| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene Loftus, S. K., J. A. Morris, et al. (1997), Science 277(5323): 232-5. Abstract: An integrated human-mouse positional candidate approach was used to identify the gene responsible for the phenotypes observed in a mouse model of Niemann-Pick type C (NP-C) disease. The predicted murine NPC1 protein has sequence homology to the putative transmembrane domains of the Hedgehog signaling molecule Patched, to the cholesterol-sensing regions of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and SREBP cleavage-activating protein (SCAP), and to the NPC1 orthologs identified in human, the nematode Caenorhabditis elegans, and the yeast Saccharomyces cerevisiae. The mouse model may provide an important resource for studying the role of NPC1 in cholesterol homeostasis and neurodegeneration and for assessing the efficacy of new drugs for NP-C disease. |
| Must we change our traditional units for cholesterol? Ellison, R. C. (1990), N Engl J Med 322(3): 207-8. |
| Mutation in the ARH gene and a chromosome 13q locus influence cholesterol levels in a new form of digenic-recessive familial hypercholesterolemia Al-Kateb, H., S. Bahring, et al. (2002), Circ Res 90(9): 951-8. Abstract: We studied a Syrian family with 3 children who had low-density lipoprotein cholesterol (LDL) concentrations of 13.3, 12.2, and 8.6 mmol/L, respectively. Three other siblings and the parents all had LDL values <4.52 mmol/L, suggesting an autosomal-recessive mode of inheritance. The extended pedigree had 66 additional persons with normal LDL values. A genome-wide scan in the core family with 427 markers showed support for linkage on both chromosomes 1 and 13. Markers on chromosome 1 revealed a 3.07 multipoint LOD score between 1p36.1-p35, an 18-cM interval. Surprisingly, we also found linkage to 13q22-q32, a 14-cM interval, with a 3.08 LOD score. We had identified this locus earlier as containing a gene strongly influencing LDL in another Arab family with autosomal-dominant familial hypercholesterolemia and in normal dizygotic twins. We found evidence for an interaction between these loci. We next genotyped our twin panel and confirmed linkage of the 1p36.1-p35 locus to LDL (P<0.002) in this normal population. Elucidation of ARH, the LDL receptor adaptor protein at chromosome 1p35, caused us to sequence that gene. We first identified the genomic structure of ARH gene and then sequenced the gene in our family. We found an intron 1 acceptor splice-site mutation. This mutation was not found in any other family members, in 31 nonrelated Syrian persons, or in 30 Germans. Our results underscore the importance of ARH on chromosome 1 and the chromosome 13q locus to LDL, not only in families with unusual illnesses, but also to the general population. |
| Mutational analysis of human hydroxysteroid sulfotransferase SULT2B1 isoforms reveals that exon 1B of the SULT2B1 gene produces cholesterol sulfotransferase, whereas exon 1A yields pregnenolone sulfotransferase Fuda, H., Y. C. Lee, et al. (2002), J Biol Chem 277(39): 36161-6. Abstract: As a result of an alternative exon 1, the gene for human hydroxysteroid sulfotransferase (SULTB1) encodes for two peptides differing only at their amino termini. The SULT2B1b isoform preferentially sulfonates cholesterol. Conversely, the SULT2B1a isoform avidly sulfonates pregnenolone but not cholesterol. The outstanding structural feature that distinguishes the SULT2B1 isoforms from the prototypical SULT2A1 isozyme is the presence of extended amino- and carboxyl-terminal ends in the former. Investigating the functional significance of this unique characteristic reveals that removal of 53 amino acids from the relatively long carboxyl-terminal end that is common to both SULT2B1 isoforms has no effect on the catalytic activity of either isoform. On the other hand, removal of 23 amino acids from the amino-terminal end that is unique to SULT2B1b results in loss of cholesterol sulfotransferase activity, whereas removal of 8 amino acids from the amino-terminal end that is unique to SULT2B1a has no effect on pregnenolone sulfotransferase activity. Deletion analysis along with site-directed mutagenesis of SULT2B1b reveal that the amino acid segment 19-23 residues from the amino terminus and particularly isoleucines at positions 21 and 23 are crucial for cholesterol catalysis. In the gene for SULT2B1, exon 1B encodes for only the unique amino-terminal region of SULT2B1b; however, exon 1A encodes for the unique amino-terminal end of SULT2B1a plus an additional 48 amino acids. Thus, if the gene for SULT2B1 employs exon 1B, cholesterol sulfotransferase is synthesized, whereas if exon 1A is used, pregnenolone sulfotransferase is produced. |
| Mutations and variants of apolipoprotein B that affect plasma cholesterol levels Innerarity, T. L. and K. Bostrom (1991), Adv Exp Med Biol 285: 25-31. Abstract: Apolipoprotein (apo-) B100 is the exclusive apolipoprotein of low density lipoproteins (LDL0, which transport most of the plasma cholesterol in humans. Mutations in apo-B100 can cause either hypocholesterolemia or hypercholesterolemia. Familial hypobetalipoproteinemia, which leads to hypocholesterolemia, has been shown to be caused by defects in the apo-B gene that terminate translation prematurely and result in the production of truncated proteins. The mutations responsible for the hypocholesterolemia have been either single nucleotide substitutions or deletions. Familial defective apo-B100, which leads to hypercholesterolemia, is caused by a point mutation in the receptor-binding domain of apo-B100. The mutation disrupts the binding of LDL to the LDL receptor, thereby disrupting LDL receptor-mediated catabolism and resulting in hypercholesterolemia. A variant form of apo-B, apo-B48, is also critical for lipoprotein metabolism. Apolipoprotein B48 is obligatory for the secretion of chylomicrons. It is formed from an RNA-edited apo-B mRNA in which codon 2153 has been converted from a CAA (glutamine) codon to a premature UAA (stop) codon. The first cytosine in this codon is deaminated to form uracil. The minimum nucleotide recognition sequence for the editing mechanism has been reported to be between 26 and more than 63 nucleotides surrounding codon 2153. The apo-B mRNA editing mechanism, which appears to be a cytosine deaminase, and its regulation are being actively investigated. |
| Mutations in the 3beta-hydroxysterol Delta24-reductase gene cause desmosterolosis, an autosomal recessive disorder of cholesterol biosynthesis Waterham, H. R., J. Koster, et al. (2001), Am J Hum Genet 69(4): 685-94. Abstract: Desmosterolosis is a rare autosomal recessive disorder characterized by multiple congenital anomalies. Patients with desmosterolosis have elevated levels of the cholesterol precursor desmosterol, in plasma, tissue, and cultured cells; this abnormality suggests a deficiency of the enzyme 3beta-hydroxysterol Delta24-reductase (DHCR24), which, in cholesterol biosynthesis, catalyzes the reduction of the Delta24 double bond of sterol intermediates. We identified the human DHCR24 cDNA, by the similarity between the encoded protein and a recently characterized plant enzyme--DWF1/DIM, from Arabidopsis thaliana--catalyzing a different but partially similar reaction in steroid/sterol biosynthesis in plants. Heterologous expression, in the yeast Saccharomyces cerevisiae, of the DHCR24 cDNA, followed by enzyme-activity measurements, confirmed that it encodes DHCR24. The encoded DHCR24 protein has a calculated molecular weight of 60.1 kD, contains a potential N-terminal secretory-signal sequence as well as at least one putative transmembrane helix, and is a member of a recently defined family of flavin adenine dinucleotide (FAD)-dependent oxidoreductases. Conversion of desmosterol to cholesterol by DHCR24 in vitro is strictly dependent on reduced nicotinamide adenine dinucleotide phosphate and is increased twofold by the addition of FAD to the assay. The corresponding gene, DHCR24, was identified by database searching, spans approximately 46.4 kb, is localized to chromosome 1p31.1-p33, and comprises nine exons and eight introns. Sequence analysis of DHCR24 in two patients with desmosterolosis revealed four different missense mutations, which were shown, by functional expression, in yeast, of the patient alleles, to be disease causing. Our data demonstrate that desmosterolosis is a cholesterol-biosynthesis disorder caused by mutations in DHCR24. |
| Mutations in the ABC1 gene in familial HDL deficiency with defective cholesterol efflux Marcil, M., A. Brooks-Wilson, et al. (1999), Lancet 354(9187): 1341-6. Abstract: BACKGROUND: A low concentration of HDL cholesterol is the most common lipoprotein abnormality in patients with premature atherosclerosis. We have shown that Tangier disease, a rare and severe form of HDL deficiency characterised by a biochemical defect in cellular cholesterol efflux, is caused by mutations in the ATP-binding-cassette (ABC1) gene. This gene codes for the cholesterol-efflux regulatory protein (CERP). We investigated the presence of mutations in this gene in patients with familial HDL deficiency. METHODS: Three French-Canadian families and one Dutch family with familial HDL deficiency were studied. Fibroblasts from the proband of each family were defective in cellular cholesterol efflux. Genomic DNA of each proband was used for mutation detection with primers flanking each exon of the ABC1 gene, and for sequencing of the entire coding region of the gene. PCR and restriction-fragment length polymorphism assays specific to each mutation were used to investigate segregation of the mutation in each family, and to test for absence of the mutation in DNA from normal controls. FINDINGS: A different mutation was detected in ABC1 in each family studied. Each mutation either created a stop codon predicted to result in truncation of CERP, or altered a conserved aminoacid residue. Each mutation segregated with low concentrations of HDL-cholesterol in the family, and was not observed in more than 500 control chromosomes tested. INTERPRETATION: These data show that mutations in ABC1 are the major cause of familial HDL deficiency associated with defective cholesterol efflux, and that CERP has an essential role in the formation of HDL. Our findings highlight the potential of modulation of ABC1 as a new route for increasing HDL concentrations. |
| Mutations in the gene for lipoprotein lipase. A cause for low HDL cholesterol levels in individuals heterozygous for familial hypercholesterolemia Pimstone, S. N., S. E. Gagne, et al. (1995), Arterioscler Thromb Vasc Biol 15(10): 1704-12. Abstract: Familial hypercholesterolemia (FH) is characterized by elevated plasma concentrations of LDL cholesterol resulting from mutations in the gene for the LDL receptor. Low HDL cholesterol levels are seen frequently in patients both heterozygous and homozygous for mutations in this gene. Suggested mechanisms for reduced HDL levels in FH patients have been altered apolipoprotein A-1 metabolism and elevated cholesteryl ester transfer protein activity, but the molecular basis for hypoalphalipoproteinemia in any of these patients has not yet been identified. We investigated four large families in which individuals were found to be double heterozygotes for both FH and lipoprotein lipase (LPL) deficiency. These double heterozygotes have significantly less HDL cholesterol than persons with FH or LPL heterozygosity alone. In the double heterozygotes, HDL particle composition is not significantly different from FH heterozygotes, suggesting a quantitative rather than qualitative defect in HDL metabolism in these persons. We propose that mutations in the LPL gene may be a cause of low HDL cholesterol levels in some individuals heterozygous for FH. |
| Mutations of low-density-lipoprotein-receptor gene, variation in plasma cholesterol, and expression of coronary heart disease in homozygous familial hypercholesterolaemia Moorjani, S., M. Roy, et al. (1993), Lancet 341(8856): 1303-6. Abstract: Variation in plasma-cholesterol concentration and the expression of coronary heart disease in patients with homozygous familial hypercholesterolaemia (FH) is well documented, but the underlying reasons for variation are not clearly defined. Because FH is caused by mutations at the low-density-lipoprotein-gene locus, we compared plasma-cholesterol concentrations in 21 FH homozygotes with either the greater than 10 kb deletion (promoter region and exon 1) (11 subjects) or the exon 3 missense (trp66-->gly) mutation (10 subjects) of the low-density-lipoprotein gene. Subjects with the greater than 10 kb deletion had a higher mean plasma-cholesterol concentration than those with the exon 3 mutations (26.7 vs 16.1 mmol/L; p = 0.000006), and there was no overlap in individual plasma-cholesterol concentrations between subjects in the two groups. Although the frequency of coronary heart disease was similar in the two groups, age-of-onset was earlier in subjects with the greater than 10 kb deletion (p = 0.059). Also, coronary deaths were more frequent (p = 0.044) and occurred at an earlier age (p = 0.009) in subjects with the greater than 10 kb deletion. Our results provide evidence that there is less variation in plasma-cholesterol concentrations among FH homozygotes when they are subdivided into groups according to low-density-lipoprotein-receptor-gene defect. Furthermore, differences in plasma-cholesterol concentrations are reflected in the severity of coronary heart disease expression. |
| Mutations of the peroxisome proliferator-activated receptor gamma (PPAR gamma) gene in a Japanese population: the Pro12Ala mutation in PPAR gamma 2 is associated with lower concentrations of serum total and non-HDL cholesterol Iwata, E., H. Matsuda, et al. (2001), Diabetologia 44(10): 1354-5. |
| Mycophenolate mofetil treatment reduces atherosclerosis in the cholesterol-fed rabbit Greenstein, S. M., S. Sun, et al. (2000), J Surg Res 91(2): 123-9. Abstract: Immune/inflammatory responses of arterial vessel wall constituents to lipid metabolic disturbances have been postulated to contribute to the pathogenesis of atherosclerosis. Mycophenolate mofetil (MMF), an antiproliferative agent used in clinical transplantation, has been shown to inhibit smooth muscle cell (SMC) proliferation and decrease the recruitment of monocytes into sites of chronic inflammation. This study was conducted to determine the effect of MMF on atherosclerotic plaque development after cholesterol-induced injury. New Zealand white rabbits were fed a high-cholesterol diet containing 0.5% cholesterol and 8% peanut oil. The experimental group (n = 10) was given MMF (80 mg/kg/day subcutaneously); the control group (n = 10) received placebo injections. The aortas were harvested at 12 weeks for immunohistochemical analyses. SMCs were identified by reactivity with a monoclonal antibody (mAb) to alpha smooth muscle actin. Monocytes/macrophages were detected with mAb RAM 11. Cross-sectional areas of the media and neointima were measured using computer-assisted image analysis. The density of SMCs and macrophage/foam cells within the neointima was calculated by dividing the number of cells by the area of the plaque. Total cholesterol, triglyceride, high density lipoprotein, and low density lipoprotein were significantly increased compared with levels before the initiation of a high-cholesterol diet, but there were no significant differences between the MMF-treated and untreated groups. Neointimal area in aortic tissue sections of the MMF-treated group (0.586 +/- 0.602 mm(2)) was significantly lower when compared with that in control animals (1.082 +/- 0.621 mm(2)) (P < 0.05). The densities of neointimal SMCs and monocytes/macrophages in the control group were 778 +/- 293 and 341 +/- 90 cells/mm(2), respectively. MMF treatment significantly reduced the number of neointimal SMCs (506 +/- 185 cells/mm(2)) (P < 0.05). The number of monocytes/macrophages was also reduced after MMF treatment (260 +/- 124 cells/mm(2)) but not significantly. Our results demonstrate that the administration of MMF significantly reduced neointimal SMC accumulation and plaque development in a hypercholesterolemic model of atherosclerosis. |
| Mycophenolate mofetil treatment reduces cholesterol-induced atherosclerosis in the rabbit Romero, F., B. Rodriguez-Iturbe, et al. (2000), Atherosclerosis 152(1): 127-33. Abstract: Immunosuppressive therapy has been shown to either improve or, more frequently, enhance the development of atherosclerosis. We tested the effect of mycophenolate mofetil (MMF), an inhibitor of nucleotide synthesis widely used in transplant therapy, in diet-induced atherosclerosis in the rabbit. Two groups (n=10 each) of New Zealand White (NZW) rabbits were fed a 1% cholesterol diet for 12 weeks. One group received MMF (CHOL+MMF group) by gastric gavage (30 mg/kg daily) and the other group (CHOL) received the same volume of saline by the same route. There were no differences in the serum cholesterol (mean values > or =30 mmol/l in both groups after 2 weeks) or in the triglyceride, blood sugar, total protein, and albumin serum levels and weight gain in both groups of animals. The cholesterol-fed untreated rabbits had atherosclerotic plaques covering 43.9.1+/-SD 16.40% of their thoracic aorta and 41.9+/-22. 59% of their abdominal aorta, while the MMF treated group had 18. 5+/-7.17% and 17.7+/-9.71%, respectively (P<0.01). The cholesterol content of the aorta (mg/g) in the cholesterol-fed untreated group was 4.61+/-SD 1.21 in the thoracic aorta and 4.54+/-2.07 in the abdominal aorta, whereas the MMF treated group had and 2.83+/-0.84 and 2.77+/-1.44, respectively (P<0.01). Infiltrating macrophages (RAM 11 positive cells/100 nuclei) in the intimal layer of the aorta were 58.4+/-SD26.16 in the CHOL group and 8.5+/-5.51 in the CHOL+MMF group: (P<0.001). CD18 positive cells/100 nuclei were 27.4+/-17.6 in the CHOL group and 5.3+/-3.82 in the CHOL+MMF group (P<0.01), and the intima/media ratio was 0.66+/-0.11 in the CHOL group and 0. 30+/-0.09 in the MMF treated rabbits (P<0.001). MMF also reduced proliferating smooth muscle cells (HHF35 positive) infiltrating between the macrophages. These results indicate that MMF ameliorates importantly the atherogenic potential of a high cholesterol diet and this effect is associated with a reduction in macrophage and foam cell infiltration and smooth muscle cell proliferation and infiltration. Since chronic treatment with this drug is given routinely in various clinical conditions with relatively minor side effects, consideration may be given to its use as adjuvant therapy in atherosclerotic cardiovascular disease. |
| Myelin glycosphingolipid/cholesterol-enriched microdomains selectively sequester the non-compact myelin proteins CNP and MOG Kim, T. and S. E. Pfeiffer (1999), J Neurocytol 28(4-5): 281-93. Abstract: Plasma membranes are complex arrays of protein and lipid subdomains. Detergent-insoluble, glycosphingolipid/cholesterol-enriched micro-domains (DIGCEMs) have been implicated in protein sorting and/or as sites for signaling cascades in the plasma membrane. We previously identified the presence of DIGCEMs in oligodendrocytes in culture and purified myelin and characterized a novel DIGCEM-associated tetraspan protein, MVP17/rMAL (Kim et al. (1995) Journal of Neuroscience Research 42, 413-422). We have now analyzed the association of known myelin proteins with DIGCEMs in order to provide a better understanding of their roles during myelin biogenesis. We used four well-established criteria to identify myelin DIGCEM-associated proteins: insolubility in a non-ionic detergent Triton X-100 at low temperature (4 degrees C), flotation of the insoluble complexes to low density fractions in sucrose gradients, and TX-100 solubilization at 37 degrees C, or at 4 degrees C following treatment with the cholesterol-binding detergent saponin. We demonstrate that these proteins fall into four distinct groups. Although all tested proteins could be floated to a low-density fraction, proteolipid protein (PLP), myelin basic protein (MBP) and myelin associated glycoprotein (MAG) were solubilized by the detergent extraction, and connexin32 (Cx32) and oligodendrocyte-specific protein (OSP) met only some of the criteria for DIGCEMs. Only the non-compact myelin proteins 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) and myelin/oligodendrocyte glycoprotein (MOG) satisfied all four criteria for DIGCEM-associated proteins. Significantly, only approximately 40% of CNP and MOG were selectively associated with DIGCEMs. This suggests that they may have both non-active "soluble", and functionally active DIGCEM-associated, forms in the membrane, consistent with current views that DIGCEMs provide platforms for bringing together and activating components of the signal transduction apparatus. We therefore propose that CNP and MOG may have unique roles among the major myelin proteins in signaling pathways mediated by lipid-protein microdomains formed in myelin. |
| Myeloperoxidase interaction with mixed monolayers of lecithin and cholesterol Chasovnikova, L. V., V. E. Formaziuk, et al. (1991), Biull Eksp Biol Med 111(2): 146-8. Abstract: Interaction between myeloperoxidase and mixtures of lecithin-cholesterol monolayers were investigated. Solubility of the enzyme in 1-octanol or in octanol were tested too. It is shown that myeloperoxidase demonstrates an ability to concentrate on phase limits. The enzyme well dissolves in lipid membrane phases. It is possible to assume that myeloperoxidase penetrates and accumulates in the eye lens. |
| Myocardial infarction in young adults with low-density lipoprotein cholesterol levels < or = 100 mg/dL: clinical profile and 1-year outcomes Akosah, K. O., R. M. Cerniglia, et al. (2001), Chest 120(6): 1953-8. Abstract: STUDY OBJECTIVES: To define the clinical profile of young adults with optimal low-density lipoprotein (LDL) cholesterol levels who present with acute myocardial infarctions (MIs); to compare and contrast differences in the clinical profiles of young adults admitted to the hospital with MIs who have LDL cholesterol levels < or = 100 mg/dL and those with LDL cholesterol values > or = 160 mg/dL; and to evaluate the clinical outcomes for the two groups at 1 year. DESIGN: A retrospective chart review was conducted on all young men (55 years) and women (65 years) admitted to the hospital for MIs within a 2-year period (n = 232). A history of cardiovascular risk factors and 1-year outcomes were obtained. SETTING: Rural community medical center serving a tri-state area in the midwestern United States. PATIENTS: Patients were included in this analysis if (1) a lipid profile was drawn within 24 h of hospital admission and (2) the patient was not receiving a statin medication on hospital admission. MEASUREMENTS AND RESULTS: Of the 183 patients who met the inclusion criteria, as many as 68% (124 patients) had LDL cholesterol levels of < or = 130 mg/dL, 29% (53 patients) had LDL cholesterol level of < or = 100 mg/dL, and only 14% (26 patients) had LDL cholesterol levels of > or = 160 mg/dL. Patients were categorized into group 1 if their LDL cholesterol level was < or = 100 mg/dL and were categorized into group 2 if their LDL cholesterol level was > or = 160 mg/dL. In group 2, 92% of patients were placed on a statin medication. By 1 year, the mean LDL cholesterol level had decreased from 188 to 106 mg/dL. The rate of coronary artery bypass graft and percutaneous coronary intervention procedures was similar between groups. Hospital readmission rates (43.4% vs 50%, respectively) and 1-year mortality rates (9% vs 8%, respectively) were not different between groups group 1 and 2. CONCLUSIONS: Young adults experiencing acute MIs typically have acceptable cholesterol levels (ie, < or = 130 mg/dL) or optimal values (ie, < or = 100 mg/dL). In those patients with abnormal cholesterol levels, a combined strategy of aggressive intervention and adherence to secondary prevention protocols including lipid control is successful in improving outcomes. |
| Myocardial membrane cholesterol: effects of ischaemia Venter, H., S. Genade, et al. (1991), J Mol Cell Cardiol 23(11): 1271-86. Abstract: Evidence has recently been presented that myocardial ischaemia is associated with a significant increased mitochondrial cholesterol content, suggesting a redistribution of cholesterol within the ischaemic cell (Rouslin et al. 1980, 1982). The aim of this study was therefore to determine the effects of different periods of ischaemia and reperfusion on the cholesterol content of myocardial mitochondria, sarcoplasmic reticulum and sarcolemma. Using the isolated perfused rat heart as experimental model, it was demonstrated that increasing periods of ischaemia (15-60 min) caused a progressive loss of cholesterol from the tissue as well as from the sarcolemma and sarcoplasmic reticulum, concomitant with a significant increase in mitochondrial cholesterol content. These compositional changes were associated with a marked increase in sarcolemmal and mitochondrial microviscosity, while that of the sarcoplasmic reticulum was reduced. To gain more insight into the mechanisms controlling intracellular cholesterol distribution, control and ischaemic hearts were perfused with either exogenous cholesterol or its precursor U-14Cacetate as an indicator of endogenous cholesterol synthesis. Perfusion with exogenous cholesterol resulted in significant increases in the membrane cholesterol content of control hearts. However, hypoxic, low flow perfusion prevented cholesterol enrichment of the sarcolemmal and sarcoplasmic reticulum membranes, while the cholesterol content of the mitochondria was increased from 99.48 +/- 12.75 to 127.61 +/- 1.84 nmols/mg protein, indicating specific incorporation into this membrane system. Incorporation of U-14Cacetate into cholesterol in the sarcoplasmic reticulum was increased by 120% in ischaemic conditions. However, a marked redistribution of newly synthesized cholesterol was observed within the ischaemic cell: under control conditions most of the labelled cholesterol was transferred to the sarcolemma and least to the mitochondria, while this distribution pattern was reversed in ischaemia. In view of the fact that exchange of cholesterol between membranes is affected by both phospholipid polar head-group composition and acyl chain length and saturation, it is suggested that prior ischaemia-induced membrane compositional changes might lead to intracellular cholesterol redistribution. Finally, to determine whether cholesterol loss affects sarcolemmal permeability, hearts enriched in sarcolemmal cholesterol were subjected to 15 or 30 min global ischaemia followed by reperfusion and the rate of enzyme release determined. However, enzyme release was similar in treated and untreated hearts, indicating that sarcolemmal cholesterol loss probably does not affect its permeability. |
| Myocardial perfusion after cholesterol lowering Gould, K. L. (1996), J Atheroscler Thromb 3(2): 59-61. |
| Myristic acid-rich fat raises plasma LDL by stimulating LDL production without affecting fractional clearance in gerbils fed a cholesterol-free diet Hajri, T., P. Khosla, et al. (1998), J Nutr 128(3): 477-84. Abstract: The imbalance that develops between low-density lipoprotein (LDL) production and clearance during saturated fat consumption is responsible for expanding the circulating LDL pool. To assess the imbalance attributable to fatty acids alone, i.e., without the interaction of dietary cholesterol, the most fat-sensitive species available (the gerbil) was challenged with either a 12:0+14:0 rich-fat (high coconut, low safflower) or high 18:2 (high safflower, low coconut) fat for 4-5 wks. The plasma lipoprotein cholesterol profile, including lipoprotein composition, particle size and 125I-LDL turnover were measured. Although total plasma cholesterol (TC) was threefold higher with saturated fatty acid (SFA) feeding (230 vs. 70 mg/100 mL; 5.9 +/- 0.1 vs. 1.8 +/- 0.05 mmol/L, P < 0. 0001) and LDL cholesterol (LDL-C) was fivefold greater (10 vs. 54 mg/100 mL; 0.26 +/- 0.02 vs. 1.4 +/- 0.02 mmol/L, P < 0.001), the high-density lipoprotein (HDL2) fraction increased the most (27 vs. 79 mg/100 mL; 0.7 +/- 0.02 vs. 2.0 +/- 0.1 mmol/L, P < 0.05) with minimal HDL3 (NS) difference (16 vs. 26 mg/100 mL; 0.43 +/- 0.08 vs. 0. 7 +/- 0.05 mmol/L). Particle composition and size did not differ between groups. LDL kinetic analyses revealed that the fractional catabolic rate did not differ between gerbils with these extreme fat intakes, implicating overproduction and not reduced clearance as the primary consideration in LDL expansion. Thus SFA-induced cholesterolemia can be severe in the absence of dietary cholesterol with a greater impact on high-density lipoprotein than LDL and without an appreciable role attributed to LDL clearance (receptors). |
| Myth about the disadvantage of decreasing serum cholesterol refuted Erkelens, D. W. (1993), Ned Tijdschr Geneeskd 137(19): 944-8. |
| Myth about the disadvantage of lowering of serum cholesterol level refuted Duits, N. (1993), Ned Tijdschr Geneeskd 137(28): 1419-21. |