| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Macrophages mediate adverse effects of cholesterol feeding in experimental nephrosis Pesek-Diamond, I., G. Ding, et al. (1992), Am J Physiol 263(5 Pt 2): F776-83. Abstract: We tested whether the deleterious effects of hypercholesterolemia, in a progressive glomerular disease model, may be mediated by infiltrating renal macrophages. A single sublethal dose of whole body X-irradiation (XI) delivered to rats with acute puromycin aminonucleoside (PA) nephrosis fed a high-cholesterol (HC) diet resulted in significantly greater inulin and p-aminohippurate (PAH) clearances at 11 days after PA without any alterations in circulating lipid levels, in contrast to nonirradiated HC-fed nephrotic controls. This functional protection was associated with significant declines in both glomerular and cortical interstitial macrophage number. Over the course of this 16-wk model, HC-fed PA rats had significantly less albuminuria as well as significantly fewer glomerulosclerosis (GS) lesions and less mesangial matrix expansion at the end of the study despite an equivalent degree of sustained hypercholesterolemia. This data suggests that reducing the infiltrating glomerular and cortical interstitial macrophage burden with XI during acute PA nephrosis, unaccompanied by any hypolipidemic effect, produces not only early salutary effects on renal function but also a significant amelioration of the progressive glomerulopathic features of this model. This is consistent with the hypothesis that the infiltrating renal macrophage, in large part, directly mediates the adverse effects of hypercholesterolemia in this model. |
| Macrophages transfer cholesterol to lymphocytes in culture de Bittencourt, P. I., Jr. and R. Curi (1997), Biochem Soc Trans 25(2): 345S. |
| Macroscopic distribution of coronary atherosclerotic lesions in cholesterol-fed rabbits Kitajima, S., S. Sakuma, et al. (1998), Exp Anim 47(4): 221-7. Abstract: In the present study we macroscopically examined a change in the distribution of coronary atherosclerosis in cholesterol-fed rabbits. Rabbits were fed a cholesterol-enriched diet for 15 weeks, then replaced by a normal diet, and were sacrificed at 15, 24, 32 and 42 weeks after the start of the experiment. The coronary atherosclerosis in the cholesterol-fed rabbits was distributed more densely in the proximal portion than in the middle and distal portions, and the lesions were severe at 24 and 32 weeks after the start of the experiment. comparison of lesions in the three portions at these time points showed that the percentages of lesion areas in the proximal portion, the middle portion and the distal portion were approximately 51%, 21 to 25% and 0.2 to 3.7%, respectively. Macroscopic observation of the coronary atherosclerotic lesions showed that the lesions formed over the vessel lumen in the proximal portion within the range of approximately 5 mm from the orifice of the left coronary artery. In the middle portion, the lesions formed predominantly around the orifices of branches as small patchy lesions from 1 to 3 mm in diameter. These findings support previous histopathological reports that suggested that the incidence of stenosis in the proximal portion was high, and the incidence of lesion occurrence in the middle and the distal portions varied. The method, macroscopical investigation of the coronary artery, is useful for analyzing coronary atherosclerosis in the rabbit. |
| Magnesium status, serum HDL cholesterol, and apolipoprotein A-1 levels Nozue, T., A. Kobayashi, et al. (1995), J Pediatr Gastroenterol Nutr 20(3): 316-8. Abstract: To determine the relationship between low magnesium status and lipids, we divided 27 patients with microscopic hematuria and normal renal function into two groups according to magnesium retention, as measured by a magnesium-loading test, and compared their serum lipid and apolipoproteins. Patients with low magnesium status (n = 7) had significantly lower levels of cholesterol, HDL cholesterol, and apolipoprotein A-1 than those with normal magnesium status (n = 20); however, there were no significant differences between the groups in serum concentrations of magnesium and apolipoprotein B. These data suggest that magnesium deficiencies are associated with low serum concentration of HDL cholesterol and apolipoprotein A-1. |
| Magnetic resonance imaging for the visualization of cholesterol gallstones in hamster fed a new high sucrose lithogenic diet Cohen-Solal, C., M. Parquet, et al. (1995), J Hepatol 22(4): 486-94. Abstract: Cholesterol gallstone induction in hamster gallbladder is usually achieved by specific diets. An X-ray in vivo follow-up of cholelithiasis development in this species is impossible, since cholesterol gallstones are transparent as long as they are not calcified. Moreover, their size (0.2 to 1 mm) also prevents their detection by ultrasonography. The current study presents an in vivo cholesterol gallstone detection by magnetic resonance imaging in hamsters fed a new high sucrose diet containing a low proportion of cholesterol (0.015%) and a normal ratio of lipids (10%). The diet produced gallstones and an increase in the cholesterol saturation index in about 50% of animals after a 5-week feeding period. The visualization of gallstones by magnetic resonance imaging in anaesthetized animals required synchronization between breathing movements and image acquisition. A high magnetic field was also necessary to allow a fine image resolution, adapted to gallstone size. Two major advantages of this technique are a direct selection of lithiasic animals with a functional gallbladder (in spite of the presence of gallstones) and a possible adjustment of the treatment period of potential litholytic drugs. |
| Magnitude of dietary effects on plasma cholesterol concentration: role of sex and apolipoprotein E phenotype Savolainen, M. J., M. Rantala, et al. (1991), Atherosclerosis 86(2-3): 145-52. Abstract: The effects of fat-controlled, low-cholesterol and high-fat, high-cholesterol diets pursued for 4 weeks on plasma lipids and lipoproteins were studied in 44 healthy middle-aged subjects (22 women and 22 men). All the calories were supplied from the hospital kitchen. When the subjects were switched from the fat-controlled, low-cholesterol diet to the high-fat, high-cholesterol diet the average increase in total cholesterol was 1.2 mmol/l (28%), ranging from 0.2 to 2.7 mmol/l (4-56%). At the same time the average increase in LDL cholesterol was 1.0 mmol/l (39%), ranging from 0.1 to 2.4 mmol/l (3-90%). Interestingly, the men responded to the dietary changes more sensitively than the women. The increase in total cholesterol from the low-fat to the high-fat diet was 31% for the men and 25% for the women (P less than 0.05), the corresponding increases in LDL cholesterol being 42% and 37%, respectively (P less than 0.05). A marked increase in HDL cholesterol was observed when the subjects were switched from the low-fat to the high-fat diet, the increase being 30% for the men and 20% for the women. The absolute and percentage lipid changes on the two diets were equal in the subjects with the common apolipoprotein E phenotype 3/3 and in those homozygous and heterozygous for the epsilon 4 allele (E4/4 and E4/3).(ABSTRACT TRUNCATED AT 250 WORDS) |
| Magnitude of HDL cholesterol variation after high-dose atorvastatin is genetically determined at the LDL receptor locus in patients with homozygous familial hypercholesterolemia Sposito, A. C., S. Gonbert, et al. (2003), Arterioscler Thromb Vasc Biol 23(11): 2078-82. Abstract: OBJECTIVE: The combination of LDL apheresis with high doses of a potent hepatic hydroxymethylglutaryl coenzyme A reductase inhibitor, such as atorvastatin, has been the best therapy available for the prevention of cardiovascular disease in patients with homozygous familial hypercholesterolemia (HFH). However, some concerns have been made about the effect of atorvastatin on HDL cholesterol levels in these patients. METHODS AND RESULTS: HDL cholesterol levels were determined bimonthly over the course of 2 years of treatment with high-dose atorvastatin in genotypically defined HFH patients either receptor-defective (n=6) or receptor-negative (n=6) under long-term treatment with LDL apheresis. We additionally stratified the atorvastatin effect on HDL cholesterol according to the genotype as an indicator of residual in vivo LDL receptor activity. Our findings indicate that (1) an early and transitory reduction of plasma HDL cholesterol levels occurs during the first 4 weeks of atorvastatin treatment; (2) the degree of the transient HDL reduction is higher in receptor-negative than in receptor-defective patients (-21+/-11 versus -10+/-4%; P=0.01); and (3) after long-term treatment, HDL cholesterol concentration remains higher in receptor-defective than receptor-negative patients (P=0.026). CONCLUSIONS: The present study reveals that HDL cholesterol reduction after high-dose atorvastatin is an early and transient event in HFH patients which magnitude depends on the presence of a residual LDL-R activity. |
| Magnolol attenuates VCAM-1 expression in vitro in TNF-alpha-treated human aortic endothelial cells and in vivo in the aorta of cholesterol-fed rabbits Chen, Y. H., S. J. Lin, et al. (2002), Br J Pharmacol 135(1): 37-47. Abstract: 1. In a previous study, we showed that magnolol, a potent antioxidant derived from a Chinese herb, attenuates monocyte chemotactic protein-1 (MCP-1) expression and intimal hyperplasia in the balloon-injured aorta of cholesterol-fed rabbits. Expression of cell adhesion molecules by the arterial endothelium and the attachment of leukocytes to the endothelium may play a major role in atherosclerosis. In the present study, the effects of magnolol on the expression of endothelial-leukocyte adhesion molecules and the activation of nuclear factor kappa B (NF-kappa B) in tumour necrosis factor-alpha (TNF-alpha)-treated human aortic endothelial cells (HAECs) were investigated. 2. Pretreatment of HAECs with magnolol (5 microM) significantly suppressed the TNF-alpha-induced expression of vascular cell adhesion molecule-1 (VCAM-1) (64.8+/-1.9%), but had no effect on the expression of intercellular cell adhesion molecule-1 and endothelial cell selectin. 3. Magnolol (5 and 10 microM) significantly reduced the binding of the human monocytic cell line, U937, to TNF-alpha-stimulated HAECs (58.4 and 56.4% inhibition, respectively). Gel shift assays using the (32)P-labelled NF-kappa B consensus sequence as probe showed that magnolol pretreatment reduced the density of the shifted bands seen after TNF-alpha-induced activation. Immunoblot analysis and immunofluorescence staining of nuclear extracts demonstrated a 58% reduction in the amount of NF-kappa B p65 in the nuclei in magnolol-treated HAECs. Magnolol also attenuated intracellular H(2)O(2) generation in both control and TNF-alpha treated HAECs. 4. Furthermore, in vivo, magnolol attenuates the intimal thickening and TNF-alpha and VCAM-1 protein expression seen in the thoracic aortas of cholesterol-fed rabbits. 5. Taken together, these data demonstrate that magnolol inhibits TNF-alpha-induced nuclear translocation of NF-kappa B p65 and thereby suppresses expression of VCAM-1, resulting in reduced adhesion of leukocytes. These results suggest that magnolol has anti-inflammatory properties and may play important roles in the prevention of atherosclerosis and inflammatory responses in vivo. |
| Magnolol, a potent antioxidant from Magnolia officinalis, attenuates intimal thickening and MCP-1 expression after balloon injury of the aorta in cholesterol-fed rabbits Chen, Y. L., K. F. Lin, et al. (2001), Basic Res Cardiol 96(4): 353-63. Abstract: BACKGROUND: Restenosis is a common complication after balloon angioplasty. A number of cytokines, chemotactic factors and growth factors may be involved. Several antioxidants have been shown to inhibit intimal thickening after balloon injury in hyperlipidemic animals. OBJECTIVES: The effects of magnolol on the expression of monocyte chemotactic protein-1 (MCP-1) and intimal response in balloon injured aorta of cholesterol-fed rabbits were investigated. METHODS: Male New Zealand white rabbits were fed a 2% high cholesterol (HC) diet together with daily intramuscular injection of either 1 microg/kg B.W. of magnolol (HC-M, n = 10) or vehicle (propylene glycol) as a control (HC-C, n = 10) for a total of 6 weeks. Another 10 rabbits fed a regular diet also served as a control (C) group. A balloon denudation of abdominal aorta was performed in each group at the end of the third week. The aortas were harvested at the end of 6 weeks. RESULTS: Magnolol treatment significantly inhibited Cu2+-induced LDL oxidation in cholesterol-fed rabbits and reduced atheroma formation atheroma area ratio: 0.10 +/- 0.03 (HC-M) versus 0.33 +/- 0.07 (HC-C), p < 0.05 in thoracic aortas without lowering serum cholesterol. The intimal response was significantly attenuated in the HC-M rabbits when compared to those of the HC-C group intimal thickness: 88.95 +/- 14.91 microm (HC-M) versus 198.02 +/- 20.35 microm (HC-C), p < 0.05; intimal area: 278.21 +/- 43.16 x 10(3) microm2 (HC-M) versus 642.70 +/- 65.01 x 10(3) microm2 (HC-C), p < 0.05. The MCP-1 mRNA and protein expression were reduced in the HC-M group compared to the HC-C and C groups. CONCLUSION: The inhibitory effects on intimal hyperplasia and MCP-1 expression might be attributed to the antioxidant capacity of magnolol instead of lowering serum cholesterol. Magnolol may offer some protection against postangioplasty restenosis. |
| Main risk factors for nephropathy in type 2 diabetes mellitus are plasma cholesterol levels, mean blood pressure, and hyperglycemia Ravid, M., D. Brosh, et al. (1998), Arch Intern Med 158(9): 998-1004. Abstract: BACKGROUND: The control of hyperglycemia is of major importance in the treatment of patients with type 1 diabetes mellitus. However, there is no consensus about the required degree of metabolic control in patients with type 2 diabetes mellitus and about the role of hyperglycemia in diabetic nephropathy and in the development of atherosclerosis in relation to other risk factors. PATIENTS AND METHODS: A prospective, long-term follow-up study was conducted on 574 patients, aged 40 to 60 years, with recent onset of type 2 diabetes mellitus. Patients were initially normotensive and had normal renal function and a normal urinary albumin excretion rate (<30 mg/24 h). The patients were followed up for 2 to 9 years (mean +/- SD, 7.8 +/- 0.9 years). Levels of hemoglobin A1c and plasma lipids, mean blood pressure, and body mass index (calculated as the weight in kilograms divided by the square of the height in meters) were determined periodically. Cigarette smoking and socioeconomic status were recorded. Renal status was evaluated by the logarithm of the final urinary albumin excretion rate and by the decline in reciprocal creatinine values. Definite clinical events including death, nonfatal myocardial infarction, angina pectoris, congestive heart failure, and peripheral vascular disease were recorded. RESULTS: At the end of the study the urinary albumin excretion rate remained normal (<30 mg/24 h) in 373 patients (65%), 111 (19%) had microalbuminuria (30-300 mg/24 h), and 90 (16%) had overt albuminuria (>300 mg/24 h). Logistic regression models demonstrated that the correlation between hemoglobin A1c levels and the risk of albuminuria is exponential. Multiple logistic regression analysis indicated that levels of total cholesterol, mean blood pressure, and hemoglobin A1c were the main factors associated with the decrease in renal function and with the increase in albuminuria. The combination of values higher than the 50th percentile of all 3 factors defined a high-risk patient population. These high-risk patients had an odds ratio of 43 (95% confidence interval, 25-106) for microalbuminuria and 15 (95% confidence interval, 9-25) for clinical events related to arteriosclerosis compared with the rest of the group. Low levels of high-density lipoprotein, body mass index, cigarette smoking, low socioeconomic status, and male sex were all significantly associated with diabetic nephropathy, as well as with the manifestations of arteriosclerosis. CONCLUSIONS: The combination of blood pressure values in the high-normal range with moderately elevated levels of total cholesterol and hemoglobin A1c defines a high-risk group for the progression to diabetic nephropathy and for clinical events related to arteriosclerotic cardiovascular disease. |
| Maintaining cholesterol homeostasis: sterol regulatory element-binding proteins Weber, L. W., M. Boll, et al. (2004), World J Gastroenterol 10(21): 3081-7. Abstract: The molecular mechanism of how hepatocytes maintain cholesterol homeostasis has become much more transparent with the discovery of sterol regulatory element binding proteins (SREBPs) in recent years. These membrane proteins are members of the basic helix-loop-helix-leucine zipper (bHLH-Zip) family of transcription factors. They activate the expression of at least 30 genes involved in the synthesis of cholesterol and lipids. SREBPs are synthesized as precursor proteins in the endoplasmic reticulum (ER), where they form a complex with another protein, SREBP cleavage activating protein (SCAP). The SCAP molecule contains a sterol sensory domain. In the presence of high cellular sterol concentrations SCAP confines SREBP to the ER. With low cellular concentrations, SCAP escorts SREBP to activation in the Golgi. There, SREBP undergoes two proteolytic cleavage steps to release the mature, biologically active transcription factor, nuclear SREBP (nSREBP). nSREBP translocates to the nucleus and binds to sterol response elements (SRE) in the promoter/enhancer regions of target genes. Additional transcription factors are required to activate transcription of these genes. Three different SREBPs are known, SREBPs-1a, -1c and -2. SREBP-1a and -1c are isoforms produced from a single gene by alternate splicing. SREBP-2 is encoded by a different gene and does not display any isoforms. It appears that SREBPs alone, in the sequence described above, can exert complete control over cholesterol synthesis, whereas many additional factors (hormones, cytokines, etc.) are required for complete control of lipid metabolism. Medicinal manipulation of the SREBP/SCAP system is expected to prove highly beneficial in the management of cholesterol-related disease. |
| Maintenance of cholesterol reduction using automated telephone calls Hyman, D. J., J. A. Herd, et al. (1996), Am J Prev Med 12(2): 129-33. Abstract: A critical problem in the dietary treatment of hypercholesterolemia is the long-term maintenance of cholesterol reduction. A system to maintain contact and provide feedback through a computer-interactive phone system was used with 115 subjects who completed a four-week diet and behavioral cholesterol reduction program. The subjects, mean age 48 years, were 87% non-Hispanic Caucasian and 74.8% were female. They were randomized to a control or maintenance group. The maintenance group received calls twice a month for six months. Total cholesterol (TC) and weight (lb) were obtained before and after a four-week program and after the six-month maintenance period. Neither group of subjects with all cholesterol measurements fully maintained initial cholesterol reductions (mean TC: in maintenance n = 48) 248, 221, 231 versus control n = 43 243, 224, 232 mg/dL). All (n = 59) of the maintenance subjects used the phone system, with 83.3% of a subset evaluating it indicating the phone messages were helpful. Patients (n = 25) with > or = 5 lb weight loss and 10% TC decrease from baseline had a better maintenance of TC reduction in the maintenance versus control group (273,208,231 versus 259,205,246 mg/dL) (P <.05). We conclude that (1) maintenance remains a problem for cholesterol-lowering diet interventions, (2)automated phone calls are capable of maintaining contact and providing patient feedback, and (3) this system may help in the maintenance of TC levels for patients who made greater changes. |
| Major proteins of bovine seminal plasma and high-density lipoprotein induce cholesterol efflux from epididymal sperm Therien, I., R. Moreau, et al. (1998), Biol Reprod 59(4): 768-76. Abstract: One of the hypotheses to explain the mechanism of capacitation involves the loss of sperm membrane cholesterol. Here, we studied whether or not the major proteins of bovine seminal plasma designated as BSP-A1, -A2, -A3, and -30-kDa (collectively called BSP proteins), which are implicated in sperm capacitation, induce cholesterol efflux. When epididymal sperm were labeled with 3Hcholesterol and incubated with bovine seminal plasma (0.05-2%) or BSP proteins (20-120 microg/ml) for 8 h, the sperm lost 3Hcholesterol (3.6-fold and 3-fold, respectively). The same results in the presence of BSP-A1/-A2 were obtained (3.5-fold) by direct determination of cholesterol on unlabeled epididymal sperm. Analysis of efflux particles by ultracentrifugation on a sucrose gradient revealed a single symmetrical peak of radioactivity at 1.14 g/ml. Immunoblotting of the fractions obtained from size-exclusion chromatography of the efflux particles showed that a portion of the BSP proteins were associated with 3Hcholesterol. Heparin (12 microg/ml) alone did not stimulate cholesterol efflux. In contrast, high-density lipoprotein (HDL, 100 microg/ml) alone stimulated cholesterol efflux up to 3.1-fold after 8 h. When labeled epididymal sperm were preincubated for 20 min with BSP-A1/-A2 (120 microg/ml), washed, and incubated with HDL (100 microg/ml) for 8 h, the total cholesterol efflux of the sperm suspension was 51.8 +/- 5.0% compared to 39.3 +/- 1.2% when HDL alone was used. These results indicate that BSP proteins and HDL play an important role in the sperm sterol efflux that occurs during capacitation. Furthermore, the heparin-induced sperm capacitation did not involve the efflux of sperm membrane cholesterol. |
| Make low-cholesterol diets tasty La Puma, J. (1994), Ann Intern Med 120(7): 621-2. |
| Making the most of cholesterol-lowering margarines Avery, J. K. (2001), Cleve Clin J Med 68(3): 194-6. Abstract: Used as a substitute for normal dietary intake of saturated fatty acids, margarines containing plant sterols can cause a modest reduction in serum total cholesterol and low-density lipoprotein cholesterol levels. They have been shown effective in patients with mild hypercholesterolemia, but they are also useful in the general population. |
| Male gender increases sensitivity to renal injury in response to cholesterol loading Attia, D. M., R. Goldschmeding, et al. (2003), Am J Physiol Renal Physiol 284(4): F718-26. Abstract: Males are at greater risk for renal injury than females. This may relate to nitric oxide (NO) availability, because female rats have higher renal endothelial NO synthase (NOS) levels. Previously, our laboratory found susceptibility to proteinuria induced by NOS inhibition in male compared with female rats. Dyslipidemia and hypercholesterolemia dose dependently decreased renal NOS activity and caused renal injury in female rats. We hypothesized that exposure of male rats to hypercholesterolemia would lead to more renal injury in male than in female rats due to an a priori lower renal NO system. Female and male rats were fed no, low-dose, or high-dose cholesterol for 24 wk. Cholesterol feeding dose dependently increased proteinuria in both female and male rats, but male rats developed more proteinuria at similar plasma cholesterol (P < 0.001). Control males had lower renal NOS activity than control females (4.44 +/- 0.18 vs. 7.46 +/- 0.37 pmol. min(-1). mg protein(-1); P < 0.05), and cholesterol feeding decreased renal NOS activity in males and in females (P < 0.05). Cholesterol-fed males developed significantly more vascular, glomerular, and tubulointerstitial monocyte/macrophage influx and injury than females. Thus under baseline conditions, male rats have lower renal NOS activity than female rats. This may explain why male rats are more sensitive to renal injury by factors that decrease NO availability, such as hypercholesterolemia. |
| Malformation syndromes due to inborn errors of cholesterol synthesis Porter, F. D. (2002), J Clin Invest 110(6): 715-24. |
| Malondialdehyde modification and copper-induced autooxidation of high-density lipoprotein decrease cholesterol efflux from human cultured fibroblasts Salmon, S., C. Maziere, et al. (1992), Biochim Biophys Acta 1125(2): 230-5. Abstract: Malondialdehyde modification and copper ion-induced autooxidation of the apo E-free HDL3 fraction of high-density lipoproteins were studied with respect to physico-chemical characteristics and physiological properties of the lipoprotein. Cu(2+)-oxidized HDL was much less modified than MDA-treated HDL, in terms of electrophoretic mobility, lipid peroxidation product content, Lys and Trp amino acid residue level and polymerization of apo A-I. With 3Hcholesteryl linoleate-labeled LDL, an inhibition of cholesterol efflux was observed in the presence of modified HDL, with a more marked effect with MDA-modified HDL. Competition studies with iodinated native HDL demonstrated a decreased binding of modified HDL to cell surface receptors. The decrease in cholesterol intracellular content, determined either by the isotopic equilibrium method or by the enzymatic cholesterol oxidase technic, was less marked in the presence of modified HDL than in the presence of native HDL. MDA-modified HDL was the less effective in decreasing cellular cholesterol content. It is thus suggested that malondialdehyde-induced alteration of HDL, or HDL peroxidation, if occurring in vivo, could contribute to the progress of atherogenesis by decreasing cholesterol efflux from peripheral tissues. |
| Malondialdehyde-modified HDL leads to accumulation of cholesterol in rat liver endothelial cells Guertin, F., S. Brunet, et al. (1995), Biochem Biophys Res Commun 212(1): 1-8. Abstract: In order to study in vivo the effect of modified high density lipoprotein (HDL) on the movement of free cholesterol to liver cells and bile, we injected i.v. into rats, native or malondialdehyde modified HDL labelled with 14Ccholesterol. Bile analysis indicated that the contribution of labelled cholesterol to bile acid secretion was diminished in the group receiving MDA-modified HDL when compared to control group. On the other hand, the liver analysis revealed higher radioactivity in the treated group. A separation of liver cells into parenchymal, endothelial, and kupffer at 90 min after the injection of MDA-modified HDL or native HDL indicated that the endothelial cell uptake of labelled free cholesterol from MDA-modified HDL was 2.6-fold higher than for native HDL. It is suggested that liver endothelial cells may be involved in the protection against atherogenoic oxidized lipoprotein. However, with regard to our finding, the uptake of cholesterol from modified HDL was detrimental to bile acid secretion. |
| Malondialdehyde-modified high-density lipoprotein cholesterol: plasma removal, tissue distribution and biliary sterol secretion in rats Guertin, F., S. Brunet, et al. (1994), Biochim Biophys Acta 1214(2): 137-42. Abstract: Evidence has been accumulating for the putative role of chemically or oxidatively altered lipoproteins in accelerating events in the atherogenic process. In this study, the movement of free cholesterol from native high density lipoprotein (HDL) and malondialdehyde (MDA)-modified HDL to the liver for biliary cholesterol secretion and bile acid transformation was examined in vivo. To this end, HDL from normal donor rats was isolated, conjugated with MDA, labelled with 14Ccholesterol and injected i.v. into rats with bile diversion. While the 6 h collection revealed no substantial differences in bile flow, less 14C excretion was recovered in the fresh bile of animals receiving MDA-modified HDL. Bile analysis indicated that a significant decline in labelled bile acid secretion characterized these rats. Compared with controls, MDA-modified HDL also caused an enhanced accumulation of 14Ccholesterol in the liver and the kidneys, with reduced delivery to the sites of steroidogenesis, i.e., the adrenals and testes. No plasma removal differences were noted in the HDL of both groups of rats. Thus, modification of HDL by MDA seems to impair the tissue distribution of its cholesterol moiety, particularly in the liver, where it accumulates at the expense of bile acid transformation. |