| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Electron spin resonance studies of phosphatidylcholine interacted with cholesterol and with a hopanoid in liposomal membrane Nagimo, A., Y. Sato, et al. (1991), Chem Pharm Bull (Tokyo) 39(11): 3071-4. Abstract: The effects of bacteriohopane-32-ol (Monol) on liposomal membrane composed of dipalmitoylphosphatidylcholine (DPPC) or egg yolk phosphatidylcholine (egg PC) were compared with those of cholesterol (Chol) in the change of fluidity using a spin label. The fluidity change close to the polar head groups caused by temperature increase in the DPPC membrane containing Monol was different from that of Chol. Chol had a condensing effect on DPPC membrane, whereas Monol had only a slight effect except when used at 20 mol%. Near the hydrophobic end, Chol incorporation into DPPC led to fluidization below transition temperature (Tm) and condensation above Tm. Monol incorporation into DPPC had only a fluidizing effect below Tm. On the other hand, in egg PC membrane Chol had the condensing effect at any temperature, whereas Monol had only slight effect. These results suggest that Monol may have a role in supporting constant membrane fluidity under drastic conditions. |
| Electron transfer to cytochrome P-450scc limits cholesterol-side-chain-cleavage activity in the human placenta Tuckey, R. C., S. T. Woods, et al. (1997), Eur J Biochem 244(3): 835-9. Abstract: The aim of this study was to determine whether electron transfer from adrenodoxin reductase and adrenodoxin limits the activity of cytochrome P-450scc in mitochondria from the human placenta. Mitochondria were disrupted by sonication to enable exogenous adrenodoxin and adrenodoxin reductase to deliver electrons to cytochrome P-450scc. After sonication, the rate of pregnenolone synthesis was greatly decreased relative to that by intact mitochondria, due to dilution of endogenous adrenodoxin and adrenodoxin reductase into the incubation medium. The addition of saturating concentrations of bovine or human adrenodoxin and bovine adrenodoxin reductase to the disrupted mitochondria gave an initial rate of pregnenolone synthesis that was 6.3-fold higher than that for intact mitochondria. Similar results were observed when 20alpha-hydroxycholesterol was used as substrate rather than endogenous cholesterol. The turnover number of cytochrome P-450scc in sonicated placental mitochondria supplemented with adrenodoxin and adrenodoxin reductase was comparable to that for the purified enzyme assayed under conditions where electron transfer was not limiting. Addition of exogenous adrenodoxin and adrenodoxin reductase to sonicated mitochondria from the pig corpus luteum and rat adrenal had a much smaller effect on pregnenolone synthesis compared with intact mitochondria, than observed for the placenta. We conclude that in the human placenta, electron transfer to cytochrome P-450scc is limiting, permitting pregnenolone synthesis to proceed at only 16% maximum velocity. |
| Electron-capture gas chromatography as a sensitive method for measuring subnanogram amounts of cholesterol in saliva and urine Schwertner, H. A., E. R. Johnson, et al. (1990), Clin Chem 36(3): 519-21. Abstract: This is a sensitive method, suitable for measuring subanogram amounts of cholesterol. Cholesterol and the internal standard, epicoprostanol (5-beta-cholestan-3-alpha-ol), are derivatized with pentafluorobenzoyl chloride and detected by electron-capture gas chromatography. The pentafluorobenzoyl esters of cholesterol and the internal standard are easily formed and possess excellent chromatographic and electron-capturing properties. The lower limit of detection of the method, approximately 100 pg injected, is about 500-fold as sensitive as chromatographic methods involving flame-ionization detection. Within-day and between-day coefficients of variation were 4.2% and 8.2%, respectively, for determinations of a urinary cholesterol concentration of 570 micrograms/L (1.47 mumol/L). Such sensitivity permits analysis for cholesterol in (e.g.) physiological fluids, tissue samples, and cell cultures that contain very low concentrations of cholesterol. |
| Electronic and stereochemical characterizations of intermediates in the photolysis of ferric cytochrome P450scc nitrosyl complexes. Effects of cholesterol and its analogues on ligand binding structures Hori, H., F. Masuya, et al. (1992), J Biol Chem 267(26): 18377-81. Abstract: Low temperature photolysis of nitric oxide from the nitrosyl complexes of ferric cytochrome P450scc was examined by EPR spectroscopy to elucidate the stereochemical interaction between heme-bound ligand and side-chain of cholesterol or its hydroxylated analogues at the substrate-binding site. The photoproducts of the NO complexes trapped at 5 K exhibited new EPR absorptions providing information on the steric crowding of the distal heme moiety. Without substrate, the photoproduct exhibited a broad EPR absorption at g-8 due to magnetic dipole-dipole interaction between the photo-dissociated NO (S = 1/2) and the ferric iron (S = 5/2). This indicates that the photo-dissociated NO can move far away from the heme iron in the less restricted distal heme moiety of the substrate-free cytochrome P450scc. In the presence of substrates, such as cholesterol, 20(S)-hydroxycholesterol, 22(S)-hydroxycholesterol, 22(R)-hydroxycholesterol, and 25-hydroxycholesterol, the EPR spectra of the photoproducts exhibited many variations having broad g-8 absorptions and/or the widespread signals together with zero-field absorption. Among the steroid complexes used, 20(S)-hydroxycholesterol complex exhibited a conspicuously widespread EPR signal with a distinct zero-field absorption due to a spin-coupled interaction between the ferric iron (S = 5/2) and the photolyzed NO (S = 1/2). These results indicate that the 20(S)-hydroxycholesterol complex has restricted substrate-binding structure and that the hydroxylation of the cholesterol side-chain at the 22R position is necessary to proceed the side-chain cleavage reaction properly in cytochrome P450scc. |
| Electrophoresis and the traditional method for the measurement of lipoprotein cholesterol in serum Wang, J. G. and X. S. Xie (2002), Hunan Yi Ke Da Xue Xue Bao 27(1): 51-4. Abstract: OBJECTIVE: To compare the advantages and disadvantages of electrophoresis with the traditional method in measuring lipoprotein cholesterol in serum. METHODS: Four lipoprotein cholesterols were determined by the Helena electrophoretic system. Quantification of high density lipoprotein-choleterol(HDL-C) was performed by phosphotungstate-magnesium precipitation or direct HDL-C assay. The concentration of low density lipoprotein-cholesterol (LDL-C) was calculated by F-equation. RESULTS: Four lipoprotein zones were segregated distinctly by the electrophoretic method. Lp(a) zone appeared only in 6 out of 68 normal samples (8.82%). Reference values of HDL-C, Lp(a)-C, VLDL-C, and LDL-C in serum were 1.16-2.19, 0-0.22, 0.07-0.47, and 1.86-3.46 mmol.L-1, respectively. When comparing the results by electrophoresis with those by the precipitation method for HDL-C, no significant difference was found (P > 0.05); but there was a significant difference between electrophoresis and F-formula calculation for LDL-C (P < 0.05). When comparing results of electrophoresis with the direct method, we found significant differences in both HDL-C and LDL-C (P < 0.01). CONCLUSION: F-formula used for calculating LDL-C is not appropriate to clinical application. Electrophoresis allows the quantification of HDL-C, VLDL-C, LP(a)-C, and LDL-C. The method is simple, convenient, and appropriate to routine application. |
| Electrophoresis in the quantitative determination of cholesterol in lipoprotein fractions and its clinical application Xu, Z. M., S. P. Zhao, et al. (2002), Hunan Yi Ke Da Xue Xue Bao 27(3): 250-2. Abstract: OBJECTIVE: To evaluate the clinical application of the electrophoresis method for measuring serum cholesterol in lipoproteins and to study the characteristics of lipoprotein fractions in patients with the acute coronary syndrome. METHODS: Cholesterol in lipoprotein fractions in fasting serum was measured by electrophoresis in 26 patients with the acute coronary syndrome and 20 patients with stable angina pectoris. The results were compared to cholesterol in lipoproteins measured with the regular method. RESULTS: There was a good correlation between the methods with coefficients of 0.922, 0.909, and 0.899 for LDL-C, HDL-C and VLDL-C, respectively. The serum levels of TG and VLDL-C in the patients with the acute coronary syndrome were significantly higher than those with stable angina pectoris (0.47 +/- 0.33) mmol.L-1 vs. (0.29 +/- 0.19) mmol.L-1, P < 0.01, (1.82 +/- 0.70) mmol.L-1 vs. (1.31 +/- 0.48) mmol.L-1, P < 0.01. CONCLUSION: The electrophoresis method for quantifying cholesterol in lipoprotein fractions is well correlated with the regular method. The serum levels of VLDL-C and TG in patients with the acute conronary syndrome are higher than those with stable angina. |
| Electrophoretic measurement of lipoprotein(a) cholesterol in plasma with and without ultracentrifugation: comparison with an immunoturbidimetric lipoprotein(a) method Baudhuin, L. M., S. J. Hartman, et al. (2004), Clin Biochem 37(6): 481-8. Abstract: OBJECTIVES: Elevated plasma lipoprotein(a) Lp(a) is a significant risk factor for vascular disease. Standardization of Lp(a) mass measurement is complicated by the heterogeneity of apolipoprotein(a) apo(a). We investigated whether Lp(a) cholesterol measurement, which is not influenced by apo(a) size, is a viable alternative to measuring Lp(a) mass. DESIGN AND METHODS: Plasma Lp(a) cholesterol was measured electrophoretically, with and without ultracentrifugation, and results were compared to each other and to immunoturbidimetrically measured Lp(a) mass in 470 subjects. RESULTS: Ultracentrifuged and whole plasma Lp(a) cholesterol levels demonstrated high correlation (R = 0.964). All samples with detectable (>/=2.0 mg/dl) Lp(a) cholesterol had Lp(a) mass >30 mg/dl (the clinically relevant cutpoint), while 59 samples with Lp(a) mass >30 mg/dl did not have detectable Lp(a) cholesterol. CONCLUSIONS: Lp(a) cholesterol can be measured in whole plasma without interference from VLDL lipoproteins. The relative clinical merits of measuring Lp(a) cholesterol vs. Lp(a) mass or both in combination deserves investigation. |
| Elevated apolipoprotein B-48 and remnant-like particle-cholesterol in heterozygous familial hypercholesterolaemia Dane-Stewart, C. A., G. F. Watts, et al. (2001), Eur J Clin Invest 31(2): 113-7. Abstract: Apolipoprotein B-48 (apoB-48) is a marker of triglyceride-rich lipoprotein (TRL) remnants of intestinal origin. Chylomicron remnants are causally related to atherosclerosis. We have shown previously that fasting plasma apoB-48 may predict postprandial lipaemia. Remnant-like particle-cholesterol (RLP-C) may also reflect TRL remnants. We aimed to determine whether subjects with heterozygous familial hypercholesterolaemia (FH) had an accumulation of remnants of intestinal origin, as reflected by fasting plasma apoB-48 and RLP-C levels. The fasting plasma concentrations of apoB-48 and RLP-C were measured in 15 subjects with heterozygous FH and 15 age- and sex-matched, normolipidaemic subjects. ApoB-48 was determined using SDS-PAGE and a western blotting/enhanced chemi-luminescence technique. RLP-C was measured using an immuno-separation assay. Serum apolipoprotein B-100 (apoB-100) levels were measured using immunonephelometry; lipids were assayed enzymatically. Compared with controls, FH subjects had significantly elevated plasma concentrations of apoB-48 (29.3 median, 16.7-45.1 mg L-1 range vs. 12.8, 7.3-28.6; P < 0.001) and RLP-C (16.2, 1.5-114.3 mg dL-1 vs. 8.5, 5.0-13.5; P = 0.003), as well as serum total apoB-100 (1.9, 1.3-2.6 g L-1 vs. 1.0, 0.3-1.3; P < 0.001), LDL-cholesterol (8.1, 4.6-10.4 mmol L-1 vs. 3.5, 2.4-4.4; P < 0.001) and triglyceride (1.5, 0.6-5.6 mmol L-1 vs. 1.0, 0.4-1.8; P = 0.018). There was no significant difference in HDL cholesterol. The findings suggest that patients with heterozygous FH have elevated plasma concentrations of TRL remnants, including those of intestinal origin. This may be a consequence of decreased clearance of these particles by the LDL-receptor. |
| Elevated blood cholesterol and the prevention of heart disease MacLean, D. R. and A. Chockalingam (1999), Can J Cardiol 15(4): 407-8. |
| Elevated cholesterol and decreased sterol carrier protein-2 in peroxisomes from AS-30D hepatoma compared to normal rat liver Lyons, H. T., A. Kharroubi, et al. (1991), Arch Biochem Biophys 285(2): 238-45. Abstract: Peroxisomes were isolated from AS-30D hepatoma and compared to normal rat liver cells for the purpose of investigating the cholesterol accumulation in the hepatoma cells. Cholesterol was found to be approximately 10-fold higher relative to protein in AS-30D peroxisomes as compared to peroxisomes from normal liver. The peroxisomes from the hepatoma cells were found to be more stable; catalase was not released from these peroxisomes during isolation or osmotic shock of the peroxisomal fraction. The elevated cholesterol level may stabilize the peroxisomal membrane. Sterol carrier protein-2 (SCP-2) levels were measured using a radioimmunoassay (RIA), which indicated the highest concentration of SCP-2 to be in peroxisomes. Hepatoma peroxisomes had a lower concentration of SCP-2 (2.5 micrograms/mg) than normal liver peroxisomes (8 micrograms/mg). Approximately half of all SCP-2 detected was found to be soluble in both hepatoma and normal rat liver cells. Immunoblots from both rat liver and AS-30D fractions demonstrated the presence of the 14-kDa form of SCP-2. The liver fractions also had a 57-kDa immunoreactive protein, which was barely detectable in the AS-30D fractions. The low abundance of the high molecular weight form of SCP-2 from hepatoma peroxisomes and the lower amounts of SCP-2 detected in the AS-30D peroxisomes may be related to the accumulation of cholesterol in the cells. |
| Elevated cholesterol levels associated with nonresponse to fluoxetine treatment in major depressive disorder Sonawalla, S. B., G. I. Papakostas, et al. (2002), Psychosomatics 43(4): 310-6. Abstract: Previous studies have suggested that patients with major depressive disorder may have lower cholesterol levels compared to healthy controls. The purpose of this study was to examine the relationship between pretreatment serum cholesterol levels and clinical response to treatment with fluoxetine among outpatients with major depression. Three hundred and twenty-two depressed outpatients meeting DSM-III-R criteria for major depressive disorder were enrolled in an 8-week, fixed-dose, open trial of fluoxetine 20 mg/day. Nonfasting serum cholesterol levels were obtained for all patients before starting fluoxetine. All patients were drug free for a minimum of 2 weeks prior to the onset of the study. Clinical response was defined as a 50% or greater decrease in the 17-item Hamilton Rating Scale for Depression (HAM-D-17) score at endpoint compared to baseline. Cholesterol levels were classified as either elevated (defined as a level equal to or greater than 200 mg/dL) or nonelevated (defined as a level less than 200 mg/dL). Among the 322 outpatients, 51.6% were classified as having elevated and 48.4% as having nonelevated cholesterol levels at baseline (mean cholesterol level 238.6 +/- 33.4 mg/dL vs. 170.4 +/- 22.2 mg/dL, respectively). Depressed patients with elevated cholesterol levels did not significantly differ in gender ratio but were significantly older than depressed patients with nonelevated cholesterol levels (P <.0001). After adjusting for age, gender, and Body Mass Index (BMI), depressed patients with elevated cholesterol levels were significantly more likely to be nonresponders to fluoxetine treatment than were depressed patients with nonelevated cholesterol levels (P < 0.05). Elevated serum cholesterol levels appear to be associated with poorer response to fluoxetine treatment. Further studies are needed to confirm our findings. |
| Elevated cholesterol levels. How to individualize treatment Potts, J. F. and P. A. Setness (1990), Postgrad Med 88(3): 233-9. Abstract: Each of the three case studies represents a common presentation of a patient with elevated lipid levels. By categorizing patients using the guidelines of the National Cholesterol Education Program and considering the high-density lipoprotein cholesterol level, clinicians can more reliably assess response to treatment. An elevated total cholesterol level is only one of several important risk factors for coronary artery disease that must be confronted. |
| Elevated cholesterol metabolism and bile acid synthesis in mice lacking membrane tyrosine kinase receptor FGFR4 Yu, C., F. Wang, et al. (2000), J Biol Chem 275(20): 15482-9. Abstract: Heparan sulfate-regulated transmembrane tyrosine kinase receptor FGFR4 is the major FGFR isotype in mature hepatocytes. Fibroblast growth factor has been implicated in the definition of liver from foregut endoderm where FGFR4 is expressed and stimulation of hepatocyte DNA synthesis in vitro. Here we show that livers of mice lacking FGFR4 exhibited normal morphology and regenerated normally in response to partial hepatectomy. However, the FGFR4 (-/-) mice exhibited depleted gallbladders, an elevated bile acid pool and elevated excretion of bile acids. Cholesterol- and bile acid-controlled liver cholesterol 7alpha-hydroxylase, the limiting enzyme for bile acid synthesis, was elevated, unresponsive to dietary cholesterol, but repressed normally by dietary cholate. Expression pattern and cholate-dependent, cholesterol-induced hepatomegaly in the FGFR4 (-/-) mice suggested that activation of receptor interacting protein 140, a co-repressor of feed-forward activator liver X receptor alpha, may mediate the negative regulation of cholesterol- and bile acid-controlled liver cholesterol 7alpha-hydroxylase transcription by FGFR4 and cholate. The results demonstrate that transmembrane sensors interface with metabolite-controlled transcription networks and suggest that pericellular matrix-controlled liver FGFR4 in particular may ensure adequate cholesterol for cell structures and signal transduction. |
| Elevated HDL cholesterol is a risk factor for ischemic heart disease in white women when caused by a common mutation in the cholesteryl ester transfer protein gene Agerholm-Larsen, B., B. G. Nordestgaard, et al. (2000), Circulation 101(16): 1907-12. Abstract: BACKGROUND: The level of HDL cholesterol is inversely related to the risk of ischemic heart disease. METHODS AND RESULTS: In 9168 women and men from a general population and 946 women and men with ischemic heart disease (all white), we tested the hypothesis that the Ile405Val mutation in the cholesteryl ester transfer protein gene (CETP) affects HDL cholesterol levels and the risk of ischemic heart disease. The relative frequencies of Ile/Ile, Ile/Val, and Val/Val carriers were 0.46, 0.43, and 0.11 for both women and men. Women with these 3 genotypes had mean HDL cholesterol levels of 1.68, 1.75, and 1.82 mmol/L, respectively (P<0.001, ANOVA), as well as a significant decrease in the ratio of total to HDL cholesterol (P=0. 002, ANOVA). On multiple logistic regression analysis, women not treated with hormone replacement therapy who were heterozygous or homozygous for Val405 had a 1.4-fold (95% CI 1.0 to 1.9) to 2.1-fold (95% CI 1.3 to 3.4) increase in the risk of ischemic heart disease. No significant associations were found in men. CONCLUSIONS: Increased HDL cholesterol levels caused by mutations in CETP are associated with an increased risk of ischemic heart disease in white women. |
| Elevated high-density lipoprotein cholesterol and dietary fat intake in women with cyclic mastopathy Goodwin, P. J., A. Miller, et al. (1998), Am J Obstet Gynecol 179(2): 430-7. Abstract: OBJECTIVE: This study was designed to examine the contribution of plasma lipids to the pathophysiology of cyclic mastopathy, before and after consideration of diet and sex hormones. STUDY DESIGN: Thirty-four women with severe cyclic mastopathy (case patients) and 29 women without cyclic mastopathy (control subjects) recorded their breast symptoms daily during 1 menstrual cycle. During each menstrual phase (follicular, early luteal, late luteal, and menstrual) they prospectively completed 2 24-hour dietary diaries, provided blood for lipid and hormone assays, and underwent anthropometric measurements. RESULTS: Mean age was 34 years. Premenstrual breast swelling and tenderness were significantly more severe in case patients (P <.0001). Cyclic change (late luteal vs follicular) of high-density lipoprotein cholesterol differed between case patients and control subjects, with case patients having a relative excess of high-density lipoprotein cholesterol in the premenstrual phase (P =.01). Dietary fat intake was greater throughout the cycle in case patients (37.5 vs 33.7% of calories, P =.02), and case patients reported increased appetite in the premenstrual phase (P =.01). In multivariate analyses the contributions of mean dietary fat intake and of cyclic change in high-density lipoprotein cholesterol were independently significant, with odds ratios for upper versus lower quintiles being slightly >5. CONCLUSIONS: Women with cyclic mastopathy had a relative excess of high-density lipoprotein cholesterol during the symptomatic late luteal phase of the menstrual cycle and a higher fat intake throughout the cycle than did control subjects. These observations support the hypothesis that lipids (notably high-density lipoprotein cholesterol) and a high-fat diet play a role in the pathophysiologic characteristics of cyclic mastopathy. |
| Elevated high-density lipoprotein cholesterol, not protective in the presence of homocysteinemia Superko, H. R. (1997), Am J Cardiol 79(5): 705-6. Abstract: Elevated high-density lipoprotein cholesterol is considered a protective factor for atherosclerosis. Very high density lipoprotein cholesterol is not necessarily protective in the setting of elevated plasma homocysteine concentrations. |
| Elevated high-density-lipoprotein cholesterol and normal triglycerides as markers of longevity Nikkila, M., T. Pitkajarvi, et al. (1991), Klin Wochenschr 69(17): 780-5. Abstract: Serum cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides of 85 year old home-living persons were compared to those of controls and of patients who had severe coronary artery disease (CAD) at an early age. Eighty-five-year-olds had higher serum HDL cholesterol than controls and patients with CAD. Patients with severe CAD had higher serum total cholesterol and serum triglycerides and lower HDL-cholesterol than other groups. When 85-year-old persons were divided into quintiles according to serum HDL cholesterol, women with highest HDL cholesterol had lowest mortality, men with lowest HDL cholesterol had highest mortality. We conclude that elevated HDL cholesterol is correlating with longevity and low HDL cholesterol with CAD at an early age. |
| Elevated levels of low-density lipoprotein cholesterol, homocysteine, and lipoprotein(a) are associated with the occurrence of symptomatic bypass graft disease 1 year following coronary artery bypass graft surgery Harris, M., N. W. Shammas, et al. (2004), Prev Cardiol 7(3): 106-8. Abstract: Severe coronary artery bypass graft disease occurs at a rate of approximately 16%-31% within the first year of surgery. Clinical and laboratory variables, including postoperative lipid profiles closest to the 1-year follow-up, lipoprotein(a) levels, and homocysteine levels, were assessed as predictors of early (< or = 1 year) symptomatic coronary artery bypass graft disease. Of 77 living consecutive patients (from the practice of one cardiologist) who underwent bypass surgery, 60 were asymptomatic at 1 year, and 17 had developed recurrent symptoms and had an angiogram that confirmed >50% lesion in at least one saphenous bypass graft. Using multivariate analysis, the strongest predictors of early symptomatic coronary artery bypass graft disease within 1 year of bypass surgery were elevated levels of low-density lipoprotein cholesterol (>100 mg/dL) (odds ratio OR, 8:1; p=0.034), homocysteine (>10 micromol/L) (OR, 8:1; p=0.019), and lipoprotein(a) (>30 mg/dL) (OR, 4:1; p=0.011). Male gender was associated with a reduced risk (OR, 1:9; p=0.01) of symptomatic graft disease within 1 year of surgery. The authors conclude that low-density lipoprotein, homocysteine, and lipoprotein(a) levels are associated with symptomatic coronary artery bypass graft disease at 1 year after surgery. |
| Elevated levels of SREBP-2 and cholesterol synthesis in livers of mice homozygous for a targeted disruption of the SREBP-1 gene Shimano, H., I. Shimomura, et al. (1997), J Clin Invest 100(8): 2115-24. Abstract: The synthesis of cholesterol and its uptake from plasma LDL are regulated by two membrane-bound transcription factors, designated sterol regulatory element binding protein-1 and -2 (SREBP-1 and SREBP-2). Here, we used the technique of homologous recombination to generate mice with disruptions in the gene encoding the two isoforms of SREBP-1, termed SREBP-1a and SREBP-1c. Heterozygous gene-disrupted mice were phenotypically normal, but 50- 85% of the homozygous (-/-) mice died in utero at embryonic day 11. The surviving -/- mice appeared normal at birth and throughout life. Their livers expressed no functional SREBP-1. There was a 1.5-fold upregulation of SREBP-2 at the level of mRNA and a two- to threefold increase in the amount of mature SREBP-2 in liver nuclei. Previous studies showed that SREBP-2 is much more potent than SREBP-1c, the predominant hepatic isoform of SREBP-1, in activating transcription of genes encoding enzymes of cholesterol synthesis. Consistent with this observation, the SREBP-1 -/- animals manifested elevated levels of mRNAs for 3-hydroxy-3-methylglutaryl coenzyme A synthase and reductase, farnesyl diphosphate synthase, and squalene synthase. Cholesterol synthesis, as measured by the incorporation of 3Hwater, was elevated threefold in livers of the -/- mice, and hepatic cholesterol content was increased by 50%. Fatty acid synthesis was decreased in livers of the -/- mice. The amount of white adipose tissue was not significantly decreased, and the levels of mRNAs for lipogenic enzymes, adipocyte lipid binding protein, lipoprotein lipase, and leptin were normal in the -/- mice. We conclude from these studies that SREBP-2 can replace SREBP-1 in regulating cholesterol synthesis in livers of mice and that the higher potency of SREBP-2 relative to SREBP-1c leads to excessive hepatic cholesterol synthesis in these animals. |
| Elevated lipoprotein(a) is lowered by a cholesterol synthesis inhibitor in a normocholesterolaemic patient with premature myocardial infarction Schmidt, H. H., S. Wagner, et al. (1993), Blood Coagul Fibrinolysis 4(1): 173-5. Abstract: We have identified a 37-year-old patient suffering from two myocardial infarctions, with a markedly elevated lipoprotein(a) Lp(a) level and normal levels of cholesterol and triglycerides. Clinically this patient presented with xanthelasma and arcus lipoides corneae. After treatment with a cholesterol synthesis inhibitor (Pravastatin), the Lp(a) concentration in this patient was reduced significantly. This case report supports the hypothesis that elevated Lp(a) is an independent risk factor for coronary artery disease. The effect of the cholesterol synthesis inhibitor on Lp(a) may be due to the upregulation of the LDL-receptor, suggesting a role for LDL receptor in Lp(a) catabolism. |