| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Effects of added dietary lard on body weight and serum glucose and low density lipoprotein cholesterol in randombred broiler chickens Peebles, F. D., J. D. Cheaney, et al. (1997), Poult Sci 76(1): 29-36. Abstract: The effects of dietary lard on serum glucose (GLU) and lipids were determined in Athens-Canadian randombred broiler chickens. Birds were provided either 0, 3, or 7% added lard in nonisocaloric starter diets through 10 d of age (S1), followed by either 3 or 7% added dietary lard through 21 d of age (S2). A common grower diet was fed to all birds after 21 d. Body and organ weights, feed conversion, and concentrations of various blood constituents, including serum GLU and lipids, were determined weekly from 14 to 42 d of age. Constant levels of added fat in both S1 and S2 diets generally led to higher BW in males at 42 d. Relative testes weight at 14 d was higher in males fed 3% than in those fed 7% S2 diets, whereas 7% added lard in S2 diets preceded by no added fat in S1 diets resulted in higher relative spleen weights in males at 42 d. Serum GLU concentrations were highest in males that received 3% lard rather than no added lard in the S1 diet. Serum low density lipoprotein cholesterol (LDLC) concentrations at 14 d were highest in females fed constant levels of lard at either 3 or 7% in both starter periods. It was concluded that added lard fed to randombred chickens at various times and levels in starter diets elicited responses in organ weight and serum LDLC and GLU concentrations that varied with the sex and age of the bird and were not consistently related to BW. |
| Effects of added dietary taurine on erythrocyte lipids and oxidative stress in rabbits fed a high cholesterol diet Balkan, J., S. Oztezcan, et al. (2002), Biosci Biotechnol Biochem 66(12): 2701-5. Abstract: Lipid peroxidation leads to damage of polyunsaturated fatty acids of membrane phospholipids. The contribution of oxidative stress to hypercholesterolemia-induced hemolytic anemia and the effects of addition of taurine on erythrocyte lipid composition, oxidative stress, and hematological data were studied in rabbits fed on a high cholesterol (HC) diet (1%, w/w) for 2 months. The effects of taurine on erythrocyte hemolysis and H2O2-induced lipid peroxidation were investigated in normal rabbit erythrocytes in vitro. The HC diet resulted in increases in plasma lipids and lipid peroxide levels as well as increases in cholesterol levels and the cholesterol:phospholipid ratio in the erythrocytes. This diet caused a hemolytic anemia, but lipid peroxide levels remained unchanged in the erythrocytes of the rabbits. Taurine (2.5%, w/w) added to the food has an ameliorating effect on plasma lipids and lipid peroxide levels in rabbits fed on a HC diet. This treatment also caused decreases in elevated erythrocyte cholesterol levels and cholesterol:phospholipid ratio due to the HC diet, but it did not prevent the hemolytic anemia and did not change erythrocyte lipid peroxide levels. In addition, in an in vitro study, taurine did not protect erythrocytes against H2O2-induced hemolysis or lipid peroxidation. These results show that the HC diet causes hemolytic anemia without any changes in erythrocyte lipid peroxidation, and taurine treatment was not effective against hemolytic anemia caused by the HC diet. |
| Effects of age at menopause on serum cholesterol, body mass index, and blood pressure Akahoshi, M., M. Soda, et al. (2001), Atherosclerosis 156(1): 157-63. Abstract: Pre- and postmenopausal cholesterol (mg/dl), body mass index (BMI; kg/m(2)), and systolic blood pressure (SBP; mmHg) levels were compared in three age-at-time-of-menopause (ATM) groups to examine the relationship between the three risk factors and age ATM. Cholesterol, BMI, and SBP levels recorded 4 years prior to and 8 years after menopause were examined and increases in these risk factors between the two measurements were noted. The three age groups were: group A (n=49; age ATM 44+/-1<45), group B (n=395; 45< or =age ATM 48+/-1<50), and group C (n=578; age ATM 52+/-2> or =50). Cholesterol levels in premenopausal groups A (169+/-31 mg/dl, 40 years) and B (174+/-31, 44 years) were lower than those in group C (179+/-30, 48 years) (0.05< or =P<0.1 and P<0.05). Because, the increases in cholesterol were greater in group A (41+/-28 mg/dl) than in groups B (32+/-28) and C (29+/-28) (0.05< or =P<0.1 and P<0.05), cholesterol levels were identical among groups despite age differences upon reaching the postmenopause phase: group A (210+/-34, 51 years), group B (206+/-35, 56 years) and group C (208+/-35, 60 years). BMI and SBP increases were not different in groups A, B, and C. Differences in BMI and SBP levels among groups in order of premenopausal age were still observed after menopause. These data suggest that the greater increase in cholesterol associated with early menopause may be related to a higher prevalence of ischemic heart disease (IHD) in younger menopausal women. |
| Effects of age, gender, and menopausal status on plasma low density lipoprotein cholesterol and apolipoprotein B levels in the Framingham Offspring Study Schaefer, E. J., S. Lamon-Fava, et al. (1994), J Lipid Res 35(5): 779-92. Abstract: Plasma low density lipoprotein (LDL) cholesterol, non-high density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) B, the major protein constituent of LDL, were measured in 1,533 men (mean age 49 +/- 10 years) and 1,597 women (mean age 49 +/- 10 years) participating in the 3rd examination cycle of the Framingham Offspring Study. Mean plasma levels of LDL cholesterol and apoB were higher in men than in women (136 versus 132 mg/dl, P < 0.0001; and 109 versus 95 mg/dl, P < 0.0001, respectively). Increased age was associated with higher plasma LDL cholesterol and apoB levels, especially in women. After adjustment for age and body mass index, LDL cholesterol and apoB levels were still significantly higher in postmenopausal than in premenopausal women, indicating a hormonal effect on LDL metabolism. The associations between coronary heart disease (CHD) and LDL cholesterol, non-HDL cholesterol, apoB, and other plasma lipid and lipoprotein parameters were examined by dividing participants in four groups, based on approximate quartiles for these parameters. Elevated LDL cholesterol levels were not significantly associated with CHD in men, but were in women. This result, at variance with that of several longitudinal studies, is likely due to the cross-sectional design of our analysis. Elevated non-HDL cholesterol and apoB levels were significantly associated with the presence of CHD, in both males and females. A plasma apoB value > or = 125 mg/dl may be associated with an increased risk for CHD. Low plasma levels of HDL cholesterol were also significantly associated with CHD. Plasma triglyceride levels, age and body mass index were strong determinants of LDL cholesterol, non-HDL cholesterol, and apoB levels in men and women. In women, postmenopausal status and elevated blood pressure were also significantly associated with elevated levels of these parameters. |
| Effects of alacepril and amlodipine on the renal injury induced by a high-cholesterol diet in rats Atarashi, K., M. Takagi, et al. (1999), J Hypertens 17(12 Pt 2): 1983-6. Abstract: BACKGROUND: A high-cholesterol (HC) diet increases blood pressure and induces renal injury in rats. We compared the effects of alacepril, an ACE inhibitor, and amlodipine, a Ca antagonist, on the renal injury induced by an HC diet in rats. DESIGN AND METHODS: Male Sprague-Dawley rats were given either an HC diet only (n = 5), an HC diet and amlodipine (n = 10) or an HC diet and alacepril (n = 10). The control rats (n = 5) were given a normal diet Systolic blood pressure (SBP) was measured by a tail-cuff method. Serum lipids, malondialdehyde (MDA) as a parameter for lipid peroxidation and urinary protein excretion were determined at 0, 4 and 8 weeks. The renal injury was evaluated histologically by the glomeruli sclerosing score. RESULTS: The HC diet increased SBP. Amlodipine lowered SBP more significantly than alacepril. Serum total cholesterol was increased by the HC diet and was not affected by either anti-hypertensive agent. HDL-cholesterol was similarly decreased in the three HC diet groups. Alacepril, but not amlodipine, completely attenuated the MDA elevation induced by the HC diet. Urinary protein excretion was decreased by the two anti-hypertensive agents at a similar rate. The renal histological injury assessed by the sclerosing score was ameliorated more significantly by alacepril than by amlodipine. CONCLUSIONS: Both amlodipine and alacepril decreased blood pressure and urinary protein, and ameliorated the renal injury induced by the HC diet in rats. The renal effect of alacepril seems to be mediated by the decrease in oxidative stress as well as by reduction of blood pressure, since alacepril lowered the sclerosing score more than amlodipine and completely attenuated MDA, although the blood pressure reduction by alacepril was less than that by amlodipine. |
| Effects of alcohol and cholesterol feeding on lipoprotein metabolism and cholesterol absorption in rabbits Latour, M. A., B. W. Patterson, et al. (1999), Arterioscler Thromb Vasc Biol 19(3): 598-604. Abstract: Alcohol fed to rabbits in a liquid formula at 30% of calories increased plasma cholesterol by 36% in the absence of dietary cholesterol and by 40% in the presence of a 0.5% cholesterol diet. The increase was caused almost entirely by VLDL, IDL, and LDL. Cholesterol feeding decreased the fractional catabolic rate for VLDL and LDL apoprotein by 80% and 57%, respectively, and increased the production rate of VLDL and LDL apoprotein by 75% and 15%, respectively. Alcohol feeding had no effect on VLDL apoprotein production but increased LDL production rate by 55%. The efficiency of intestinal cholesterol absorption was increased by alcohol. In the presence of dietary cholesterol, percent cholesterol absorption rose from 34.4+/-2.6% to 44.9+/-2.5% and in the absence of dietary cholesterol, from 84.3+/-1.4% to 88.9+/-1.0%. Increased cholesterol absorption and increased LDL production rate may be important mechanisms for exacerbation by alcohol of hypercholesterolemia in the cholesterol-fed rabbit model. |
| Effects of alcohol on lipoprotein lipase, hepatic lipase, cholesteryl ester transfer protein, and lecithin:cholesterol acyltransferase in high-density lipoprotein cholesterol elevation Nishiwaki, M., T. Ishikawa, et al. (1994), Atherosclerosis 111(1): 99-109. Abstract: The mechanism whereby alcohol increases high-density lipoprotein cholesterol (HDL-C) levels is unclear. Lipoprotein lipase (LPL), hepatic lipase (HL), cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyltransferase (LCAT) act on lipoprotein metabolism. The purpose of the present study is to determine which one or what combination of these factors is responsible for the rise in HDL-C levels following alcohol ingestion. After 3 weeks of abstinence, 12 men consumed 0.5 g/kg bw of alcohol per day for 4 weeks; 13 abstaining men served as controls. Mean plasma total cholesterol (TC) levels were unchanged in either group throughout the study. Among the alcohol consumers, plasma triglycerides (TG), HDL-C, apolipoprotein (apo) A-I and A-II levels increased significantly after 3 weeks of alcohol loading but were unchanged in the control group. High-density lipoprotein3 cholesterol (HDL3-C) levels increased significantly in the alcohol consumers after 4 weeks of alcohol loading whereas high-density lipoprotein2 cholesterol (HDL2-C) levels were unaffected. In the controls, neither HDL2-C nor HDL3-C changed significantly. Post-heparin plasma (PHP) LPL activity and mass increased significantly (P < 0.01) after the alcohol ingestion (controls remained unchanged) without changing LPL specific activity. HL, CETP and LCAT activities were unaffected in both groups. We conclude that of the factors considered, LPL contributed the most to the alcohol-induced rise in HDL-C. |
| Effects of alcohol on the major steps of reverse cholesterol transport Serdyuk, A. P., V. A. Metelskaya, et al. (2000), Biochemistry (Mosc) 65(11): 1310-5. Abstract: The effects of moderate alcohol consumption on the capacity of blood sera to promote acceptance of cholesterol (C) from Fu5AH hepatoma cells, esterification of delivered free C, and transfer of produced cholesteryl esters to apolipoprotein (apo) B-containing lipoproteins have been studied. Twenty male subjects with relatively high (>50 mg/dl, n = 10) and low (<50 mg/dl, n = 10) high density lipoprotein (HDL) C levels consumed for eight weeks red grape wine (0.3 g ethanol/kg body mass per day). Alcohol consumption reduced total C and low density lipoprotein C levels in both groups of subjects. Low HDL C subjects showed an increase in HDL C, apo AI, apo AII, and lipoprotein (Lp) AI particle levels after alcohol consumption. Alcohol did not affect free C efflux from the cells. However, after the following period of substitution of alcohol with an isocaloric amount of red grape juice, cellular C efflux markedly reduced. While lecithin:cholesterol acyltransferase (LCAT) activity increased during alcohol consumption only in subjects with low HDL C, high HDL C subjects showed a significant decrease in cholesteryl ester transfer protein (CETP) activity. At the same time, alcohol consumption reduced the endogenous C esterification rate and increased the transfer of endogenous cholesteryl esters to apo B-containing lipoproteins in both groups. Thus, alcohol consumption in moderate doses enhanced the anti-atherogenicity of the serum lipoprotein spectrum, supporting more effective C efflux from peripheral cells and transport of accepted C to apo B-containing lipoproteins. The effects of alcohol on the reverse cholesterol transport depend on the initial HDL C level. |
| Effects of allyl mercaptan and various allium-derived compounds on cholesterol synthesis and secretion in Hep-G2 cells Cho, B. H. and S. Xu (2000), Comp Biochem Physiol C Toxicol Pharmacol 126(2): 195-201. Abstract: The present study was undertaken to compare the effects of allyl mercaptan (AM), a major metabolite of garlic, with several garlic constituents and extracts on cytotoxicity, cholesterol synthesis and its secretion in Hep-G2 cells. The cells were grown in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS), and treated with 5, 25, 50, 125, 250 and 500 microg/ml of AM, diallyl disulfide (DD), diallyl trisulfide (DT), steam-distilled garlic oil (SD) or vinyl-dithiin oil of garlic (VD) for 4 h. At concentrations up to 50 microg/ml, no significant cytotoxic effect was found in any group, but at concentrations above 250 microg/ml, the cell viability decreased drastically in all groups compared to the control. The treatment of cells with 25 microg/ml (non-cytotoxic concentration) of AM, DD, DT, SD for 4 h significantly inhibited 3Hacetate incorporation into cholesterol compared to that of the control (P < 0.05). The secretion of cholesterol into the medium was also significantly decreased in all groups except for VD. The treatment of cells with those allium constituents had no effect on either 3Hacetate incorporation into fatty acids or 3Hglycerol incorporation into triglyceride or phospholipid. |
| Effects of an aerobic activity program on the cholesterol levels of adolescents Rimmer, J. H. and M. A. Looney (1997), Res Q Exerc Sport 68(1): 74-9. Abstract: The purpose of this study was to determine the effects of a 15-week aerobic activity program on the total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels of 25 high school students, ages 14-17 years (experimental group = 14, control group = 11). Participants in the activity program exercised 4 days per week in a specially designed physical education class, while the control group participated in the regular physical education program. Results of the analysis of covariance found significant reductions in TC in the training group (control group Adj M = 190.2 mg/dl, experimental group Adj M = 173.1 mg/dl, p <.05), but no significant changes in HDL-C (control group Adj M = 49.8 mg/dl, experimental group Adj M = 50 mg/dl). While the exercise program appeared to have a beneficial effect on TC in 12 of 14 participants (86%), HDL-C also dropped in 12 of 14 participants (86%). |
| Effects of an American Heart Association step I diet and weight loss on lipoprotein lipid levels in obese men with silent myocardial ischemia and reduced high-density lipoprotein cholesterol Katzel, L. I., P. J. Coon, et al. (1995), Metabolism 44(3): 307-14. Abstract: Reduced plasma concentrations of high-density lipoprotein cholesterol (HDL-C) are a risk factor for coronary artery disease (CAD). In this study, we examined the sequential effects of an isocaloric American Heart Association (AHA) step I diet and a hypocaloric AHA step I diet (AHA step I diet + weight loss) on lipoprotein lipid levels in 14 middle-aged and older (60 +/- 6 years, mean +/- SD) obese (body mass index BMI > 27 kg/m2) nondiabetic men with exercise-induced silent myocardial ischemia (SI) and reduced HDL-C levels (0.85 +/- 0.14 mmol/L). Nine men of comparable age and obesity and with no evidence of exercise-induced ischemia that were evaluated longitudinally served as metabolic controls. In men with SI, after 3 months on the isocaloric AHA step I diet plasma triglyceride (TG) levels decreased by 26% (2.25 +/- 0.66 to 1.67 +/- 0.69 mmol/L, P <.005), cholesterol by 12% (5.24 +/- 0.84 to 4.62 +/- 0.78 mmol/L, P <.01), and low-density lipoprotein cholesterol (LDL-C) by 10% (3.40 +/- 0.69 to 3.05 +/- 0.70 mmol/L, P <.01). However, plasma HDL-C levels also decreased by 7% (0.85 +/- 0.14 to 0.79 +/- 0.13 mmol/L, P <.05). Subsequent weight loss (11 +/- 4 kg) in conjunction with the AHA step I diet resulted in an additional decrease of 24% in TG (P <.005), 10% in cholesterol (P <.05), and 10% in LDL-C (P <.05). Plasma HDL-C levels increased by 8% (P <.01), thereby correcting the decline seen on the AHA step I diet alone.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Effects of an antiserum to rat growth hormone and bromocriptine on cholesterol-metabolizing enzymes in the lactating rat mammary gland Shand, J. H. and D. W. West (1991), J Endocrinol 128(2): 287-95. Abstract: Rats in mid-lactation were treated, for 2 days, with anti-rat GH serum (anti-rGH) and/or bromocriptine before microsomes were prepared from the freeze-clamped mammary glands. The effects of these anti-hormone treatments on the concentrations of microsomal cholesterol and cholesterol esters and on the activities of acyl-CoA:cholesterol acyltransferase (ACAT), neutral cholesterol ester hydrolase and 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) were measured. HMG-CoA reductase was determined in microsomes prepared in both the presence and absence of phosphatase inhibitors to determine the expressed and total activities respectively. Anti-rGH reduced HMG-CoA reductase and increased microsomal cholesterol and cholesterol esters. Bromocriptine reduced HMG-CoA reductase but increased all of the other parameters. The results indicate that the initial stage in the stimulation of milk secretion involves a decrease in the activity of ACAT and that the phosphorylation level of HMG-CoA reductase is modulated by both prolactin and GH acting in opposition. |
| Effects of an educational intervention on plasma levels of LDL cholesterol in type 2 diabetics Cabrera-Pivaral, C. E., G. Gonzalez-Perez, et al. (2001), Salud Publica Mex 43(6): 556-62. Abstract: OBJECTIVE: To prove the benefit of an educational intervention for controlling LDL cholesterol levels in LDL cholesterol. MATERIAL AND METHODS: A quasi-experimental study was conducted; diabetic patients were randomly allocated to an experimental and a control group. The experimental group consisted of 25 patients and the control group of 24 patients. The educational intervention was organized through a reflection-action process. LDL cholesterol levels were measured at baseline and monthly during the nine months of the study. The groups were controlled for age and sex. Statistical analysis included Wilcoxon's test for ordinal variables. RESULTS: The intervention group had a mean value of LDL cholesterol of 148.4 +/- 21.3, compared to 185 +/- 24.1 in the control group (p < or = 0.05). CONCLUSIONS: The participative educational intervention contributed to improving the levels of LDL cholesterol, by promoting a lifestyle change in type-2 diabetic patients. |
| Effects of an ethanolic extract of Gynura procumbens on serum glucose, cholesterol and triglyceride levels in normal and streptozotocin-induced diabetic rats Zhang, X. F. and B. K. Tan (2000), Singapore Med J 41(1): 9-13. Abstract: AIM OF STUDY: The aim was to demonstrate the effects of the leaves of Gynura procumbens (Lour.) Merr. on blood sugar and lipid levels in experimental animals. METHODOLOGY: We obtained an ethanolic extract of the leaves of G. procumbens and monitored the effects of an oral administration of (i) different single doses of the extract on oral glucose tolerance in streptozotocin-induced diabetic and normal rats and (ii) fourteen doses over 7 days on serum cholesterol and triglyceride levels in streptozotocin-induced diabetic rats. Metformin and glibenclamide were used as positive control drugs. RESULTS: The extract, at single doses of 50, 150 and 300 mg/kg orally, significantly suppressed the elevated serum glucose levels in diabetic rats; 150 mg/kg was found to be the optimum hypoglycaemic dose. The extract however did not significantly suppress the elevated serum glucose levels in normal rats, unlike glibenclamide. Metformin, but not glibenclamide, improved glucose tolerance in the diabetic rats. When the optimum dose was given to diabetic rats for 7 days, the extract significantly reduced serum cholesterol and triglyceride levels in these rats. CONCLUSION: These results indicate that the leaves of G. procumbens may have biguanide-like activity. |
| Effects of an HMG-CoA reductase inhibitor on cholesterol esterification in THP-1 cells Fukuo, Y., H. Akaishi, et al. (1994), Nippon Ika Daigaku Zasshi 61(3): 251-3. |
| Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol Brousseau, M. E., E. J. Schaefer, et al. (2004), N Engl J Med 350(15): 1505-15. Abstract: BACKGROUND: Decreased high-density lipoprotein (HDL) cholesterol levels constitute a major risk factor for coronary heart disease; however, there are no therapies that substantially raise HDL cholesterol levels. Inhibition of cholesteryl ester transfer protein (CETP) has been proposed as a strategy to raise HDL cholesterol levels. METHODS: We conducted a single-blind, placebo-controlled study to examine the effects of torcetrapib, a potent inhibitor of CETP, on plasma lipoprotein levels in 19 subjects with low levels of HDL cholesterol (<40 mg per deciliter 1.0 mmol per liter), 9 of whom were also treated with 20 mg of atorvastatin daily. All the subjects received placebo for four weeks and then received 120 mg of torcetrapib daily for the following four weeks. Six of the subjects who did not receive atorvastatin also participated in a third phase, in which they received 120 mg of torcetrapib twice daily for four weeks. RESULTS: Treatment with 120 mg of torcetrapib daily increased plasma concentrations of HDL cholesterol by 61 percent (P<0.001) and 46 percent (P=0.001) in the atorvastatin and non-atorvastatin cohorts, respectively, and treatment with 120 mg twice daily increased HDL cholesterol by 106 percent (P<0.001). Torcetrapib also reduced low-density lipoprotein (LDL) cholesterol levels by 17 percent in the atorvastatin cohort (P=0.02). Finally, torcetrapib significantly altered the distribution of cholesterol among HDL and LDL subclasses, resulting in increases in the mean particle size of HDL and LDL in each cohort. CONCLUSIONS: In subjects with low HDL cholesterol levels, CETP inhibition with torcetrapib markedly increased HDL cholesterol levels and also decreased LDL cholesterol levels, both when administered as monotherapy and when administered in combination with a statin. |
| Effects of antihypertensive drugs on cholesterol metabolism of human mononuclear leukocytes and hepatoma cells Naegele, H., B. Behnke, et al. (1998), Clin Biochem 31(1): 37-45. Abstract: OBJECTIVES: Primary prevention trials of antihypertensive therapy have shown conflicting results on coronary events. Potential interference of antihypertensive agents with cellular lipid metabolism may alter the atherosclerotic risk of individuals. DESIGN AND METHODS: The effects of the calcium antagonist's verapamil, diltiazem, and nifedipine and of the beta-blockers propranolol and metoprolol on low density lipoprotein (LDL) receptor activity, cholesterol esterification rate, oleate incorporation in triglycerides and sterol synthesis were studied in freshly isolated human leukocytes and HEP G2 cells. RESULTS: Up to a concentration of 3-10 mumol/L, verapamil, propranolol, and metoprolol led to an increased cellular content of 125I-LDL by an inhibition of degradation. In mononuclear cells verapamil stimulated accumulation and degradation. No effect on binding was observed. Diltiazem was only stimulatory on 125I-LDL processing in leukocytes. Beta blockers and verapamil significantly reduced the LDL mediated 14C-oleate incorporation in cholesterol esters. In the presence of 25-hydroxycholesterol the esterification was not diminished, which suggests that cholesterolacyltransferase (ACAT) was not affected per se. Whereas all the agents induced the synthesis of lanosterol, metoprolol inhibited cholesterol synthesis. None of the agents had a significant influence on 14C-oleate incorporation in triglycerides, suggesting a specific influence on cholesterol metabolism. CONCLUSIONS: Antihypertensive drugs affect the cholesterol metabolism on a cellular level. Mechanisms are an interference with degradation of LDL and consequent alterations of cholesterol esterification. Using leukocytes as peripheral cells and HEP G2 as a model of human liver, these results may have importance when antihypertensive long-term therapy is conducted for primary or secondary prevention of atherosclerotic complications. |
| Effects of antihypertensive therapy on platelet cytosolic calcium responses to low density lipoprotein cholesterol Sowers, J. R., B. B. Raman, et al. (1996), J Hum Hypertens 10(3): 177-80. Abstract: This study examines the effects of antihypertensive therapy on platelet cytosolic calcium Ca2+i responses to low-density lipoprotein cholesterol (LDL) and vasopressin (AVP) in 15 patients (50-80 years) participating in the Hypertension Optimal Treatment International Study. All patients (diastolic blood pressure (DBP) > or = 100 mm Hg and < or = 115 mm Hg) were treated with the calcium antagonist felodipine (10 mg p.o.) with or without addition of enalapril (up to 20 mg daily as needed) to lower diastolic pressures to < 85 mm Hg. This antihypertensive therapy lowered DBP (104 +/- 0.8 to 78 +/- 1.6 mm Hg, P < 0.0001), but had no effect on basal Ca2+i or AVP-stimulated Ca2+i responses. Basal platelet Ca2+i following antihypertensive therapy (49 +/- 3.4 ng/ml) were not different from those prior to therapy (52 +/- 4.7 ng/ml). Additionally, Ca2+i responses to AVP following therapy (554 +/- 74 units) were not different from those prior to treatment (595 +/- 49 units). Following antihypertensive therapy, Ca2+i responses to 200 micrograms/ml of LDL were decreased fourfold (P < 0.05). These results suggest that antihypertensive therapy with a calcium channel blocker may potentially impact the atherogenic process by reducing the platelet Ca2+i rise, and potentially the aggregatory response, to LDL. |
| Effects of apolipoprotein A-I on ATP-binding cassette transporter A1-mediated efflux of macrophage phospholipid and cholesterol: formation of nascent high density lipoprotein particles Liu, L., A. E. Bortnick, et al. (2003), J Biol Chem 278(44): 42976-84. Abstract: The mechanism of formation of high density lipoprotein (HDL) particles by the action of ATP-binding cassette transporter A1 (ABCA1) is not defined completely. To address this issue, we monitored efflux to apoA-I of phosphatidylcholine (PC), sphingomyelin (SM), and unesterified (free) cholesterol (FC) from J774 macrophages, in which ABCA1 is up-regulated, and investigated the nature of the particles formed. The various apoA-I/lipid particles appearing in the extracellular medium were separated by gel filtration chromatography. The presence of apoA-I in the extracellular medium led to the simultaneous formation of more than one type of poorly lipidated apoA-I-containing particle: there were 9- and 12-nm diameter particles containing approximately 3:1 and 1:1 phospholipid/FC (mol/mol), respectively, which were present together with 6-nm monomeric apoA-I. Removal of the C-terminal alpha-helix (residues 223-243) of apoA-I reduced phospholipid and FC efflux and prevented formation of the 9- and 12-nm HDL particles; the apoA-I variant formed larger particles that eluted in the void volume. FC loading of the J774 cells also led to the formation of larger apoA-I-containing particles that were highly enriched in FC. Besides creating HDL particles, ABCA1 mediated release of larger (20-450-nm diameter) FC-rich particles that were not involved in HDL formation and that are probably membrane vesicles. These particles contained 1:1 PC/SM in contrast to the HDL particles, which contained 2:1 PC/SM. This is consistent with lipid raft and non-raft plasma membrane domains being involved primarily in ABCA1-mediated vesicle release and nascent HDL formation, respectively. |
| Effects of apolipoprotein E genotype on dietary-induced changes in high-density lipoprotein cholesterol in obese postmenopausal women Nicklas, B. J., R. E. Ferrell, et al. (2002), Metabolism 51(7): 853-8. Abstract: Lipid responses to a dietary intervention are highly variable between individuals. Part of this variation may be accounted for by individual differences in lipid-regulating genes that interact with diet to induce changes in lipoprotein metabolism. This study determined whether apolipoprotein E (APOE) genotype affects lipid responses to a low-fat, low-cholesterol diet in obese, postmenopausal women. Body weight and lipoprotein lipid responses to a 10-week, dietary intervention (American Heart Association AHA Step I) were compared in 61 women with the APOE 2/3 and APOE 3/3 genotype (APOE4-) and 18 women with the APOE 3/4 genotype (APOE4+) of a similar age, body composition, and maximal aerobic capacity. Body weight decreased by 2% in both groups, but changes in body weight correlated only with changes in low-density lipoprotein-cholesterol (LDL-C) (r =.27, P <.05). The dietary intervention decreased total cholesterol and LDL-C to a similar degree in both genotype groups. However, APOE4- women decreased high-density lipoprotein-cholesterol (HDL-C) by 17% +/- 11% and increased triglycerides by 20% +/- 41% in response to the diet, while APOE4+ women had a smaller decrease in HDL-C (-8% +/- 12%) and no change in plasma triglyceride. These group differences were significant for HDL-C (P <.01) and approached significance for triglycerides (P =.08). Moreover, APOE4- women decreased HDL(2)-C by 32% +/- 45%, while APOE4+ women increased HDL(2)-C by 12% +/- 62% (P <.01 between groups). It may be prudent to genotype older women before initiating low-fat diet therapy, as those with the APOE4 allele benefit the most, while the lipid profile could worsen in women without the APOE4 allele. |