oral administration of (1s,2s)-2-3-(2,2-dimethylpropyl)-3-nonylureidocyclohexane- 1-yl 3-(4R)-N-(2,2,5,5-tetramethyl-1, 3-dioxane-4-carbonyl)aminopropionate (F-1394, 3 to 30 mg/kg), a potent ACAT inhibitor, suppressed the post-fat-loading elevation of serum TC levels in the diabetic rats in a dose-dependent manner without affecting serum glucose levels. Furthermore, the small intestinal ACAT activity, serum TG levels, and lymphatic absorption of TC and TG in the rats that were administered F-1394 (30 mg/kg) were reduced by approximately 90%, 70%, 30%, and 15%, respectively. This is the first evidence that elevated ACAT activity in the gut, unlike hyperplasia and hyperphagia, induces PH in rats. Our results strongly suggest that F-1394 may be a potential treatment for PH in humans. |
| Postprandial hyperlipidemia in Zucker diabetic fatty fa/fa rats, an animal model of type II diabetes, and its amelioration by acyl-CoA:cholesterol acyltransferase inhibition Fujinami, K., K. Kojima, et al. (2001), Jpn J Pharmacol 86(1): 127-9. Abstract: Postprandial hyperlipidemia (PH) is frequently observed in diabetic patients. We performed an oral fat-loading test in Zucker diabetic fatty (ZDF) fa/fa rats, a model for type II diabetes, to determine whether PH was induced in the rats. Post fat-loading changes in serum cholesterol and triglyceride levels were significantly greater in the fa/fa rats than those seen in their lean littermates and an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor significantly reduced these levels by 24% and 31%, respectively. Therefore, we confirmed that PH appeared in ZDF fa/fa rats by fat loading and ACAT inhibition may be a potential treatment for PH. |
| Postprandial lipaemia is exacerbated in fat-cholesterol-fed rabbits: relationship to atheroma deposition Juhel, C., C. Dubois, et al. (1997), Br J Nutr 78(2): 301-11. Abstract: The aim of the present study was to evaluate the links between chronic fat-cholesterol intake, postprandial lipaemia and atherogenesis in New Zealand White rabbits. Adult rabbits were fed on either a low-fat control diet (LF) or a high-fat, high-cholesterol diet (HF). Rabbits received a test meal containing 3Hcholesterol and 14Ctriolein on days 0 and 63 for the LF group and days 14, 28, 42, 63 and 84 for the HF group. Blood was collected 24 h post-absorptively and 10, 24, 34 and 48 h after test-meal intake. Post-absorptive as well as postprandial lipoproteins and lipaemia were not modified in the LF rabbits, who did not show any atheroma deposition on day 119. In HF rabbits, postprandial plasma triacylglycerols peaked 24-34 h after meal intake. The 0-48 h areas under the curves of triacylglycerol and triacylglycerol-rich lipoproteins (TRL) steadily increased with time of chronic lipid feeding with values significantly higher than those in the LF rabbits. The postprandial plasma and TRL concentrations of dietary radiolabelled lipids were significantly higher in HF than LF rabbits. Post-heparin lipoprotein lipase (EC 3.1.1.34) and hepatic lipase (EC 3.1.1.3) activities were twofold higher in HF rabbits than in LF rabbits at day 105. In HF rabbits, a marked atheroma plaque deposition in the aorta was observed (30.9 (SE 3.9) % of total surface). The extent of atheroma deposition was positively correlated to the postprandial responses of plasma total triacylglycerols and dietary-derived lipids as well as total cholesterol and dietary-derived cholesterol in HF rabbits. In conclusion, chronic ingestion of a HF diet led to marked increases in postprandial lipaemia and TRL particles, and atheroma deposition. |
| Postprandial lipemia under treatment with Allium sativum. Controlled double-blind study of subjects with reduced HDL2-cholesterol Rotzsch, W., V. Richter, et al. (1992), Arzneimittelforschung 42(10): 1223-7. Abstract: Postprandial Lipaemia under Treatment with Allium sativum/Controlled double-blind study in healthy volunteers with reduced HDL2-cholesterol levels. The effectiveness of a standardized garlic powder preparation (Sapec, Kwai) on alimentary hypertriglyceridaemia after intake of a standardized fatty test meal containing 100 g butter was analyzed in a randomized placebo-controlled double-blind study. 24 volunteers with HDL2-cholesterol concentrations in plasma of less than 10 mg/dl (men) respectively 15 mg/dl (women) participated in the study. The volunteers received 3 times 1 tablet daily over a period of 6 weeks equivalent to a daily dosage of 900 mg garlic powder in the active treated group. Control measurements were made on the 1st, 22nd and 43rd day of treatment and 0, 3 and 5 h after intake of the meal. The postprandial increase of triglycerides was clearly reduced under garlic medication as compared to placebo treatment. The determined AUC-values for the triglycerides were up to 35% lower in the garlic group compared to the placebo group. The regular intake of the garlic preparation over the period of 6 weeks showed a significant lowering of the fasting values of triglycerides in comparison to placebo. Under garlic medication HDL2-cholesterol increased more than under placebo in tendency. |
| Postprandial reduction in high-density lipoprotein cholesterol concentrations in postmenopausal women: improvement by 17beta-estradiol Westerveld, H. T., E. Meijer, et al. (1996), Metabolism 45(7): 827-32. Abstract: The aim of the study was to characterize postprandial high-density lipoprotein (HDL) cholesterol metabolism in postmenopausal women and to evaluate the effect of replacement therapy with 17beta-estradiol. Sixteen healthy normolipidemic (plasma cholesterol, 5.39 +/- 0.68 mmol/L; plasma triglycerides TGds, 1.24 +/- 0.55 mmol/L) postmenopausal women received an oral vitamin A fat tolerance test (50 g fat with 60,000 IU vitamin A/m2 body surface area). Various blood samples were taken before the test, at hourly intervals up to 8 hours, and 24 hours after ingestion of the fat load for determination of HDL cholesterol, HDL TG, and HDL apolipoprotein (apo) A-I concentrations. TG and vitamin A concentrations were also measured. A subgroup of six women were treated with 2 mg micronized 17beta-estradiol orally each day for 6 weeks, after which the oral vitamin A fat tolerance test was repeated. A reduction in plasma HDL cholesterol concentrations was observed 3 to 8 hours after ingestion of the fat load, and the minimal postprandial HDL cholesterol concentration was, on average, 31.7% (P =.04) lower than the fasting HDL cholesterol concentration. HDL cholesterol had returned to the initial value 24 hours after the fat load. The decrease in postprandial HDL cholesterol concentrations was attenuated by treatment with 17beta-estradiol. The area under the curve (AUC) for the postprandial reduction in HDL cholesterol improved substantially by 66% during 17beta-estradiol (-2.4 +/- 2.6 mmol x h x L(-1) before 17beta-estradiol and - 1.1 +/- 1.2 mmol x h x L(-1)_ during 17beta-estradiol, P =.038). In conclusion, HDL cholesterol concentrations decreased by 32% in the postprandial state in normolipidemic postmenopausal women, indicating that HDL cholesterol must be measured in the fasting state. Replacement therapy with 17beta-estradiol reduced the postprandial decrease in HDL cholesterol by 66%. This effect of 17beta-estradiol can be beneficial in reducing the risk of coronary artery disease. |
| Postprandial reverse cholesterol transport in type 2 diabetic patients: effect of a lipid lowering treatment Autran, D., N. Attia, et al. (2000), Atherosclerosis 153(2): 453-60. Abstract: Deterioration of reverse cholesterol transport (RCT), an important anti-atherogenic process, may contribute to the largely unexplained severity of cardiovascular risk in type 2 diabetic patients. Among other relevant metabolic perturbations is the impairment in type 2 patients of the postprandial increase in RCT which, in normal subjects, is associated with the transfer to HDL of PL from lipolyzed chylomicrons. We have explored the possibility that improvement of postprandial lipolysis by bezafibrate might also restore the stimulated level of postprandial RCT. Twelve male patients (HbA1c 7.6 +/- 1.6% triglycerides (TG) 4.5 +/- 2.4 mmol/l) were treated for 4 weeks with 400 mg bezafibrate and compared with seven age-matched controls. Lipoproteins were analyzed over 8 h after a 1000 Kcal fat load (80% lipid), serum mediated cholesterol efflux was evaluated using 3H-cholesterol labelled Fu5AH cells. Fasting efflux was lower in patients (17.9 +/- 3.3 vs 19.9 +/- 3.0 a. units, P < 0.05) and decreased postprandially in most instead of increasing, so that area under the time-curve (AUC) was 23% lower than in controls (140 +/- 23 vs 170 +/- 25 units x h, P < 0.001) The patients' HDL failed to acquire PL and gained TG in proportion to lipemia (r = 0.660, P < 0.001). Bezafibrate restored fasting efflux (19.6 +/- 3.6 units, P < 0.005 vs pretreatment) but not postprandial increase of efflux or HDL-PL. AUC of efflux was however improved to 155 +/- 23 units h (P < 0.02). Postprandial efflux related mainly to HDL-PL in controls and patients before treatment. HDL-TG emerged as a significant negative correlate common to all groups (r = -0.674, P < 0.001 8 h after the meal). Impairment of reverse cholesterol transport in diabetic patients might therefore be due to combined postprandial deficit of PL transfer and excess accumulation of TG in HDL. The significant improvement due to fibrate treatment might thus be related to the reduction of HDL-TG contents associated with the improvement of postprandial hyperlipemia. |
| Postprandial studies on dietary cholesterol in human subjects using stable isotopes and gas chromatography-mass spectrometry analysis Beaumier-Gallon, G., C. Dubois, et al. (1998), Atherosclerosis 141 Suppl 1: S81-5. Abstract: We hypothesized that intestinal absorption and postprandial re-secretion of dietary cholesterol may be a particularly complex process in humans. To test this hypothesis, we used deuterium-enriched cholesterol to specifically label meal cholesterol and developed an improved method for quantitative measurement of traces of deuterated cholesterol as well as cholesterol with reference to two different internal standards by gas chromatography-mass spectrometry (GC-MS) measurement. In the first study, a group of healthy subjects ingested a single test meal containing deuterated cholesterol with a 7 h postprandial follow-up. In the second one, a group of healthy subjects ingested a first test meal containing deuterated cholesterol and a follow-up was performed during three consecutive test meals and later until 72 h. The most striking observations were that the occurrence of dietary cholesterol in chylomicrons is not concomitant to triglycerides and is very low after a single meal while most dietary cholesterol is re-secreted in chylomicrons after a second, and even a third, fat test meal. The data obtained show that the re-secretion of dietary cholesterol from the small intestine is a slow and complex process in humans. |
| Postprandial variations in the cholesteryl ester transfer protein activity, phospholipid transfer protein activity and plasma cholesterol efflux capacity in normolipidemic men Syeda, F., C. Senault, et al. (2003), Nutr Metab Cardiovasc Dis 13(1): 28-36. Abstract: BACKGROUND AND AIM: Plasma cholesterol efflux capacity is stimulated during postprandial (PP) hypertriglycerdemia. Plasma cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are the key proteins in lipoprotein metabolism and remodelling, but their role during the PP cholesterol efflux process remains indeterminate. The aim of this study was to determine the effect of a fatty meal intake on plasma CETP and PLTP activities, and the capacity of plasma to promote cholesterol efflux, as well as to evaluate the relationship between these three key mechanisms of the reverse cholesterol transport process. METHODS AND RESULTS: CETP and PLTP activities and the cholesterol efflux capacity of plasma were measured over eight hours following a fatty meal (1000 kcal, 62% fat) in 13 normolipidemic men. CETP activity and the cholesterol efflux capacity of plasma from Fu5AH cells increased after the meal, reaching a maximum after eight hours (respectively 32%, p = 0.06, and 6.5%, p = 0.045), whereas PLTP activity remained unchanged. CETP and PLTP activities did not correlate with plasma cholesterol efflux capacity in the fasting or PP state. Plasma CETP activity in the fasting state positively correlated with the plasma non-esterified fatty acid (NEFA) levels, but no correlation was found with any lipid or apolipoprotein postprandially. The cholesterol efflux capacity of plasma correlated positively with high-density lipoprotein (HDL) components, the best correlation being with the HDL phospholipid fraction in both the fasting and PP states. CONCLUSIONS: These findings suggest that plasma CETP and PLTP activities in healthy normolipidemic subjects are differently regulated in the PP state, and are not correlated with the increased cholesterol efflux capacity of PP plasma. HDL-phospholipid remains the key factor in the regulation of the capacity of plasma to promote Fu5AH cell cholesterol efflux. |
| Postprandial vitamin A and squalene clearances and cholesterol synthesis off and on lovastatin treatment in type III hyperlipoproteinemia Gylling, H., H. Relas, et al. (1995), Atherosclerosis 115(1): 17-26. Abstract: Postprandial fat clearance and absorption, fecal elimination and synthesis of cholesterol, bile acid synthesis, and cholesterol precursors and plant sterols in serum were studied in five patients with type III dyslipoproteinemia off and on lovastatin. The basal values were related to those in nontreated normolipidemic control subjects with apolipoprotein E3/3 phenotype (apo E3 controls, n = 16). On regular home diets, cholesterol precursor concentrations and cholesterol precursor/cholesterol ratios were high in the type III group. However, cholesterol absorption efficiency, bile acid and cholesterol synthesis measured with sterol balance technique and the precursor sterol/plant sterol ratios in serum were similar to the control values, suggesting that cholesterol absorption and metabolism was normal in these subjects. Lovastatin normalized the increased lipoprotein concentrations and reduced biliary cholesterol secretion, absolute absorption of cholesterol, precursor sterol/cholesterol and precursor sterol/plant sterol ratios in serum, fecal neutral and total sterol outputs and cholesterol synthesis. Lovastatin had no effect on cholesterol absorption efficiency or bile acid synthesis. Despite normalization of the triglyceride-rich lipoprotein levels by lovastatin, the postprandial vitamin A and squalene peak concentrations and the areas under the curves remained above the control ranges. The findings show that in type III hyperlipidemia, the precursor sterol/cholesterol ratios do not predict cholesterol synthesis. The latter, bile acid synthesis, precursor sterol/plant sterol ratios in serum, and cholesterol absorption are normal under basal conditions. The normalization of increased lipids by lovastatin is mainly due to reduced synthesis and absolute absorption of cholesterol, while the retarded postprandial fat clearance was not normalized by the drug. |
| Post-transcriptional regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol 7 alpha-hydroxylase in rats with subtotal nephrectomy Pandak, W. M., Z. R. Vlahcevic, et al. (1994), Kidney Int 46(2): 358-64. Abstract: Chronic renal failure is associated with hyperlipidemia and atherosclerosis. The mechanism responsible for the observed increase of serum cholesterol in chronic renal disease is not certain. The objective of the present study was to characterize the effect of induced renal failure on 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) and cholesterol 7 alpha-hydroxylase, the two rate determining enzymes of the cholesterol and bile acid biosynthetic pathways, respectively. Studies were carried out in rats with subtotal (75%) nephrectomy, which resulted in a marked elevation of blood urea nitrogen (371 +/- 44% of control, P < 0.001), and was accompanied by significant increases in the levels of serum cholesterol (133 +/- 7%, P < 0.005) and triglycerides (185 +/- 25, P < 0.01). In nephrectomized rats, an increase in the specific activity of HMG-CoA reductase (219 +/- 30% above control levels, P < 0.02) was observed. This increase occurred in the presence of elevated hepatic microsomal cholesterol concentrations (150 +/- 13% of controls, P < 0.01). Surprisingly, the increase in HMG-CoA reductase specific activity was not associated with parallel increases in HMG-CoA reductase steady-state mRNA levels and gene transcriptional activity. These uremic rats also exhibited a marked increase in the specific activity of cholesterol 7 alpha-hydroxylase (240 +/- 559% of controls, P < 0.05). There was no concomitant increase in cholesterol 7 alpha-hydroxylase steady-state mRNA levels or gene transcriptional activity. The factors responsible for the observed increases in HMG-CoA reductase and cholesterol 7 alpha-hydroxylase specific activity in renal failure remain to be determined.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Post-transcriptional regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase by 3 beta-hydroxy-lanost-8-en-32-al, an intermediate in the conversion of lanosterol to cholesterol Leonard, D. A., M. A. Kotarski, et al. (1994), Arch Biochem Biophys 310(1): 152-7. Abstract: The lanosterol demethylation intermediate 3 beta-hydroxylanost-8-en-32-al is a known suppressor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), the rate-limiting enzyme of cholesterol biosynthesis. Studies on the mechanism of action of this compound have been hampered by its rapid metabolism. As one approach to this problem, the effects of 3 beta-hydroxy-lanost-8-en-32-al on HMGR gene expression were examined using a mutant cell line which lacks lanosterol 14 alpha-methyl demethylase activity. Data are presented which suggest that 3 beta-hydroxy-lanost-8-en-32-al inhibits HMGR gene expression by reducing the translational efficiency of the HMGR mRNA. We have recently reported that 15 alpha-fluoro-3 beta-hydroxy-lanost-7-en-32-aldehyde, a compound which is structurally similar to 3 beta-hydroxy-lanost-8-en-32-aldehyde, suppresses HMGR activity in cultured Chinese hamster ovary cells by a posttranscriptional process, inhibiting translation without affecting either transcription or enzyme degradation (Trzaskos et al., 1993, J. Biol. Chem. 268, 22591-22599). In contrast to the results obtained with the 15 alpha-fluorolanostenol, the lanostenol 32-aldehyde increased the rate of degradation of HMGR in a manner similar to that reported for oxycholesterols. These data suggest that 15 alpha-fluoro-3 beta-hydroxy-lanost-7-en-32-aldehyde and 3 beta-hydroxy-lanost-8-en-32-aldehyde, although structurally similar posttranscriptional regulators of HMGR suppress enzyme activity, at least in part, by different mechanisms. |