To evaluate the efficacy and safety of lovastatin, new hypolipidemic agent of HMG-CoA reductase inhibitor, we administered lovastatin 40mg to 80mg once daily for 12 weeks in 20 patients(7 males, 13 females) with primary hypercholesterolemia, and observed the sequential chamges of the lipid profile every 4 weeks. The results are as follows ; 1) The seurm total cholesterol was reduced significantly by 31% from 321+/-36mg% to 210+/-26mg%(p<0.05). 2) The serum triglycerides was significantly reduced from 321+/-168mg% to 228+/-74mg% by 29%(p<0.05). 3) The low density lipoprotein cholesterol was reduced significantly from 177+/-36mg% to 120+/-22mg% by 32%(p<0.05). 4) The total lipid, high density lipoprotein cholesterol and very low density lipoprotein cholesterol were also reduced significantly. 5) The ratio between total cholesterol and high density lipoprotein cholesterol, low density lipoprotein cholesterol and high density lipoprotein cholesterol did not change after lovastatin therapy. 6) There was no adverse reaction due to lovastatin therapy during 12 weeks of therapy. These results suggested that lovastatin is a effective and safe now hypolipidemic agent and is a convenient HMG-CoA reductase inhibitor for clinical use.
Cholesterol ; Cholesterol, HDL ; Cholesterol, LDL ; Cholesterol, VLDL ; Humans ; Hypercholesterolemia* ; Lovastatin* ; Male ; Oxidoreductases ; Triglycerides

BACKGROUND: In 2001, the third report the National Cholesterol Education Program (NCEP) has concluded that LDL cholesterol levels should be a major goal for preventing coronary artery disease and atherosclerotic events. Those in the higher risk groups should then have lipoprotein analysis to determine LDL cholesterol levels. LDL cholesterol has traditionally been estimated by the Friedwald forrmula : LDL-C=total cholesterol-[high density lipoprotein cholesterol (HDL-C)+trigryceride/5]. However, when trigryceride level is >400 mg/dL, this formula is inaccurate. Therefore, We have compared the direct LDL cholesterol immunoseparation method with Friedwald formula from both normotriglyceridemic (triglyceride400 mg/dL). METHODS: The direct LDL cholesterol immunoseparation method was performed on 53 sera with triglyceride levels 61 to 1,684 mg/dL (classified as400 mg/dL : 31). Total cholesterol was measured enzymatic colorimetry. HDL cholesterol was measured in the supernatant after precipitating LDL by HDL cholesterol precipitating reagent containing dextran sulfate and magnesium chloride for serum. Direct LDL cholesterol was measured by immunoseparation method (Sigma Diagnostics, St Louis, Mo) that is based on selective absorption of HDL cholesterol and VLDL cholesterol by polystylene beads coated with goat polyclonal antibodies to human apolipoproteins. The cholesterol was measured by an enzamatic method on Hitachi 747. The linear regression and paird t-test were performed to evaluate the differences of data from Immunoseparation method and Friedwald formula. RESULTS: In triglyceridecholesterol value obtained by the direct LDL-C assay on the 22 fresh sera studied was not significantly different from that of Friedwald formula (103+/-45.1; 105+/-42.9 mg/dL). Almost identical linear regression equations for direct LDL cholesterol assay(y) and Friedwald formula(x) were obtained for samples with triglyceride400 mg/dL, the LDL cholesterol value obtained by the direct LDL-C assay on the 31 frozen sera studied was significantly different from that of Friedwald formula (103+/-38.4; 50.4+/-56.2 mg/dL). Therefore, Friedwald formula is unreliable in triglyceride>400 mg/dL. CONCLUSION: Guidelines for treatment decisions, including diet and drug initiation, and therapeutic goals for high risk groups are based entirely on the LDL cholesterol level. At triglyceride levels >400 mg/dL, Friedwald fomula is inaccurate. Immunoseparation method is more rapid, higher specific, precise and helps monitor LDL lowering drugs and diets in triglyceride level>400 mg/dL.
Absorption ; Antibodies ; Apolipoproteins ; Cholesterol* ; Cholesterol, HDL ; Cholesterol, LDL ; Cholesterol, VLDL ; Colorimetry ; Coronary Artery Disease ; Dextran Sulfate ; Diet ; Education ; Goats ; Humans ; Linear Models ; Lipoproteins* ; Magnesium Chloride ; Triglycerides

A myriad of the retrospective studies have shown the benefit of hormone replacement therapy (HRT) on cardiovascular disease. It has been consistently shown that estrogen decreases total and LDL cholesterol, but increases the HDL cholesterol, resulting in a favorable cardiovascular outcome. In addition, it has been reported that estrogen has a beneficial role toward vascular function. The benefit of HRT on cardiovascular disease did not become a matter for suspicion or skepticism until the arrival of primary and secondary prevention clinical trial data. A large body of evidence from secondary prevention trials, such as HERS, EVA and WAVE, revealed that HRT has no beneficial effect at all toward cardiovascular disease protection; conversely, it was revealed to even be harmful. HRT increased the risk of CHD, DVT and strokes, as well as of cancers in postmenopausal women with CHD, with the worst evidence coming from a primary prevention trial. The Women's Health Initiative (WHI) study, the largest of the HRT trials, revealed the same findings as those of secondary prevention trials. In this trial, HRT significantly increased the risks of CHD, DVT, strokes and cancers, further confirming the previous findings. The lack of benefit of HRT in those trials can not be explained by the beneficial influence of HRT on the lipid profile and vascular function. Many researchers that still regard HRT as cardioprotective argue that the route, combination of drugs or even the dose of the drug administered would make differences. However, it is the increased VLDL synthesis and risk of thrombosis that make HRT harmful. HRT increase, VLDL synthesis that results in the generation of atherogenic small dense LDL and thrombus formation. In addition, HRT increases the risk of thrombosis by activating the coagulation pathway independently of VLDL synthesis. It has been reported that transdermal estrogen therapy does not increase VLDL synthesis or thrombus formation, being allegedly beneficial. However, it should not be forgotten that even the present data is not decisive and not confirmative for performing another new clinical trial of HRT being potentially harmful
Cardiovascular Diseases* ; Cholesterol, HDL ; Cholesterol, LDL ; Cholesterol, VLDL ; Estrogens ; Extravehicular Activity ; Female ; Hormone Replacement Therapy* ; Humans ; Primary Prevention ; Retrospective Studies ; Secondary Prevention ; Stroke ; Thrombosis ; Women's Health

OBJECTIVETo evaluate the association between very low density lipoprotein cholesterol (VLDL-C) and cholesterol absorption and synthesis markers in patients with moderate and high risk of coronary heart disease.

METHODSA total 363 statin-naïve patients with moderate and high risk of coronary heart disease were consecutively recruited from two hospitals in Shanxi and Henan provinces between October 2008 and June 2009. A standard questionnaire and physical examination were performed at baseline. Atorvastatin (20 mg/day) was administered to patients for 4 weeks. Venous blood samples after an overnight fast were collected before and after treatment for measuring VLDL-C and cholesterol absorption and synthesis markers. In qualitative analyses, the baseline level of cholesterol absorption and synthesis markers and their reduction after atorvastatin treatment were categorized into 3 tertile groups.

RESULTS(1) Of 363 patients, 283 patients with mean age of (55.43±9.01)years old with complete data were finally analyzed. The median level of baseline VLDL-C was 1.06 (0.65, 1.86) mmol/L. The median level of baseline cholesterol absorption marker (Campesterol) and cholesterol synthesis marker (Lathosterol) was 6.01 (3.78, 9.45) mg/L and 13.46 (8.30, 21.07) mg/L, respectively. (2) Partial correlation analysis and multiple regression showed the baseline level of VLDL-C was positively correlated with Campesterol (r=0.153, P<0.05) but not with Lathosterol(r=0.182, P=0.173). Furthermore, baseline VLDL-C level significantly increased with tertile of the baseline level of Campesterol in the qualitative analyses(P for trend=0.035). (3) Mean reduction in VLDL-C levels was 38.0% after 4 weeks atorvastatin treatment. VLDL-C reduction was positively correlated with Campesterol reduction (r=0.331, P<0.001). VLDL-C reduction significantly increased with the tertile of Campesterol reduction (P for trend=0.032). But this trend was not observed between VLDL-C level and Lathosterol (P for trend=0.798).

CONCLUSIONThe level of VLDL-C was closely related to cholesterol absorption marker, and further studies are needed to validate if inhibitor of cholesterol absorption (for example by Ezetimibe) could bring about more effective VLDL-C lowering effect in this patient cohort.

Atorvastatin Calcium ; Biomarkers ; Cholesterol ; analogs & derivatives ; Cholesterol, LDL ; Cholesterol, VLDL ; Coronary Artery Disease ; Ezetimibe ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Phytosterols ; Risk Factors

We report a case of type III hyperlipoproteinemia associated with xanthoma eruptivum. Xanthoma tuberosum, and xanthoma striatum palmare whose clinical symptoms have been improved by the treatment of gemfibrozil. A 31-year-old male patient visited our clinic for evaluation of multiple yellowish nodules on the elbows, multiple yellowish plaques on the buttocks and linear yellowish plaques along with the palmar creases on both palms. The blood chemistry showed an elevation of cholesterol and triglyceride. Lipoprotein electrophoresis showed broad betazone and plasma standing test showed turbid plasma. Lipoprotein ultracentrifugation showed that the ratio of VLDL cholesterol and plasma triglyceride was 0.38. According to the above findings, we diagnosed this patient as type III hyperlipoproteinemia. After 4 months of treatment with diet and gemfibrozil, the serum level of cholesterol and triglyceride were reduced to normal range. The skin lesions of both palms showed marked improvement but the skin lesions on elbows and buttocks were not much improved.
Adult ; Buttocks ; Chemistry ; Cholesterol ; Cholesterol, VLDL ; Diet ; Elbow ; Electrophoresis ; Gemfibrozil ; Humans ; Hyperlipoproteinemia Type III* ; Lipoproteins ; Male ; Plasma ; Reference Values ; Skin ; Triglycerides ; Ultracentrifugation ; Xanthomatosis*

Lipoprotein lipase (LPL) is known to be attached to the luminal surface of vascular endothelial cells in a complex with membrane-bound heparan sulfate, and released into blood stream by heparin. LPL that catalyzes hydrolysis of triglyceride (TGL) on chylomicron and VLDL into two fatty acids and monoacylglycerol, is also implicated to participate in an enhancement of cholesterol uptake by arterial endothelial cells in vitro. But little is known about the LPL-mediated cholesterol uptake in physiological state. In this study, changes in blood lipid composition and levels of lipoproteins were determined after the injection of heparin in human. The level of LPL in plasma was increased from 0 to 11 mU/ml within 30-40 min post-heparin administration and decreased to the basal level within 2 h. The level of TGL in plasma decreased from 70 mg/dl to 20 mg/dl within 1 h and gradually increased to 80 mg/dl within 4 h. However the level of total cholesterol in plasma remained at 140 mg/dl during an experimental period of 4 h. Analysis of Lipoproteins in plasma by NaBr density gradient ultracentrifugation showed that the level of VLDL decreased from 50 mg/dl to 10 mg/dl within 1-2 h and returned to normal plasm level at 4 h. However there were no significant changes in the level of LDL and HDL. These results suggest that, at least, in normo-lipidemic subjects, increased free plasm LPL acts primarily on VLDL and failed to show any significant uptake of cholesterol-rich lipoproteins in human.
Adult ; Cholesterol/blood ; Heparin/pharmacology* ; Heparin/administration & dosage ; Human ; Immunoblotting ; Lipoprotein Lipase/blood* ; Lipoproteins/blood* ; Lipoproteins, HDL/blood ; Lipoproteins, LDL/blood ; Lipoproteins, VLDL/blood ; Triglycerides/blood

The role of very low density lipoprotein receptor (LVLDR) in the process of foam cell formation was investigated. After the primary cultured mouse peritoneal macrophages were incubated with VLDL, beta-VLDL or low density lipoprotein (LDL), respectively for 24 h and 48 h, foam cells formation was identified by oil red O staining and cellular contents of triglyceride (TG) and total cholesterol (TC) were determined. The mRNA levels of LDLR, LDLR related protein (ILRP) and VLDLR were detected by semi-quantitative RT-PCR. The results demonstrated that VLDL, beta-VLDL and LDL could increase the contents of TG and TC in macrophages. Cells treated with VLDL or beta-VLDL showed markedly increased expression of VLDLR and decreased expression of LDLR, whereas LRP was up-regulated slightly. For identifying the effect of VLDL receptor on cellular lipid accumulation, ldl-A7-VR cells, which expresses VLDLR and trace amount of LRP without functional LDLR, was used to incubate with lipoproteins for further examination. The results elucidated that the uptake of triglyceride-rich lipoprotein mediated by VLDLR plays an important role in accumulation of lipid and the formation of foam cells.
Animals ; Arteriosclerosis ; metabolism ; pathology ; Cells, Cultured ; Cholesterol, LDL ; metabolism ; pharmacology ; Female ; Foam Cells ; cytology ; metabolism ; Lipoproteins, VLDL ; pharmacology ; Macrophages, Peritoneal ; cytology ; metabolism ; Mice ; Receptors, LDL ; metabolism ; Triglycerides ; metabolism

MED1 is a key transcription co-activator subunit of the Mediator complex that is essential for RNA polymerase II-dependent transcription. MED1 functions as a co-activator for PPARs and other nuclear receptors and transcription factors, and plays an important role in lipid metabolism. To examine how MED1 might affect plasma lipids, plasma triglyceride, cholesterol levels, and lipoprotein profiles, were measured in MED1(deltaLiv) mice fasted for 24, 48 and 72 hours. Histological changes in liver sections from MED1(deltaLiv) mice after 72 hours of fasting were also examined using H&E staining. There was no fat accumulation in livers of MED1(deltaLiv) mice compared to MED1(fl/fl) and PPARalpha -/- control mice after 72 hours of fasting. Compared with MEDl(fl/fl) mice, plasma triglycerides in MED1(deltaLiv) mice were significantly increased after 24, 48 and 72 hours of fasting, and plasma cholesterol was significantly increased after 48 and 72 hours of fasting. Lipoprotein profiles were similar in fed MED1(fl/fl) and MED1(deltaLiv) mice. However, very low density lipoprotein (VLDL) was significantly increased in MED1(deltaLiv) mice after 24 hours of fasting. We conclude that, hyperlipidemia in MED1(deltaLiv) mice in response to fasting is due to the accumulation of VLDL, which suggests that MED1 plays a pivotal role in the regulation of plasma triglyceride and cholesterol levels.
Animals ; Cholesterol ; blood ; Fasting ; Hyperlipidemias ; blood ; Lipoproteins, VLDL ; blood ; Liver ; chemistry ; Mediator Complex Subunit 1 ; genetics ; physiology ; Mice ; Mice, Knockout ; Triglycerides ; blood

OBJECTIVETo study the influence of soybean phytochemical extract containing isoflavones and soyasaponins (SPE) on blood glucose, blood lipids, plasma lipid peroxide and platelet aggregation activity in diabetic rats.

METHODSDiabetic rats were fed with fodder containing 20 g/kg of SPE for 20 weeks. Their plasma very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) were separated by sequential ultracentrifugation.

RESULTSTwenty weeks after experiment, level of blood glucose, atherosclerotic index and plasma level of lipid peroxide were (11.9 +/- 0.9) mmol/L, 0.40 +/- 0.14 and (15.7 +/- 0.5) mmol/L, respectively in diabetic rats fed with SPE, significantly lower than those in control rats not fed with it, (14.2 +/- 2.0) mmol/L, 0.58 +/- 0.22 and (20.7 +/- 3.0) mmol/L, respectively. Accordingly, platelet aggregation rates induced by ADP and collagen in the two groups were (54.1 +/- 8.8)% vs (66.6 +/- 12.4)% and (58.0 +/- 7.9)% vs (69.6 +/- 9.4)%, respectively. Changes in all these indices were significantly different between the two groups.

CONCLUSIONSPE could significantly decrease blood glucose, improve atherosclerotic index, and inhibit lipid peroxidation and platelet aggregation in diabetic rats, which might be useful in prevention and control of diabetes mellitus and diabetes-associated atherosclerosis.

Animals ; Arteriosclerosis ; blood ; prevention & control ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Cholesterol, VLDL ; blood ; Diabetes Mellitus, Type 2 ; blood ; prevention & control ; Flavonoids ; pharmacology ; Male ; Phytotherapy ; Random Allocation ; Rats ; Saponins ; pharmacology ; Soybeans ; Triglycerides ; blood

This study was undertaken to examine effects of dietary intake of garcinia cambogia extract, soy peptide and L-carnitine mixture on body weight gain and obesity-related bio-markers in rats fed high-fat diet for 9 weeks with or without regular treadmill exercise. Forty 5-week-old male Sprague-Dawley rats were randomly divided into four groups; sedentary control group (SC), exercised control group (EC), sedentary formula-fed group (SF), and exercised formula-fed group (EF). The SC and EC rats were fed high-fat control diet (fat comprises 40% of total caloris), and SF and EF rats were fed high-fat formula (composed of garcinia cambogia, soy peptide and L-carnitine) supplemented diet. Statistical analyses by two-way ANOVA indicated that the regular treadmill exercise significantly lowered cumulative body weight gain, total visceral fat mass, and epididymal, perirenal and retroperitoneal fat pad weights, and serum concentrations of total cholesterol and LDL + VLDL cholesterol, insulin, c-peptide and leptin. Feeding the formula also resulted in significant reductions in cumulative body weight gain and visceral fat pad weights, along with other related parameters including serum total and LDL + VLDL cholesterol levels, and hepatic enzyme activities involved in fatty acid synthesis. Statistical analyses by one-way ANOVA revealed that the formula consumption significantly improved body weight gain (18% reduction), total visceral fat weight (20% reductions), and serum total (43% reduction) and LDL + VLDL cholesterol (54% reduction) levels, as well as serum levels of insulin (49% reduction), and c-peptide (41% reduction) in sedentary rats, but failed to exhibit significant reductions in these indices in animals under treadmill exercise program. Taken together, these results suggest that the treadmill exercise per se exhibited significant improvements in body fat reduction and other related bio-markers, and so the formula consumption did not achieve a further significant reductions in these bio-markers in exercised rats. Nevertheless, animals fed the formula with regular exercise showed the most efficient weight reduction compared to other groups either fed formula without exercise or received regular exercise without dietary supplementation.
Adipose Tissue ; Animals ; Body Weight* ; C-Peptide ; Carnitine* ; Cholesterol ; Cholesterol, VLDL ; Diet ; Diet, High-Fat* ; Dietary Supplements ; Garcinia cambogia* ; Garcinia* ; Humans ; Insulin ; Intra-Abdominal Fat ; Leptin ; Male ; Rats* ; Rats, Sprague-Dawley ; Weight Loss ; Weights and Measures