| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
| First Page | Previous Page | Next Page | Last Page |
| Lipophilic 1,1-bisphosphonates are potent squalene synthase inhibitors and orally active cholesterol lowering agents in vivo Ciosek, C. P., Jr., D. R. Magnin, et al. (1993), J Biol Chem 268(33): 24832-7. Abstract: Squalene synthase catalyzes the reductive dimerization of two molecules of farnesyl diphosphate to form squalene at the final branchpoint of the cholesterol biosynthetic pathway. We report herein that isoprenyl 1,1-bisphosphonates and related analogs are potent inhibitors of rat microsomal squalene synthase (I50 = 0.7-32 nM). In addition, members of this family are potent inhibitors of cholesterol biosynthesis in rats on intravenous and oral dosing, as well as cholesterol lowering agents in rats and hamsters. Significant inhibition of cholesterol biosynthesis in rats by lovastatin occurs with a concomitant inhibition of dolichol and coenzyme-Q9 synthesis. In contrast, bisphosphonate 4 has no effect on dolichol and coenzyme-Q9 biosynthesis in rats under conditions where cholesterol biosynthesis is > 90% inhibited. |
| Lipoplex-mediated transfection of mammalian cells occurs through the cholesterol-dependent clathrin-mediated pathway of endocytosis Zuhorn, I. S., R. Kalicharan, et al. (2002), J Biol Chem 277(20): 18021-8. Abstract: Synthetic amphiphiles are widely used as a carrier system. However, to match transfection efficiencies as obtained for viral vectors, further insight is required into the properties of lipoplexes that dictate transfection efficiency, including the mechanism of delivery. Although endocytosis is often referred to as the pathway of lipoplex entry and transfection, its precise nature has been poorly defined. Here, we demonstrate that lipoplex-mediated transfection is inhibited by more than 80%, when plasma membrane cholesterol is depleted with methyl-beta-cyclodextrin. Cholesterol replenishment restores the transfection capacity. Investigation of the cellular distribution of lipoplexes after cholesterol depletion revealed an exclusive inhibition of internalization, whereas cell-association remained unaffected. These data strongly support the notion that complex internalization, rather than the direct translocation of plasmid across the plasma membrane, is a prerequisite for accomplishing effective lipoplex-mediated transfection. We demonstrate that internalized lipoplexes colocalize with transferrin in early endocytic compartments and that lipoplex internalization is inhibited in potassium-depleted cells and in cells overexpressing dominant negative Eps15 mutants. In conjunction with the notion that caveolae-mediated internalization can be excluded, we conclude that efficient lipoplex-mediated transfection requires complex internalization via the cholesterol-dependent clathrin-mediated pathway of endocytosis. |
| Lipopolysaccharides in bacterial membranes act like cholesterol in eukaryotic plasma membranes in providing protection against melittin-induced bilayer lysis Allende, D. and T. J. McIntosh (2003), Biochemistry 42(4): 1101-8. Abstract: Melittin is a small, cationic peptide that, like many other antimicrobial peptides, lyses cell membranes by acting on their lipid bilayers. However, the sensitivity to antimicrobial peptides varies among cell types. We have performed direct binding and vesicle leakage experiments to determine the sensitivity to melittin of bilayers composed of various physiologically relevant lipids, in particular, key components of eukaryotic membranes (cholesterol) and bacterial outer membranes (lipopolysaccharide or LPS). Melittin binds to bilayers composed of both zwitterionic and negatively charged phospholipids, as well as to the highly charged LPS bilayers. The magnitude of the free energy of binding (deltaG degrees) increases with increasing bilayer charge density; deltaG degrees = -7.6 kcal/mol for phosphatidylcholine (PC) bilayers and -8.9 to -11.0 kcal/mol for negatively charged bilayers containing phosphatidylserine (PS), phospholipids with covalently attached polyethylene glycol (PEG-lipids), or LPS. Comparisons of these data show that binding is not markedly affected by the steric barrier produced by the PEG in PEG-lipids or by the polysaccharide core of LPS. The addition of equimolar cholesterol to PC bilayers reduces the level of binding (deltaG degrees = -6.4 kcal/mol) and reduces the extent of melittin-induced leakage by 20-fold. LPS and 1:1 PC/cholesterol bilayers have similar high resistance to melittin-induced leakage, indicating that cholesterol in eukaryotic plasma membranes and LPS in Gram-negative bacteria provide strong protection against the lytic effects of melittin. We argue that this resistance is due at least in part to the similar tight packing of the lipid acyl chains in PC/cholesterol and LPS bilayers. The addition of bacterial phospholipids to LPS bilayers increases their sensitivity to melittin, helping to explain the higher sensitivity of deep rough bacteria compared to smooth phenotypes. |
| Lipoprotein (a) and cholesterol in body builders using anabolic androgenic steroids Cohen, L. I., C. G. Hartford, et al. (1996), Med Sci Sports Exerc 28(2): 176-9. Abstract: We examined the influence of self-administered anabolic androgenic steroids (AAS) on the lipogram of male body builders. Serum lipoprotein (a) (Lp(a)), total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured in 10 experimental and 8 control male competitive body builders. The proportion of subjects with serum Lp(a) levels above 30 mg.dl-1 was significantly lower in the AAS group than the non-AAS group. HDL-C levels were significantly lower and LDL-C levels significantly higher in the AAS group than the non-AAS group. These data suggest that AAS in male body builders have a beneficial effect on serum Lp(a) levels but reduce the HDL-C:LDL-C ratio. |
| Lipoprotein (a) and the evaluation of low density cholesterol by the Friedewald formula: a new problem for an old equation Hernandez, C., P. Chacon, et al. (1999), Med Clin (Barc) 113(8): 290-1. Abstract: BACKGROUND: To evaluate the influence of lipoprotein(a) Lp(a) concentration on the LDL-cholesterol calculated by the Friedewald formula. MATERIAL AND METHODS: Lp(a) was determined to a worker population of 947 subject in order to perform a correction of LDL-cholesterol obtained by the Friedewald formula. RESULTS: In subjects in whom Lp(a) was > 30 mg/dl (12.9%) LDL-cholesterol levels were overestimated 10 mg/dl at least. CONCLUSION: Lp(a) should be considered in order to reduce Friedewald's formula error on the estimation of LDL-cholesterol. |
| Lipoprotein (a), cholesterol and triglycerides in women with venous thromboembolism McColl, M. D., N. Sattar, et al. (2000), Blood Coagul Fibrinolysis 11(3): 225-9. Abstract: Plasma concentrations of lipoprotein (a), total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglyceride were measured in 62 women who had suffered an episode of objectively confirmed venous thromboembolism (VTE) at < or = 50 years of age, and in 98 age-matched female controls. The mean body mass index (BMI) of cases was significantly (P < 0.001) higher than that of controls. Plasma triglyceride was significantly higher, and total cholesterol/LDL- and HDL-cholesterol significantly lower, in cases compared with controls. After adjustment for BMI, the plasma total cholesterol and LDL-cholesterol remained significantly lower in cases. No significant differences in mean plasma lipoprotein (a) levels were identified between cases and controls. Lipoprotein (a) does not appear to be significantly associated with the development of VTE in young women. The increased risk of VTE in obese subjects may be mediated, at least in part, via hypertriglyceridaemia, which has previously been demonstrated to have effects on levels of coagulation factors, natural anticoagulants, and plasminogen activator inhibitor type 1. |
| Lipoprotein and cholesterol metabolism in diet-induced coronary artery atherosclerosis in primates. Role of cholesterol and fatty acids Rudel, L. L., J. S. Parks, et al. (1998), Prog Lipid Res 37(6): 353-70. |
| Lipoprotein cholesterol and atherosclerosis Kruth, H. S. (2001), Curr Mol Med 1(6): 633-53. Abstract: Progressive accumulation of cholesterol in the arterial wall causes atherosclerosis, the pathologic process underlying most heart attacks and strokes. Low density lipoprotein (LDL), the major carrier of blood cholesterol, has been implicated in the buildup of cholesterol in atherosclerotic plaques. Endothelial cells that line arteries function to transport LDL into the vessel wall. Models for the mechanism of cholesterol accumulation in atherosclerotic plaques emphasize increased LDL uptake into the vessel wall or increased retention of LDL that has entered the vessel wall. This article reviews the pathways of cholesterol entry and removal, the metabolism, and the physical changes of cholesterol in the vessel wall. How these processes are believed to contribute to cholesterol buildup in atherosclerotic plaques is discussed. |
| Lipoprotein cholesterol uptake mediates up-regulation of bile-acid synthesis by increasing cholesterol 7alpha-hydroxylase but not sterol 27-hydroxylase gene expression in cultured rat hepatocytes Post, S. M., J. Twisk, et al. (1999), Biochem J 341 (Pt 2): 339-46. Abstract: Lipoproteins may supply substrate for the formation of bile acids, and the amount of hepatic cholesterol can regulate bile-acid synthesis and increase cholesterol 7alpha-hydroxylase expression. However, the effect of lipoprotein cholesterol on sterol 27-hydroxylase expression and the role of different lipoproteins in regulating both enzymes are not well established. We studied the effect of different rabbit lipoproteins on cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase in cultured rat hepatocytes. beta-Migrating very-low-density lipoprotein (betaVLDL) and intermediate-density lipoprotein (IDL) caused a significant increase in the intracellular cholesteryl ester content of cells (2. 3- and 2-fold, respectively) at a concentration of 200 microgram of cholesterol/ml, whereas high-density lipoprotein (HDL, 50% v/v), containing no apolipoprotein E (apo E), showed no effect after a 24-h incubation. betaVLDL and IDL increased bile-acid synthesis (1. 9- and 1.6-fold, respectively) by up-regulation of cholesterol 7alpha-hydroxylase activity (1.7- and 1.5-fold, respectively). Dose- and time-dependent changes in cholesterol 7alpha-hydroxylase mRNA levels and gene expression underlie the increase in enzyme activity. Incubation of cells with HDL showed no effect. Sterol 27-hydroxylase gene expression was not affected by any of the lipoproteins added. Transient-expression experiments in hepatocytes, transfected with a promoter-reporter construct containing the proximal 348 nucleotides of the rat cholesterol 7alpha-hydroxylase promoter, showed an enhanced gene transcription (2-fold) with betaVLDL, indicating that a sequence important for a cholesterol-induced transcriptional response is located in this part of the cholesterol 7alpha-hydroxylase gene. The extent of stimulation of cholesterol 7alpha-hydroxylase is associated with the apo E content of the lipoprotein particle, which is important in the uptake of lipoprotein cholesterol. We conclude that physiological concentrations of cholesterol in apo E-containing lipoproteins increase bile-acid synthesis by stimulating cholesterol 7alpha-hydroxylase gene transcription, whereas HDL has no effect and sterol 27-hydroxylase is not affected. |
| Lipoprotein cholesterol, apolipoprotein A-I and B and lipoprotein (a) abnormalities in men with premature coronary artery disease Genest, J., Jr., J. R. McNamara, et al. (1992), J Am Coll Cardiol 19(4): 792-802. Abstract: The prevalence of abnormalities of lipoprotein cholesterol and apolipoproteins A-I and B and lipoprotein (a) Lp(a) was determined in 321 men (mean age 50 +/- 7 years) with angiographically documented coronary artery disease and compared with that in 901 control subjects from the Framingham Offspring Study (mean age 49 +/- 6 years) who were clinically free of coronary artery disease. After correction for sampling in hospital, beta-adrenergic medication use and effects of diet, patients had significantly higher cholesterol levels (224 +/- 53 vs. 214 +/- 36 mg/dl), triglycerides (189 +/- 95 vs. 141 +/- 104 mg/dl), low density lipoprotein (LDL) cholesterol (156 +/- 51 vs. 138 +/- 33 mg/dl), apolipoprotein B (131 +/- 37 vs. 108 +/- 33 mg/dl) and Lp(a) levels (19.9 +/- 19 vs. 14.9 +/- 17.5 mg/dl). They also had significantly lower high density lipoprotein (HDL) cholesterol (36 +/- 11 vs. 45 +/- 12 mg/dl) and apolipoprotein A-I levels (114 +/- 26 vs. 136 +/- 32 mg/dl) (all p less than 0.005). On the basis of Lipid Research Clinic 90th percentile values for triglycerides and LDL cholesterol and 10th percentile values for HDL cholesterol, the most frequent dyslipidemias were low HDL cholesterol alone (19.3% vs. 4.4%), elevated LDL cholesterol (12.1% vs. 9%), hypertriglyceridemia with low HDL cholesterol (9.7% vs. 4.2%), hypertriglyceridemia and elevated LDL cholesterol with low HDL cholesterol (3.4% vs. 0.2%) and Lp(a) excess (15.8% vs. 10%) in patients versus control subjects, respectively (p less than 0.05). Stepwise discriminant analysis indicates that smoking, hypertension, decreased apolipoprotein A-I, increased apolipoprotein B, increased Lp(a) and diabetes are all significant (p less than 0.05) factors in descending order of importance in distinguishing patients with coronary artery disease from normal control subjects. Not applying a correction for beta-adrenergic blocking agents, sampling bias and diet effects leads to a serious underestimation of the prevalence of LDL abnormalities and an overestimation of HDL abnormalities in patients with coronary artery disease. However, 35% of patients had a total cholesterol level less than 200 mg/dl after correction; of those patients, 73% had an HDL cholesterol level less than 35 mg/dl. |
| Lipoprotein composition and serum cholesterol ester fatty acids in nonwesternized Melanesians Lindeberg, S., P. Nilsson-Ehle, et al. (1996), Lipids 31(2): 153-8. Abstract: In this study, the relationships between dietary fat as measured by serum cholesterol ester fatty acids (CE-FA), age, smoking, body mass index, and serum lipids were analyzed in 151 subsistence horticulturalists, aged 20-86 yr, from Kitava, Trobriand Islands, Papua New Guinea. Their diet consists of tubers, fruit, coconut, fish, and vegetables with a negligible influence of western food and alcohol. Total fat intake is low 21% of energy (en%), while saturated fat intake from coconuts is high (17 en%, mainly lauric and myristic acid). In multivariate analysis, 11-43% of the variation of the serum lipoprotein composition was explained by CE-FA, age, and smoking habits. The proportion of CE20:5n-3 explained much of the variation of triglycerides (TG, negative relation) and high density lipoprotein-cholesterol (HDL-C, positive) in both sexes and serum apolipoprotein A1 (ApoA1, positive) in the males. CE16:0 was positively related to TG and negatively related to HDL-C and ApoA1 in both sexes, and in males it related negatively to total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C). In males, negative relationships were present between CE18:2n-6 and TC and between CE14:0 and serum lipoprotein(a). Smoking was independently associated with lower ApoA1 in both sexes and with lower HDL-C and higher TG, TC, LDL-C, and apolipoprotein B in males. In conclusion, marine n-3 fatty acids and linoleic acid showed the same potentially beneficial relationships with lipoproteins and apolipoproteins as in western populations. The relations of palmitic acid to serum lipids may be explained in terms of endogenous fat synthesis at a low-fat intake, rather than reflecting its relative intake. |
| Lipoprotein degradation and cholesterol esterification in primary cell cultures of rabbit atherosclerotic lesions Jaakkola, O. and T. Nikkari (1990), Am J Pathol 137(2): 457-65. Abstract: Lipoprotein metabolism and cholesterol accumulation in atherosclerotic lesions was studied using enzymatically isolated primary cell cultures from aortas of rabbits made atherosclerotic by cholesterol feeding. The cultures consisted of macrophages and smooth muscle cells, thus resembling, in composition, fatty streak lesions. The mean (+/- SD) cholesteryl ester content of the dispersed cells was 1059 +/- 445 micrograms/mg cell protein, but it declined steeply during 1 week in primary culture. The uptake of low-density lipoprotein (LDL), beta-migrating very low-density lipoprotein (beta-VLDL), and acetylated LDL (acetyl-LDL), labeled with 125I or with the fluorescent probe 1,1'-dioctadecyl-3,3,3',3'- tetramethylindocarbocyanine (DiI), was studied in 2-day-old primary cultures. DiI-acetyl-LDL was avidly taken up by the macrophages and, to a lesser extent, by some smooth muscle cells. The uptake of DiI-beta-VLDL by the macrophages was weaker and less homogeneous than that of DiI-acetyl-LDL. The degradation rates of 125I-labeled beta-VLDL, LDL and acetyl-LDL were 135 +/- 54, 195 +/- 20, and 697 +/- 14 ng/mg cell protein/8 hours, respectively. Incubation with unlabeled acetyl-LDL enhanced the incorporation of 3Holeate into cholesteryl esters and increased the cellular cholesteryl ester content. These results suggest that arterial macrophages and, to some extent, smooth muscle cells from cholesterol-fed rabbits actively metabolize acetyl-LDL and are thus capable of accumulating cholesteryl esters by uptake of modified forms of LDL. |
| Lipoprotein desialylation simultaneously enhances the cell cholesterol uptake and impairs the reverse cholesterol transport system: in vitro evidences utilizing neuraminidase-treated lipoproteins and mouse peritoneal macrophages Harada, L. M., M. D. Carvalho, et al. (1998), Atherosclerosis 139(1): 65-75. Abstract: Desialylation of low density lipoprotein (LDL) brings about accumulation of cholesterol in cultured cells. The influence of the neuraminidase-treated lipoprotein (LP) on the reverse cholesterol transport system was investigated in vitro utilizing very low density lipoprotein (VLDL), LDL, total high density lipoprotein (HDL) and its subfractions, HDL2 and HDL3, isolated from healthy donor plasma and mouse peritoneal macrophages. It was found that LP desialylation significantly: (1) decreased the capacity of total HDL and of HDL2, but not of HDL3, to efflux cellular cholesterol; (2) lowered the cholesterol esterification rate by lecithin:cholesterol acyltransferase (LCAT) without modifying the intrinsic LCAT activity of HDL; (3) increased the cholesteryl ester transfer from HDL to apo B-containing LP mediated by cholesteryl ester transfer protein (CETP); (4) enhanced the uptake by macrophages of cholesterol from HDL and LDL, although the amount of cholesterol taken up by the cells was much greater from the desialylated LDL than from desialylated HDL. Taken together, these in vitro evidences indicate that, in addition to enhancing the cell cholesterol LP uptake, desialylation may contribute to the premature development of atherosclerosis by impairing the reverse cholesterol transport system. |
| Lipoprotein enhancement of ovarian theca-interstitial cell steroidogenesis: relative contribution of scavenger receptor class B (type I) and adenosine 5'-triphosphate- binding cassette (type A1) transporter in high-density lipoprotein-cholesterol transport and androgen synthesis Wu, Q., S. Sucheta, et al. (2003), Endocrinology 144(6): 2437-45. Abstract: The theca-interstitial cells take up plasma high-density lipoprotein (HDL)- and low-density-lipoprotein-derived cholesterol to convert into steroid hormones. The uptake of HDL-derived cholesterol is mediated by the scavenger receptor, class B, type I (SR-BI). In nonsteroidogenic cells, HDL-stimulated efflux of cholesterol has been shown to be mediated by the ATP-binding cassette A1 (ABCA1) transporter. Its expression has not been documented in steroidogenic cells. The goal of the present study was to determine: 1) the role of SR-BI in theca-interstitial cell androgen production; 2) whether theca-interstitial cells express ABCA1 transporter mRNA; and 3) the relative roles of SR-BI and ABCA1 transporter in androgen production. The ABCA1 transporter mRNA expression in rat theca-interstitial cells was shown using RT-PCR and Northern blot analyses. The role of SR-BI and ABCA1 in androstenedione production was also examined by treating cells with anti-SR-BI and 2-hydroxypropyl-beta-cyclodextrin in the presence and absence of human chorionic gonadotropin and/or human HDL(3). The treatment of theca-interstitial cells with anti-SR-BI antibody blocked more than 90% of HDL plus human chorionic gonadotropin-stimulated androstenedione production, and selective HDL-CE uptake. On the other hand, the use of inhibitors of ABCA1 transporter function had no discernible effect on HDL-supported androgen production. These data demonstrate that, although theca-interstitial cells express both SR-BI and ABCA1 transporter mRNA, the SR-BI pathway supplies the majority of the cholesterol required for androgen production. Furthermore, the present study presents evidence for a crucial role for SR-BI in HDL-mediated androgen production. |
| Lipoprotein lipase and hepatic lipase activities in a hypercholesterolaemic (RICO) strain of rat. Effect of dietary cholesterol Sultan, F., L. E. Cardona-Sanclemente, et al. (1990), Biochem J 266(2): 349-53. Abstract: Hepatic lipase (HL) and lipoprotein lipase (LPL) were assayed in heparinized plasma from male normocholesterolaemic (SW) and genetically hypercholesterolaemic (RICO) rats. Both strains were fed on either a semi-purified control diet or the same diet enriched with 0.5% or 1% cholesterol. HL activity was similar in both groups of rats fed on the control diet. LPL activity was found to be significantly lower in RICO rats (35% decrease, P less than 0.05). Feeding with a high-cholesterol diet led to a decrease in HL activity (15-23%) in both groups of rats but no change was detected in LPL activity, which remained consistently lower in the RICO rats. Thus, with the control diet, LPL activity is lower in RICO rats but presumably is not rate-limiting for their triacylglycerol clearance, given the normal triacylglycerol levels present. After cholesterol feeding, however, the lower LPL activity may become rate-limiting together with the decrease in HL activity, as in these circumstances hypertriacylglycerolaemia was evident and the hypercholesterolaemia of this strain was further increased. |
| Lipoprotein lipase gene polymorphism, cholesterol subfractions and myocardial infarction in large samples of the general population Holmer, S. R., C. Hengstenberg, et al. (2000), Cardiovasc Res 47(4): 806-12. Abstract: OBJECTIVE: Genetic variants of the lipoprotein lipase gene have been associated with dyslipidemia and coronary artery disease. However, data have been inconsistent and are mainly based on selected predominantly male patient groups. METHODS: We evaluated the influence of the HindIII restriction fragment length polymorphism on lipid levels in the general population (1361 participants of a large population-based survey from Augsburg, Germany; 50% women) as well as the association of this polymorphism with the risk of myocardial infarction (MI; genotype frequencies in 1159 patients with documented MI under 60 years of age). RESULTS: In the population-based survey, a highly significant association between the frequent H2H2 genotype and unfavorable cholesterol subfraction levels was observed in men and in postmenopausal women whereas no significant association was observed in premenopausal women (uni- and multivariate analysis). Such unfavorable lipid levels in homozygotes for the H2 allele may be expected to be associated with a 19-25% increased risk to suffer from myocardial infarction (MI). Nevertheless, genotype and allele frequencies in the general population were not different from those in patients with previous MI (H2H2 genotype frequency 51.3% vs. 53.2%, respectively; P=0.63). CONCLUSION: This large study shows that the H2H2 genotype of the lipoprotein lipase gene polymorphism is associated with unfavorable lipid levels. Estrogen status may modulate this association in women. The effects of the genotype on lipid levels were apparently not strong enough to reveal a significant association with MI. |
| Lipoprotein lipase variants D9N and N291S are associated with increased plasma triglyceride and lower high-density lipoprotein cholesterol concentrations: studies in the fasting and postprandial states: the European Atherosclerosis Research Studies Gerdes, C., R. M. Fisher, et al. (1997), Circulation 96(3): 733-40. Abstract: BACKGROUND: Variations at the DNA level with moderate effects on biochemical variables may be important for the occurrence of disease at the population level, if they are common. Two mutations in the LPL gene, N9 and S291, are associated with variation in fasting plasma concentrations of HDL cholesterol (HDL-C) and triglycerides (TG). We investigated whether these mutants were more frequent in offspring of cases with premature coronary disease and analyzed the effects on fasting plasma lipids and postprandial TG. METHODS AND RESULTS: Students with and without paternal history of myocardial infarction (cases and control subjects controls) were studied in the European Atherosclerosis Research Studies I and II (EARS-I and -II). Allelic frequencies for the N9 and S291 mutations did not differ between cases and control subjects. The N9 mutation was identified in 4.2% of all subjects in EARS-I, and carriers had higher fasting TG levels (P<.001) than noncarriers. In an oral fat tolerance test, there were no differences in postprandial TG between carriers and noncarriers of the N9 allele. The S291 mutation was identified in 3.1% of all subjects in EARS-I, and carriers had lower fasting HDL-C levels (P<.005) than noncarriers. There was a significant interaction between S291 genotype and body mass index on fasting TG levels (P<.01). In the cases, carriers of the S291 allele had higher TG levels 6 hours postprandially (P<.04) than did noncarriers. CONCLUSIONS: The two LPL mutations are common and may predispose to elevated TG and decreased HDL-C concentrations, even in young subjects. In the case of the S291 mutation, this effect appears to be mediated via delayed postprandial TG clearance. Moreover, even moderate obesity potentiates the TG-raising and HDL-lowering effects associated with the S291 allele. |
| Lipoprotein lipid response to the National Cholesterol Education Program step II diet by hypercholesterolemic and combined hyperlipidemic women and men Walden, C. E., B. M. Retzlaff, et al. (1997), Arterioscler Thromb Vasc Biol 17(2): 375-82. Abstract: The beFIT study tested whether teaching the NCEP step II diet (< 30% of calories from total fat and < 7% from saturated fat) is an effective therapy in hypercholesterolemic women and men with or without elevated triglycerides after 6 months. Hypercholesterolemic subjects had two LDL cholesterol measurements above the age- and sex-specific 75th percentile, and combined hyperlipidemic subjects additionally had similarly elevated triglyceride. Subjects were randomized to receive dietary intervention (eight weekly classes) immediately or 6 months later. Follow-up visits were quarterly, with lipid measurements and 4-day food records. Subjects randomized to delayed intervention did not report diet changes or experience lipid changes; the immediate intervention group significantly reduced fat and cholesterol intake, resulting in significant LDL cholesterol lowering. Six months after diet instruction, 178 women and 231 men reported total and saturated fat intakes of approximately 25% and 7.5% kcal LDL cholesterol was significantly reduced in women (7.6% and 8.1%) and men (8.8% and 8.1%) with hypercholesterolemia and combined hyperlipidemia, respectively, but was not different by sex or lipid disorder. Candidates for drug therapy were reduced from between 27% and 37% to 20%. HDL cholesterol was significantly decreased in women (-6.4% and -4.7%) but not in men (-1.3% and -2.7%). The 6.4% reduction in hypercholesterolemic women was significantly different from that of men. The significance of the HDL cholesterol reduction in women is unknown. LDL cholesterol response was similar between women and men and between hypercholesterolemic and combined hyperlipidemic subjects. LDL cholesterol lowering by diet can significantly reduce the number of hyperlipidemic persons requiring drug therapy. |
| Lipoprotein Lp(a) and CETP (cholesterol ester transfer protein): contribution of transgenic mice Chapman, J. and M. Guerin (1994), Bull Acad Natl Med 178(3): 427-34; discussion 434-6. Abstract: Lipoprotein Lp(a) is a pluri-molecular complex rich in cholesterol and composed of an LDL (low-density lipoprotein) particle to which is attached a large glycoprotein, apolipoprotein(a) (apo(a)). Numerous epidemiological studies have established a strong correlation between plasma levels of Lp(a) and the premature development of atheromatous vascular disease in man, an association which has subsequently been confirmed by the detection of Lp(a) in human atherosclerotic plaques. Furthermore, a marked structural resemblance has been demonstrated between apo(a) and plasminogen, a key protein of the fibrinolytic system and responsible for dissolution of blood clots. This discovery has provided evidence, for the first time, that Lp(a) might constitute an important link between atherosclerosis and thrombosis. Intense research effort is now underway to provide further understanding of (I) the structural organisation of the Lp(a) particle; (II) the molecular genetics of apo(a); (III) the processes involved in the synthesis, assembly intravascular metabolism and degradation of Lp(a) and apo(a); (IV) the nature of the interactions of Lp(a) and apo(a) with cellular and non-cellular components of the arterial wall; (V) the role of Lp(a) in fibrinolysis, and (VI) the relationship between Lp(a) and certain metabolic disorders such as familial hypercholesterolemia. These fascinating questions will be examined in the light of studies of different models of transgenic mce expressing human apo(a) alone, or both apo(a) and apo B100. In man, CETP assures the transfer of cholesteryl ester from high-density lipoproteins (HDL) to lipoproteins containing apo-B, and notably VLDL, IDL and LDL.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Lipoprotein Lp(a) as predictor of myocardial infarction in comparison to fibrinogen, LDL cholesterol and other risk factors: results from the prospective Gottingen Risk Incidence and Prevalence Study (GRIPS) Cremer, P., D. Nagel, et al. (1994), Eur J Clin Invest 24(7): 444-53. Abstract: Based on pathophysiological findings Lp(a) is considered to be a cardiovascular risk factor. The Gottingen Risk Incidence and Prevalence Study (GRIPS) provides the possibility to evaluate this impact of Lp(a) on the basis of a large prospective cohort study. GRIPS included 6002 men, aged 40-59.9 years at baseline. Data of a 5 year follow-up period is now available for > 95% of the study participants. Multivariate logistic regression models for the estimation of MI risk confirm Lp(a) as an important risk factor, ranking fifth behind LDL cholesterol, family history of MI, plasma fibrinogen and HDL cholesterol (inversely related). The GRIPS data strongly support strategies for the identification and treatment of persons at increased MI risk which focus on LDL cholesterol. However, Lp(a) and fibrinogen have to be seriously considered as additional risk factors and should be included in diagnostic panels for the estimation of MI risk. |