The cholesterol lowering effect of antimalarial drugs is enhanced in patients with lupus taking corticosteroid drugs.

Rahman P, Gladman DD, Urowitz MB, Yuen K, Hallett D, Bruce IN.

University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, The Toronto Hospital, Ontario, Canada.

OBJECTIVE: To examine the relationship between antimalarial therapy and total cholesterol in patients with systemic lupus erythematosus (SLE) with or without steroid therapy. METHODS: Retrospective study for the University of Toronto Lupus Clinic database between 1976 and 1997. The effects of antimalarials on random total cholesterol levels were assessed in the following situations: patients not receiving steroids (part I) that either initiated or discontinued antimalarials; patients receiving steroids (part II) that were either on a stable dose or initiating antimalarials; and patients initiating steroids with or without antimalarials (part III). Paired t test, Fisher's exact test, and 2 way analysis of variance were used when appropriate. RESULTS: Initiation of antimalarials reduced the baseline total cholesterol by 4.1 % at 3 months in 53 patients (p = 0.020) and by 0.6% at 6 months in 30 patients (p = NS), while the cessation of antimalarials increased the total cholesterol by 3.6% at 3 months in 38 patients (p = NS) and 5.4% at 6 months in 22 patients (p = NS). In 181 patients taking steroids and antimalarials, the mean total cholesterol was 11% less than for 201 patients receiving a comparable dose of steroids alone (p = 0.0023). Initiation of antimalarials on a stable dose of steroids reduced the total cholesterol by 11.3% at 3 months in 29 patients (p = 0.0002) and 9.4% at 6 months in 20 patients (p = 0.004). For patients initiating steroids, the percentage increase in cholesterol was lower in those taking antimalarials compared to patients without antimalarial therapy (p = 0.0149). CONCLUSION: Antimalarials lower total cholesterol in patients receiving steroids and may minimize steroid induced hypercholesterolemia.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9972966&dopt=Abstract cholesterol




Lipid profile of rats fed blends of rice bran oil in combination with sunflower and safflower oil.

Sunitha T, Manorama R, Rukmini C.

Department of Foods and Nutrition, Post Graduate and Research Centre, Acharya N.G. Ranga, Agriculture University, Rajendranagar, Hyderabad, India.

This study was undertaken to assess the effect of blended oils, i.e., polyunsaturated fatty acid (PUFA) rich vegetable oils like safflower oil (SFO) and sunflower oil (SNO) with the unconventional and hypocholesterolemic rice bran oil (RBO) on the serum lipid profile of rats. Rats fed RBO+SNO/SFO at 70:30 ratio for a period of 28 days showed significantly (p < 0.05) lower levels of total cholesterol (TC), triglycerides (TG) and low density lipoprotein (LDL) cholesterol and increased high density lipoprotein (HDL) cholesterol in animals fed a high cholesterol diet (HCD) and cholesterol free diet (CFD). Liver total cholesterol (TC) and triglycerides (TG) were also reduced. Fecal excretion of neutral sterols and bile acids was increased with use of RBO blends. RBO, which is rich in tocopherols and tocotrienols, may improve the oxidative stability of the blends. Tocotrienols are known to inhibit 3-hydroxy, 3-methyl, glutaryl CoA (HMG-COA) reductase (rate limiting enzyme in cholesterol biosynthesis), resulting in hypocholesterolemia. In addition to improving the lipid profile by lowering TC, TG and LDL-C and increasing HDL-C, blending of RBO with other oils can result in an economic advantage of lower prices.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9629862&dopt=Abstract cholesterol




Serum lipid concentrations change with serum alkaline phosphatase activity during pregnancy.

Choi JW, Pai SH.

Department of Clinical Pathology, College of Medicine, Inha University Hospital, Inchon, Korea. jwchoi inha.ac.kr

To investigate the relationship between serum lipids and alkaline phosphatase during normal pregnancy, we measured triglyceride, total cholesterol, HDL-cholesterol, and LDL-cholesterol concentrations and alkaline phosphatase activity in serum samples from 546 apparently healthy pregnant, postpartum, and nonpregnant women. Serum HDL-cholesterol levels did not change significantly during pregnancy, but serum triglyceride, total cholesterol, LDL-cholesterol, and alkaline phosphatase levels increased gradually as pregnancy proceeded, reached maximum values in the third trimester, and returned to nonpregnant levels by 20-24 wk postpartum. The serum alkaline phosphatase activity averaged 2.1-fold higher in the late third trimester than in the first trimester; the serum triglyceride concentration averaged 2.3-fold higher in the late third trimester than in the first trimester. Compared to the peak values during pregnancy, serum alkaline phosphatase activity averaged 45% lower and serum triglyceride level averaged 47% lower at 12-16 wk postpartum. The serum alkaline phosphatase activity was correlated with the serum concentrations of total cholesterol (r = 0.68, p < 0.01) and triglyceride (r = 0.71, p < 0.01). In short, this study shows that serum triglyceride and total cholesterol levels change in parallel with serum alkaline phosphatase activity during and after normal pregnancy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11045767&dopt=Abstract cholesterol




alpha-Tocopherol concentrations in plasma but not in lipoproteins fluctuate during the menstrual cycle in healthy premenopausal women.

Lanza E, Forman MR, Johnson EJ, Muesing RA, Graubard BI, Beecher GR.

Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Because premenopausal women experience cyclic fluctuations of plasma carotenoids and their lipoprotein carriers, it was hypothesized that plasma alpha-tocopherol (A-T) fluctuates by phase of the menstrual cycle. Twelve free-living women, with a confirmed ovulatory cycle, were given a controlled diet for two consecutive menstrual cycles. Blood was drawn during the menses, early follicular, late follicular and luteal phases to simultaneously measure serum hormones, plasma lipoproteins and A-T concentrations, and A-T distribution in the lipoprotein fractions. Plasma A-T concentrations were significantly lower during menses than during the luteal phase by approximately 12% in each controlled diet cycle (P < 0.001). Adjustment for serum cholesterol and triglyceride concentrations did not alter these findings. The distributions of A-T in lipoprotein cholesterol fractions were not significantly different by menstrual phase. From 61 to 62% of A-T was concentrated in the LDL fraction, with another 9-14% in HDL2, 17-22% in HDL3 and the remaining 6-8% in VLDL+ IDL. There were no significant differences in lipoprotein cholesterol fractions by menstrual phase, except for a significant increase (P = 0.03) in HDL2 cholesterol from the early follicular to the late follicular phase. Spearman rank correlations from data during the second controlled diet month showed A-T in HDL2 in the late follicular phase was positively correlated with HDL cholesterol in the early follicular (r = 0.88), late follicular (r = 0.86) and luteal phases (r = 0.86) and with luteal apolipoprotein (ApoA-1) level (r = 0.90), and luteal HDL2 cholesterol (r = 0.83). A-T in HDL3 in the early follicular phase was negatively correlated with HDL2 cholesterol (r = -0.96) and ApoA-1 (r = -0.85), whereas luteal A-T in HDL3 was correlated with luteal HDL3 cholesterol (r = -0.79). Late follicular A-T in VLDL was positively correlated with early follicular HDL3 cholesterol and late follicular HDL3 cholesterol (r = 0.83). Fluctuations of A-T concentrations by phase of the menstrual cycle should be taken into consideration in future research concerning premenopausal women and the risk of chronic disease.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9649599&dopt=Abstract cholesterol




Apolipoprotein E2 reduces the low density lipoprotein level in transgenic mice by impairing lipoprotein lipase-mediated lipolysis of triglyceride-rich lipoproteins.

Huang Y, Liu XQ, Rall SC Jr, Mahley RW.

Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California 94141-9100, USA.

Apolipoprotein (apo) E2 is often associated with low levels of low density lipoprotein (LDL) cholesterol and high levels of plasma triglycerides in humans. Mice expressing apoE2 also have low LDL levels. To evaluate the possible role of the LDL receptor in the cholesterol-lowering effect of apoE2, we bred transgenic mice expressing low levels of apoE2 with LDL receptor-null mice (hE2(+/0), LDLR-/-). Even in the absence of the LDL receptor, plasma total and LDL cholesterol levels decreased progressively with increasing levels of plasma apoE2. At plasma apoE2 levels >20 mg/dl, LDL cholesterol was approximately 45% lower than in LDLR-/- mice. Thus, the LDL cholesterol-lowering effect of apoE2 is independent of the LDL receptor. In contrast, plasma triglyceride levels increased (mostly in very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL)) progressively as apoE2 levels increased. At plasma apoE2 levels >20 mg/dl, triglycerides were approximately 150% higher than in LDLR-/- mice. Furthermore, in apoE-null mice (hE2(+/0), mE-/-), apoE2 levels also correlated positively with plasma triglyceride levels, suggesting impaired lipolysis in both hE2(+/0),LDLR-/- and hE2(+/0),mE-/- mice. Incubating VLDL or IDL from the hE2(+/0),LDLR-/- or the hE2(+/0),mE-/- mice with mouse postheparin plasma inhibited lipoprotein lipase-mediated lipolysis of apoE2-containing VLDL and IDL by approximately 80 and approximately 70%, respectively, versus normal VLDL and IDL. This observation was confirmed by studies with triglyceride-rich emulsion particles, apoE2, and purified lipoprotein lipase. Furthermore, apoE2-containing VLDL had much less apoC-II than normal VLDL. Adding apoC-II to the incubation partially corrected the apoE2-impaired lipolysis in apoE2-containing VLDL or IDL and corrected it completely in apoE2-containing emulsion particles. Thus, apoE2 lowers LDL cholesterol by impairing lipoprotein lipase-mediated lipolysis of triglyceride-rich lipoproteins (mostly by displacing or masking apoC-II). Furthermore, the effects of apoE2 on both plasma cholesterol and triglyceride levels are dose dependent and act via different mechanisms. The increase in plasma cholesterol caused by apoE2 is due mostly to impaired clearance, whereas the increase in plasma triglycerides is caused mainly by apoE2-impaired lipolysis of triglyceride-rich lipoproteins.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9651338&dopt=Abstract cholesterol




An investigation of the relationship between estrogen, estrogen metabolites and blood cholesterol levels in ovariectomized rats.

Liu D, Bachmann KA.

Department of Pharmacology, College of Pharmacy, University of Toledo, Ohio, USA.

17 beta-Estradiol (E2) has long been known for protecting against coronary heart disease by lowering cholesterol levels in premenopausal women. A recent study in our laboratory suggested that two hydroxylated metabolites of E2 possess similar hypocholesterolemic effects in male rats. This effect has been further investigated with additional estrogen metabolites in ovariectomized rats with a view toward mimicking the true postmenopausal situation in humans. Their effects in reproductive tissues were also evaluated histologically. Fundamentally, the following issues were addressed: (1) Do oxidized metabolites of estradiol lower total cholesterol levels? (2) Can a hypocholesterolemic effect be achieved without eliciting estrogenic activities on reproductive tissues? The results of this investigation showed that a number of oxygenated metabolites of estradiol can lower cholesterol levels. Among them, 4-hydroxyestradiol (4-OHE2) produced a striking hypocholesterolemic effect and a substantial uterotropic effect. 2-Hydroxyestradiol (2-OHE2), 2-methoxyestradiol (2-meoE2) and 2-methoxyestrone (2-meoE1) produced a significant decrease in cholesterol levels at doses that did not produce significant uterotropic effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9655903&dopt=Abstract cholesterol




High-density lipoprotein particles are large in patients with variant angina.

Miwa K, Yoshida N, Nakagawa K, Inoue H.

Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.

OBJECTIVE: Dyslipidemia in patients with coronary vasospasm may be characterized by low level of high-density lipoprotein (HDL)-cholesterol as well as apolipoprotein (apo) A-I but not high level of low-density lipoprotein-cholesterol. This study sought to examine the HDL particle size in patients with variant angina. METHODS: The HDL particle size was examined by analyzing serum lipid levels in 38 patients with variant angina to compare with those of 40 control subjects and 30 normocholesterolemic patients with stable effort angina. Also, actual HDL size distribution was assessed by electrophoresis. RESULTS: The HDL-cholesterol, apoA-I and apoA-II levels were all lower (P < 0.01 for each) in patients with variant angina and patients with stable effort angina as compared with control subjects. The apoA-II level was lower (P < 0.01) in patients with variant angina than in patients with stable effort angina. The apoA-I/apoA-II ratio was lower (P < 0.01) in patients with stable effort angina, but not in patients with variant angina as compared with control subjects. In contrast, the HDL-cholesterol/apoA-I ratio was higher in patients with variant angina than in control subjects (P < 0.01) and also patients with stable effort angina (P < 0.01). The slope of the regression line, comparing HDL-cholesterol and apoA-I levels, was greater in patients with variant angina than in control subjects (P < 0.05) and patients with stable effort angina (P < 0.05), suggesting an increase in larger HDL particles. Native polyacrylamide gel electrophoresis revealed that HDL particles in patients with variant angina were skewed towards larger sizes compared with control subjects (P < 0.01) and patients with stable effort angina (P < 0.01). The abnormal serum lipid values were normalized in the patients with variant angina after the medical treatment and inactivation of the coronary spasm. CONCLUSION: High HDL-cholesterol/apoA-I levels associated with low serum HDL-cholesterol and apoA-I levels were characteristic in patients with variant angina, in whom HDL particles were large, cholesterol-rich and possibly malfunctioning.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9659457&dopt=Abstract cholesterol




[Effect of eggplant on plasma lipid levels, lipidic peroxidation and reversion of endothelial dysfunction in experimental hypercholesterolemia]

[Article in Portuguese]

Jorge PA, Neyra LC, Osaki RM, de Almeida E, Bragagnolo N.

Faculdades de Ciencias Medicas, UNICAMP, Campinas, SP.

PURPOSE: To study the effect of egg plant on endothelium-dependent relaxation, and plasma lipids in hypercholesterolemic rabbits, and to assess influence of this plant on the malondialdehyde (MDA) content of LDL particles and the arterial wall. METHODS: Thirteen male rabbits were randomly assigned to control (C), hypercholesterolemic (H) and egg plant (E) treated groups (n = 10 each). The H and E rabbits were fed a diet supplemented with cholesterol (0.5%) and coconut oil (10%) for 4 weeks. In addition, group E received 10 mL of the fruit juice/day during the last 2 weeks. The animals were killed and the aorta removed to measure MDA content and the endothelium dependent relaxation responses. Total plasma cholesterol, VLDL, LDL, HDL and triglyceride levels were determined using commercial kits. MDA was quantified in native and oxidized LDL and in the arterial wall. RESULTS: After 4 weeks, the E group rabbits had a significantly lower weight, plasma cholesterol, LDL, triglyceride and aortic cholesterol content than group H(p < 0.05). The MDA content that was significantly increased in the LDL particles and in the arterial wall of H rabbits was reduced in the E group (p < 0.05). Endothelium-dependent relaxation were significantly higher in the E group compared H group rabbits (p < 0.05). CONCLUSION: In hypercholesterolemic rabbits egg plant juice significantly reduced weight, plasma cholesterol levels, aortic cholesterol content and the MDA concentrations in native-oxidized LDL and in the arterial wall and increased the endothelium-dependent relaxations.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9659714&dopt=Abstract cholesterol




Dietary sitostanol reduces plaque formation but not lecithin cholesterol acyl transferase activity in rabbits.

Ntanios FY, Jones PJ, Frohlich JJ.

School of Dietetics and Human Nutrition, McGill University, Macdonald Campus, Ste-Anne-de-Bellevue, Quebec, Canada.

The effects of graded amounts of dietary sitostanol (0.01, 0.2 and 0.8% (w/w)) were examined on plasma lipid-profile, coronary artery plaque development and lecithin:cholesterol acyl transferase activity in male New Zealand White rabbits given semi-purified diets for 10 weeks. All diets provided < 10% energy in the form of fat and contained 0.5% (w/w) cholesterol (C). Rabbits fed the semi-purified diet with 0.8% (w/w) (0.64 g/day) sitostanol had lower plasma total cholesterol (TC) (p = 0.006) (15.2 +/- 4.80 mmol/l) and very low-density lipoprotein-cholesterol (VLDL-C) (p = 0.007) (6.31 +/- 3.11 mmol/l) levels compared to the atherogenic control group (n = 6) (29.6 +/- 5.52 and 17.16 +/- 7.43 mmol/l, respectively). Dietary sitostanol at 0.8% (w/w) depressed plaque accretion in coronary arteries (p = 0.0014) and ascending aorta (p = 0.0004) compared with the atherogenic control, 0.01 and 0.2% (w/w) sitostanol-fed groups. No differences (p = 0.24) in the activity of lecithin:cholesterol acyl transferase (LCAT) were observed across groups, although plasma cholesterol fractional esterification rate was higher (p = 0.004) in the 0.8% (w/w) sitostanol fed animals compared with the atherogenic control. Significant negative correlations were demonstrated between sitostanol intake and plasma TC, LDL-C and VLDL-C levels. Hepatic campesterol levels were correlated (r = 0.3, p = 0.03) with plasma but not hepatic TC concentrations. These results demonstrate that dietary sitostanol at a concentration of 0.8% (w/w) or 0.64 g/day lowered plasma cholesterol levels and depressed atherosclerosis development in rabbits, but did not alter LCAT activity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9678775&dopt=Abstract cholesterol