| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| The acute effect of 30 min of moderate exercise on high density lipoprotein cholesterol in untrained middle-aged men Hubinger, L. M. and L. T. Mackinnon (1992), Eur J Appl Physiol Occup Physiol 65(6): 555-60. Abstract: Fifteen middle-aged, untrained (defined as no regular exercise) men (mean age 49.9 years, range 42-67) cycled on a cycle ergometer at 50 rpm for 30 min at an intensity producing 60% predicted maximum heart rate (fc,max), where fc,max = 220 - age. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (Tg) concentrations were measured from fasting fingertip capillary blood samples collected at rest, after 15 and 30 min of exercise, and at 15 min post-exercise. The mean HDL-C level increased significantly from the resting level of 0.85 mmol.l-1 to 0.97 mmol.l-1 (P < 0.05) after 15 min of exercise, increased further to 1.08 mmol.l-1 (P < 0.01) after 30 min of exercise and remained elevated at 1.07 mmol.l-1 (P < 0.01) at 15 min post-exercise. These increases represented changes above the mean resting level of 14.1%, 27.1% and 25.9% respectively. The HDL-C/LDL-C ratio increased significantly from a resting ratio of 0.20 to 0.26 after 30 min of exercise (P < 0.01) and to 0.24 at 15 min post-exercise (P < 0.05). The mean Tg level increased significantly from a resting level of 0.88 mmol.l-1 to 1.05 mmol.l-1 after 15 min, and to 1.06 mmol.l-1 after 30 min of exercise (P < 0.05 at each time). The TC/HDL-C ratio decreased significantly (P = 0.05) after 30 min of exercise and at 15 min post-exercise by 18.8% and 14%, respectively. No significant changes were observed in the levels of TC or LDL-C over time.(ABSTRACT TRUNCATED AT 250 WORDS) |
| The adult patient with a congenital GH deficiency. Cholesterol-lowering effects of therapy with biosynthetic GH Sartorio, A., A. Conti, et al. (1994), Minerva Endocrinol 19(1): 13-8. Abstract: In adults with childhood onset GH deficiency, serum total and LDL cholesterol levels were significantly higher (p < 0.05 and < 0.01, respectively), while serum HDL cholesterol levels were significantly lower (p < 0.05) than those recorded in an age and sex matched control group. These biochemical alterations determined the presence of a marked increase of coronary risk indexes (total/HDL cholesterol and LDL/HDL cholesterol) which were significantly higher (p < 0.0001) than in controls. Serum VLDL and triglycerides levels were similar to those found in controls. After recombinant GH treatment (0.5 IU/kg/week, sc), serum total and LDL cholesterol levels were significantly reduced, becoming similar to those recorded in controls after six months' therapy. Serum HDL cholesterol levels, which were slightly reduced after 3 months, significantly increased after 6 months of GH treatment, becoming similar to those recorded in controls; no significant modifications were observed in VLDL cholesterol and triglycerides levels during treatment. The coronary risk indexes fell during GH treatment, but still remained higher than in controls. On the basis of these promising data, it is tempting to speculate that more prolonged GH treatment might be able to ameliorate the risk for cardiovascular diseases in adults with GH deficiency. Although further additional studies with a larger number of patients are needed to confirm these preliminary observations, adults with GH deficiency should be recommended to take into great consideration the control of other risk factors involved in the genesis of coronary disease. |
| The advisability of implementing cholesterol screening in school-age children and adolescents with a family history of cardiovascular disease and hyperlipidaemia Liu, C. S., C. C. Lin, et al. (1999), Fam Pract 16(5): 501-5. Abstract: BACKGROUND: The family basis of coronary heart disease is well recognized and it is important for family physicians to assess whether children have elevated cholesterol levels. OBJECTIVES: We aimed to evaluate the advisability of implementing cholesterol screening in children with a family history of cardiovascular disease and hyperlipidaemia. METHODS: We conducted a cross-sectional study in Taiwan from February to June 1996. There were 47,800 students in the population. A total of 4520 students were recruited by two-stage sampling. All the participants were required to fill out a structured questionnaire. RESULTS: The response rate was 92.5%. Our results show that 16-18% of the children had a positive family history of cardiovascular disease or hyperlipidaemia. Children with a family history of hyperlipidaemia were significantly more likely to have elevated total cholesterol and low-density lipoprotein cholesterol than those without such a history (both odds ratios: 1.4, P < 0.05). Positive predictive values of hyperlipidaemia were less than 13% based on family history. More than 75% of children with abnormal lipid levels would be missed. CONCLUSIONS: The data suggest that parents' self-reported family history is an ineffective means of identifying children with elevated serum lipid levels in Taiwan. Further research and modification of current National Cholesterol Education Program Panel guidelines for selective cholesterol screening in children may be warranted. |
| The age-related rise of plasma cholesterol in humans is not caused by a cell removal defect of LDL particles: 'in vitro' studies in peripheral mononuclear blood cells Neves, M. Q., M. D. Carvalho, et al. (1997), Gerontology 43(4): 232-41. Abstract: In healthy subjects with a normal body mass index, total plasma cholesterol, low-density lipoprotein (LDL) cholesterol, and apoB lipoprotein levels are higher in older individuals (n = 34) than in younger subjects (n = 43). The two groups studied ranged in age from 60 to 93 years and from 17 to 30 years, respectively. The cholesterol synthesis rates of peripheral mononuclear blood cells from 14C-acetate, total and unesterified cholesterol concentrations in freshly isolated cells, and the rates of uptake of pooled donor LDL, labeled with 125I- or 14C-cholesteryl oleoyl ether, by cells derepressed in a lipoprotein-free medium were similar in both experimental groups. Thus, the rise of LDL cholesterol with age would seem to be likely secondary to the higher rate of very-low-density lipoprotein production, as shown by other investigators. |
| The almost forgotten biological potentials of cholesterol and its intermediates: cholesterol reduction and myositis Twickler, M., J. D. Banga, et al. (2003), Cardiovasc Drugs Ther 17(5-6): 395-6. |
| The American College of Physicians guidelines for screening blood cholesterol levels: a commentary Criqui, M. H., B. Kinosian, et al. (1998), Am J Med 105(1A): 75S-76S. |
| The Amerindian epidemics of cholesterol gallstones: the North and South connection Nervi, F., J. F. Miquel, et al. (2003), Hepatology 37(4): 947-8; author reply 948-9. |
| The amount of cholesterol relative to apolipoprotein B in low-density lipoproteins relates primarily to high-density lipoprotein cholesterol in children: the Bogalusa Heart Study Srinivasan, S. R., W. Bao, et al. (1994), Metabolism 43(8): 1042-6. Abstract: Serum low-density lipoprotein (LDL) particles vary in size, composition, and atherogenic potential. Relationships between the ratio of cholesterol to apolipoprotein B (apo B) within LDL, and levels of other lipoprotein variables in serum were examined in a biracial (black-white) sample (N = 2,053) of 8- to 17-year-olds whose median triglyceride level remained relatively low (56 mg/dL). The LDL cholesterol to apo B ratio showed a significant positive association with high-density lipoprotein (HDL) cholesterol (r =.36 to.44), HDL2 cholesterol (r =.34 to.50), HDL3 cholesterol (in whites only, r =.24 to.28), and apo A-I (r =.17 to.27), and a significant inverse association with triglycerides (except in black girls, r = -.15 to -.19). The best predictor of the LDL cholesterol to apo B ratio was HDL cholesterol or HDL2 cholesterol in all four race-gender groups; triglycerides entered as a predictor variable only in black boys. Since relationships of LDL and HDL to coronary heart disease (CHD) risk are considered interdependent, a subgroup of children with apo B-enriched LDL and low HDL cholesterol may be potentially at increased risk. |
| The amount of dietary cholesterol changes the mode of effects of (n-3) polyunsaturated fatty acid on lipoprotein cholesterol in hamsters Lin, M. H., S. C. Lu, et al. (2004), Ann Nutr Metab 48(5): 321-8. Abstract: This study was designed to investigate the effects of the interaction between dietary (n-3) polyunsaturated fatty acids (PUFA) and different dietary cholesterol content on plasma and liver cholesterol in hamsters. Male Syrian hamsters consumed diets containing an incremental increase in dietary cholesterol content (0, 0.025, 0.05, 0.1 and 0.2%, w/w) with either (n-3) PUFA (21 g/100 g fatty acids) or (n-6) PUFA (37.4 g/100 g fatty acids) fat for 6 weeks. In hamsters fed the nonatherogenic diet (0 or 0.025% dietary cholesterol), very low density lipoprotein (VLDL)-cholesterol levels in the (n-3) PUFA group were not significantly different from those in the (n-6) PUFA group, and low density lipoprotein (LDL)-cholesterol levels in the (n-3) PUFA group were significantly lower than those in the (n-6) PUFA group. In contrast, in hamsters fed the atherogenic diet (0.1 or 0.2% dietary cholesterol), VLDL- and LDL-cholesterol levels in the (n-3) PUFA group were significantly higher than those in the (n-6) PUFA group, in a dose-dependent manner. When the hamsters were fed with 0, 0.025, 0.05, 0.1 or 0.2% (w/w) dietary cholesterol, high density lipoprotein (HDL) cholesterol concentration was significantly lower in the (n-3) PUFA group than those in the (n-6) PUFA group. Hepatic cholesteryl esters were significantly lower, while hepatic microsomal acyl-coenzyme A:cholesterol acyltransferase activity and VLDL-cholesteryl esters were significantly higher in hamsters fed (n-3) PUFA with the atherogenic diet (0.1 or 0.2% dietary cholesterol) than in those fed (n-6) PUFA with the atherogenic diet. Our results demonstrate that the amount of dietary cholesterol is an important factor in determining the mode and extent of effects of dietary (n-3) PUFA, especially on VLDL- and LDL-cholesterol levels. When dietary cholesterol intake was above 0.1% (w/w), the plasma cholesterol-lowering effect of (n-3) PUFA disappeared, and instead, it showed a cholesterol-increasing effect. However, the effects of dietary (n-3) PUFA on HDL-cholesterol are independent of dietary cholesterol content. |
| The ansamycins: hypolipidemic agents stimulating cholesterol removal by nonclassical mechanisms Gibson, J. C., W. H. Lee, et al. (1994), J Lipid Res 35(9): 1524-34. Abstract: The ansamycins CGP 43371 and CGS 24565 are derivatives of the antibiotic rifamycin that reduce plasma cholesterol levels in both primate and nonprimate species. In vivo, a striking accumulation of macrophage cholesteryl ester was seen in ansamycin-treated rats and hamsters, but carbon clearance studies and reticuloendothelial system blockade by gadolinium chloride indicated that phagocytosis was not involved. Simple addition of an ansamycin to macrophages or monocytes in vitro failed to stimulate radiolabeled lipoprotein cholesteryl ester association or mass accumulation. In contrast to mononuclear cells, however, the ansamycins did enhance radiolabeled lipoprotein cholesteryl ester association by liver cells in vitro. Primary hepatocyte cultures prepared from rats treated with radiolabeled CGP 43371 secreted CGP 43371 over an 18-h period in a fraction floating at d < 1.02 g/ml after density gradient ultracentrifugation that was relatively enriched in apoA-I. The medium containing this secreted 14CGP 43371-labeled lipoprotein was capable of enhancing the cholesteryl ester content of macrophages in vitro, suggesting that ansamycin-induced liver modification of lipoproteins might be involved. These drugs may serve as valuable tools for studying mechanisms of lipoprotein uptake. |
| The antiatherogenic effect of nifedipine on intramural small coronary arterial lesions in cholesterol-fed rabbits Kato, H., R. Okada, et al. (1998), Angiology 49(1): 49-54. Abstract: The objective of this study was to examine the suppressive effect of nifedipine on intramural coronary arterial lesions in cholesterol-fed rabbits. Each rabbit in Groups A (n=6) and B (n=5) was fed a 0.3% cholesterol diet and was orally administered nifedipine (40 mg/day) or placebo. Each rabbit in Groups C (n=5) and D (n=6) was fed a 0.5% cholesterol diet and was orally administered nifedipine (40 mg/day) or placebo. The serum concentrations of total cholesterol (TC) were determined at 1-week intervals to calculate the integrated values. The lesion induction ratio was defined as the ratio of intramural coronary arteries 50-150 microm in diameter with arterial lipoidosis to the total number of arteries of the same diameter. There were no significant differences between the nifedipine-treated and placebo groups in either the integrated TC or lesion induction ratio in either the 0.3% and 0.5% cholesterol-fed rabbits. This study demonstrates that nifedipine does not suppress atherogenesis in the intramural small coronary arteries of cholesterol-fed rabbits. |
| The antiatherogenic role of high-density lipoprotein cholesterol Kwiterovich, P. O., Jr. (1998), Am J Cardiol 82(9A): 13Q-21Q. Abstract: Landmark clinical studies in the past 5 years that demonstrated diminished mortality and first coronary events following lowering of low-density lipoprotein (LDL) cholesterol stimulated considerable interest in the medical community. Yet, high-density lipoprotein (HDL) cholesterol, which transports circulating cholesterol to the liver for clearance, clearly also exerts antiatherogenic effects. The Framingham Heart Study produced compelling epidemiologic evidence indicating that a low level of HDL cholesterol was an independent predictor of coronary artery disease (CAD). Emerging experimental and clinical findings are, collectively, now furnishing a solid scientific foundation for this relation. First, the reverse cholesterol transport pathway--including the roles of nascent (pre-beta) HDL, apolipoprotein A-I, lecithin-cholesterol acyltransferase (LCAT), cholesteryl ester transport protein, and hepatic uptake of cholesteryl ester from HDL by liver--is better understood. For example, the identification of a hepatic HDL receptor, SR-BI, suggests a mechanism of delivery of cholesteryl ester to liver that differs from the receptor-mediated uptake of LDL. Second, apolipoprotein A-I, the major protein component of HDL, and 2 enzymes on HDL, paraoxonase and platelet-activating factor acetylhydrolase appear to diminish the formation of the highly atherogenic oxidized LDL. Third, lower levels of HDL cholesterol are associated in a dose-response fashion with the severity and number of angiographically documented atherosclerotic coronary arteries. Fourth, low HDL cholesterol predicts total mortality in patients with CAD and desirable total cholesterol levels (<200 mg/dL). Fifth, low HDL cholesterol concentrations appear to be associated with increased rates of restenosis after percutaneous transluminal coronary angioplasty. In terms of elevating HDL cholesterol, cessation of cigarette smoking, reduction to ideal body weight, and regular aerobic exercise all appear important. Most medications used to treat dyslipidemias will raise HDL cholesterol levels modestly; however, niacin appears to have the greatest potential to do so, and can increase HDL cholesterol up to 30%. Recognizing these data, the most recent report of the National Cholesterol Education Program identified low HDL cholesterol as a CAD risk factor and recommended that all healthy adults be screened for both total cholesterol and HDL cholesterol levels. |
| The antihypertensive drug propranolol enhances LDL catabolism and alters cholesterol metabolism in human cultured fibroblasts Maziere, C., J. C. Maziere, et al. (1990), Atherosclerosis 81(2): 151-60. Abstract: The effects of 3 beta-blockers with different pharmacological properties (non-selective: propranolol; beta 1-selective: metoprolol; and with intrinsic sympathomimetic activity: pindolol) were comparatively studied on LDL and lipid metabolism in human fibroblasts. At 10(-4) M, propranolol increased low density lipoprotein binding, uptake and degradation by 1.5-, 2.2- and 1.8-fold, respectively, whereas metoprolol and pindolol had no effect. This effect of propranolol is mainly due to an increase in LDL receptor number. Propranolol also enhanced sterol, triacylglycerol, fatty acid and phospholipid synthesis by 2-3-fold from sodium acetate. Cholesterol esterification by oleic acid was significantly and specifically decreased 4-fold by propranolol. Metoprolol and pindolol affect neither sterol synthesis nor cholesterol esterification. Pretreatment of cultured fibroblasts with propranolol induced an increase in hydroxymethyl-glutaryl-coenzyme A reductase activity and a decrease in acyl-coenzyme A: cholesterol-O-acyltransferase (ACAT) activity. Propranolol inhibited the induction of ACAT activity by exogenous cholesterol. Preincubation of a cell-free extract with propranolol also induced inhibition of ACAT activity. Propranolol decreased the cholesteryl ester content of cultured cells. These effects of propranolol on LDL and cholesterol metabolism might be related to the amphiphilic properties of the drug and suggest an effect on the cholesterol intracellular traffic. The decrease in cholesterol esterification and in the cholesteryl ester cellular level induced by propranolol may be involved in its antagonizing effect on experimental atherogenesis. |
| The antioxidant action of ketoconazole and related azoles: comparison with tamoxifen and cholesterol Wiseman, H., C. Smith, et al. (1991), Chem Biol Interact 79(2): 229-43. Abstract: The azole antifungal drug ketoconazole was found to inhibit Fe(III)-ascorbate dependent lipid peroxidation using either rat liver microsomes or ox-brain phospholipid liposomes as the substrate. It also inhibited microsomal peroxidation induced by the Fe(III)-ADP/NADPH system. The related azoles, miconazole and clotrimazole, were much weaker inhibitors than ketoconazole. Ketoconazole was approximately equipotent with the triphenylethylene anticancer drug tamoxifen in the microsomal system and was almost as effective as 4-hydroxytamoxifen in the liposomal system. Ketoconazole introduced into phospholipid liposomes during their preparation inhibited Fe(III)-ascorbate induced lipid peroxidation to a greater extent than similarly introduced cholesterol, ergosterol or tamoxifen. Miconazole and clotrimazole were again poor inhibitors of lipid peroxidation in this system. These antioxidant effects of ketoconazole may be due to membrane stabilization in the systems used. The implications of our findings for the clinical applications of these drugs are discussed. |
| The antioxidant butylated hydroxytoluene prevents early cholesterol-induced microcirculatory changes in rabbits Xiu, R. J., A. Freyschuss, et al. (1994), J Clin Invest 93(6): 2732-7. Abstract: Microcirculation was studied during 10 wk in untreated rabbits (n = 13) and in rabbits treated with dietary addition of 1% cholesterol (n = 13), 1% cholesterol + 1% of the antioxidant BHT (butylated hydroxytoluene) (n = 11), or 1% BHT (n = 5). The studies were performed by direct intravital microscopic imaging of the left and right conjunctivae with the use of a stereo microscope and a high resolution television camera. Microvessel diameter, erythrocyte flow velocity, and microhemorheologic conditions were evaluated quantitatively via a computer-assisted digital image processing system. Significant and marked changes occurred in all the above variables as a consequence of cholesterol feeding. After 3 wk of feeding there was a dramatic decrease (approximately 30%) in blood flow velocity in arterioli of the third order (P < 0.0001), accompanied by aggregation of cells in 40-50% of the smaller conjunctival vessels (P < 0.0001). These changes were enhanced further during the following 7 wk of treatment. All the above changes in the microcirculation were markedly reduced by the addition of BHT treatment. The diameter of the above arterioli decreased in the purely cholesterol-fed group (P < 0.005), whereas this did not occur in the group fed both cholesterol and BHT. In rabbits fed BHT in the absence of cholesterol, there was no significant effect on any assessed microcirculatory variable. In conclusion, the results demonstrate that the antioxidant BHT prevented early cholesterol-induced microcirculatory changes. This prevention occurred in the absence of a reduction of blood lipid levels. The results provide strong support for the hypothesis that a considerable part of the effects on microcirculation in hypercholesterolemia may be due to cholesterol-induced oxidations and not to cholesterol itself. The results are discussed in relation to the previously demonstrated antiatherogenic effect of BHT and the possible use of antioxidants in the therapy and prophylaxis of atherosclerosis. |
| The apoB/apoA-I ratio is better than the cholesterol ratios to estimate the balance between plasma proatherogenic and antiatherogenic lipoproteins and to predict coronary risk Walldius, G., I. Jungner, et al. (2004), Clin Chem Lab Med 42(12): 1355-63. Abstract: BACKGROUND: The apolipoprotein B (apoB)/apoA-I ratio represents the balance of proatherogenic and antiatherogenic lipoproteins. The purpose of this study was to determine whether the apoB/apoA-I ratio was superior to any of the cholesterol ratios - total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C), low-density lipoprotein cholesterol (LDL-C)/HDL-C and non-HDL-C/HDL-C - in predicting the risk of coronary disease. Moreover, we examined whether any lipids, lipoproteins or cholesterol ratios add significant predictive information beyond that provided by the apoB/apoA-I ratio. METHODS: Plasma lipids, lipoproteins, apoB, and apoA-I were measured in 69,030 men and 57,168 women above 40 years of age. After a mean follow-up of 98 months, 1183 men and 560 women had died from a myocardial infarction in this prospective apolipoprotein-related mortality risk (AMORIS) study. RESULTS: High apoB and a high apoB/apoA-I ratio were strongly related to increased coronary risk, while high apoA-I was inversely related to risk. The apoB/apoA-I ratio was superior to any of the cholesterol ratios in predicting risk. This advantage was most pronounced in subjects with LDL-C levels <3.6 mmol/l. Addition of lipids, lipoproteins or any cholesterol ratio to apoB/apoA-I in risk models did not further improve the strong predictive value of apoB/apoA-I. CONCLUSIONS: These results indicate that the apoB/apoA-I ratio is at present the best single lipoprotein-related variable to quantitate coronary risk. Given the additional advantages apolipoproteins possess - fasting samples are not required, apoB/apoA-I is a better index of the adequacy of statin therapy than LDL-C, and the measurement of apoB and apoA-I are standardized, whereas LDL-C and HDL-C are not - there would appear to be considerable advantage to integrating apolipoproteins into clinical practice. |
| The apolipoprotein E gene and the serum low-density lipoprotein cholesterol response to dietary fiber Jenkins, D. J., R. A. Hegele, et al. (1993), Metabolism 42(5): 585-93. Abstract: Our goal was to determine whether differences in apolipoprotein E (apo E) influenced the response to dietary changes aimed at reducing serum cholesterol levels, especially increases in fiber. Apo E phenotype and genotype were determined in 43 men and 24 women who had previously taken part in parallel 2-week metabolic dietary studies involving either wheat bran or oat bran supplementation at a level of 6.8 g fiber/1,000 kcal. Fasting blood lipid measurements had been made at the beginning and end of the 2-week metabolic period. Reductions in low-density lipoprotein (LDL) cholesterol levels across both oat and wheat bran diets were significantly different depending on the E allele (P =.048). The LDL cholesterol level reduction for E2 carriers (0.60 +/- 0.14 mmol/L, n = 13) was greater than that for E3 homozygotes (0.21 +/- 0.07 mmol/L, n = 38; P =.014) and E4 carriers (0.28 +/- 0.12 mmol/L, n = 16; P =.09). Only the change in dietary fiber on the oat bran diet was related significantly to the decrease in LDL cholesterol levels (r = -.47, P =.007; n = 32). No such relationship was seen on the wheat bran diet (r = -.010, P =.59; n = 33). Carriers of the E2 allele appear to be more responsive than noncarriers to a dietary change involving increased fiber intake. The data also support a lipid-lowering advantage of oat bran over wheat bran. Current dietary recommendations to reduce serum lipid levels may vary in effectiveness depending on distribution of apo E alleles in the different populations studied. |
| The apolipoprotein E phenotype has a strong influence on tracking of serum cholesterol and lipoprotein levels in children: a follow-up study from birth to the age of 11 years Kallio, M. J., L. Salmenpera, et al. (1998), Pediatr Res 43(3): 381-5. Abstract: The extent to which an individual maintains his position relative to the rest of the population is called tracking. The objective of this study was to examine the effect of the apolipoprotein E (apoE) phenotype on the tracking of serum cholesterol and lipoproteins from birth to the age of 11 y. In a longitudinal follow-up study of healthy children, concentrations of total serum cholesterol and triglyceride were determined at birth (n = 193), and at the ages of 2 (n = 192), 4 (n = 192), 6 (n = 190), 9 (n = 188), and 12 mo (n = 196), and 5 (n = 162) and 11 y (n = 153). Concentrations of total HDL, HDL2, and HDL3, VLDL, and LDL cholesterol were determined at 2, 6, 9, and 12 mo (n = 36), and 5 (n = 162) and 11 y (n = 153). The apoE phenotype was determined in 151 children. The children had the following apoE phenotypes: 4 had type 4/4 and 40 type 3/4 (group apoE4), 94 had type 3/3 (group apoE3), and 11 had type 2/3 and 2 type 2/4 (group apoE2). The correlation coefficients for total cholesterol levels during childhood compared with the level at 11 y of age were: 0.03 at birth, 0.26 (p < 0.001) at 2 mo, 0.24 (p < 0.001) at 4 mo, 0.24 (p < 0.001) at 6 mo, 0.28 (p < 0.001) at 9 mo, 0.41 (p < 0.001) at 12 mo, and 0.60 (p < 0.001) at 5 y. When the children were divided into three groups according to their apoE phenotypes, these three groups had the following correlation coefficients at 4 mo, 12 mo, or 5 y of age compared with the level at the age of 11 y; group apoE2: r = 0.65 (p < 0.01), r = 0.59 (p < 0.01), and r = 0.72 (p < 0.01); group apoE3: r = 0.27 (p < 0.01), 0.43 (p < 0.001), and r = 0.64 (p < 0.001); and group apoE4: r = 0.14 (p = NS), r = 0.33 (p < 0.05), and 0.42 (p < 0.01). The apoE phenotype also strongly influenced the tracking of the LDL cholesterol levels; the correlation coefficients between 5 and 11 y of age were for group apoE2 r = 0.84 (p < 0.001), for group apoE3 r = 0.70 (p < 0.001), and for group apoE4 r = 0.37 (p < 0.05). Our results indicate that the apoE phenotype strongly influences the tracking of lipids. The children having apoE 2/3, 2/4, and 3/3 phenotypes maintained their relative cholesterol and lipoprotein levels better than the others throughout the first 11 y of age. Because the apoE phenotype strongly affects the tracking of serum cholesterol, the usefulness of cholesterol screening in predicting future cholesterol values should be analyzed, keeping the apoE phenotype in mind. |
| The Arg123-Tyr166 central domain of human ApoAI is critical for lecithin:cholesterol acyltransferase-induced hyperalphalipoproteinemia and HDL remodeling in transgenic mice Holvoet, P., B. De Geest, et al. (2000), Arterioscler Thromb Vasc Biol 20(2): 459-66. Abstract: High density lipoprotein (HDL) metabolism and lecithin:cholesterol acyltransferase (LCAT)-induced HDL remodeling were investigated in transgenic mice expressing human apolipoprotein (apo) AI or an apoAI/apoAII chimera in which the Arg123-Tyr166 domain of apoAI was substituted with the Ser12-Ala75 domain of apoAII. Expression of apoAI and of the apoAI/apoAII chimera resulted in a respective 3. 5-fold and 2.9-fold increase of HDL cholesterol. Human LCAT gene transfer into apoAI-transgenic mice resulted in a 5.1-fold increase of endogenous LCAT activity. This increase was associated with a 2. 4-fold increase of the cholesterol ester-to-free cholesterol ratio of HDL, a shift from HDL(3) to HDL(2), and a 2.4-fold increase of HDL cholesterol levels. Agarose gel electrophoresis revealed that human LCAT gene transfer into human apoAI-transgenic mice resulted in an increase of pre-beta-HDL and of pre-alpha-HDL. In contrast, human LCAT gene transfer did not affect cholesterol levels and HDL distribution profile in mice expressing the apoAI/apoAII chimera. Mouse LCAT did not "see" a difference between wild-type and mutant human apoAI, whereas human LCAT did, thus localizing the species-specific interaction in the central domain of apoAI. In conclusion, the Arg123-Tyr166 central domain of apoAI is not critical for in vivo lipoprotein association. It is, however, critical for LCAT-induced hyperalphalipoproteinemia and HDL remodeling independent of the lipid-binding properties of apoAI. |
| The aromatase knockout mouse presents with a sexually dimorphic disruption to cholesterol homeostasis Hewitt, K. N., W. C. Boon, et al. (2003), Endocrinology 144(9): 3895-903. Abstract: The aromatase knockout (ArKO) mouse cannot synthesize endogenous estrogens due to disruption of the Cyp19 gene. We have shown previously, that ArKO mice present with age-progressive obesity and hepatic steatosis, and by 1 yr of age both male and female ArKO mice develop hypercholesterolemia. In this present study 10- to 12-wk-old ArKO mice were challenged for 90 d with high cholesterol diets. Our results show a sexually dimorphic response to estrogen deficiency in terms of cholesterol homeostasis in the liver. ArKO females presented with elevated serum cholesterol; conversely, ArKO males had elevated hepatic cholesterol levels. In response to dietary cholesterol, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase transcript levels were significantly reduced in females, whereas males showed more modest changes. Neither low density lipoprotein nor sterol regulatory element-binding protein expression levels were significantly altered by diet or genotype. The expression of Cyp7a, which encodes cholesterol 7 alpha-hydroxylase, was significantly reduced in ArKO females compared with wild-type females and was increased by cholesterol feeding. Cyp7a expression was significantly elevated in the wild-type males on the high cholesterol diet, although no difference was seen between genotypes on the control diet. The ATP-binding cassette G5 and ATP-binding cassette G8 transporters do not appear to be regulated by estrogen. The expression of acyl-coenzyme A:cholesterol acyltransferase 2 showed a sexually dimorphic response, where estrogen appeared to have a stimulatory effect in females, but not males. This study reveals a sexually dimorphic difference in mouse hepatic cholesterol homeostasis and roles for estrogen in the regulation of cholesterol uptake, biosynthesis, and catabolism in the female, but not in the male. |