Objective: We evaluated the safety and efficacy of lipoprotein apheresis (LA) in patients with familial hypercholesterolemia (FH) who can't reach low-density lipoprotein cholesterol(LDL-C) target goals with the maximal tolerated dose of lipid-lowering agents. Methods: This was a retrospective cross-sectional study. Between February 2015 and November 2019, patients with FH who were admitted in Fuwai hospital and treated with LA were consecutively enrolled. Based on intensive lipid-lowering agents, these patients received LA by double filtration plasma pheresis (DFPP) method. The changes of lipid levels such as LDL-C and lipoprotein(a)[Lp(a)] were compared before and after LA treatment, and the changes of immunoglobulin (Ig) concentration and LA-related adverse effects were also discussed. Results: A total of 115 patients with FH were enrolled in this study, of which 8 cases were homozygous FH and 107 cases were heterozygous FH. The age was (43.9±12.2) years and there were 75 (65.2%) males, and 108 (93.8%) with coronary artery disease. For pre-and immediately after LA treatment, the LDL-C was (5.20±2.94) mmol/L vs. (1.83±1.08) mmol/L, Lp(a) concentration was 428.70(177.00, 829.50)mg/L vs. 148.90(75.90, 317.00) mg/L (P<0.001), with a decrease of 64.2% and 59.8% respectively. The levels of IgG and IgA measured 1 day after LA treatment were both in the normal range and IgM concentration was below the reference value, the reductions of which were 15.1%, 25.0% and 58.7% respectively (P<0.001). Six patients had mild symptoms of nausea, hypotension dyspnea and palpitation, the symptoms were relieved by symptomatic treatment. Conclusion: For patients with FH who do not achieve LDL-C target goal with the maximal tolerated lipid-lowering agents, especially those with elevated Lp(a) levels, LA, which can significantly further reduce LDL-C and Lp(a) levels, is an effective and safe option.
Adult ; Blood Component Removal/methods* ; Cholesterol, LDL ; Cross-Sectional Studies ; Female ; Humans ; Hyperlipoproteinemia Type II/therapy* ; Lipoprotein(a)/chemistry* ; Lipoproteins/chemistry* ; Male ; Middle Aged ; Retrospective Studies

The saponins in different parts of Gynostemma pentaphyllum were analyzed via UPLC-Q-TOF-MS~E. A total of 46 saponins were identified, and the underground part had 26 saponins more than the aboveground part, most of which were trisaccharide saponins. The rat model of hyperlipidemia was established with high-fat diet. This study explored the lipid-lowering activity of total saponins in the underground part of G. pentaphyllum, so as to provide a theoretical basis for the comprehensive utilization of the underground part of G. pentaphyllum. A total of 99 healthy SD rats were randomly assigned into a blank group, a model group, a positive drug group, an aboveground total saponins group, and low-, medium-, and high-dose underground total saponins groups. Except the blank group, the other groups were fed with high-fat diet for 6 weeks. Then, the blood was collected from the orbital cavity to determine whether the modeling was successful according to the serum levels of total cholesterol(TC) and triglyceride(TG). After intragastric administration of the corresponding agents for 30 continuous days, the physical state of the rats were observed, and the body weight and liver specific gravity were measured. Furthermore, the levels of TC, TG, low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), alanine transaminase(ALT), aspartate transaminase(AST), bilirubin, and total bile acids in serum, as well as the levels of superoxide dismutase(SOD), malondialdehyde(MDA), peroxidase proliferator-activated receptor(PPAR-γ) in the liver tissue, were determined. The pathological changes of liver was observed via HE staining. The results showed that the aboveground total saponins and medium-and high-dose underground total saponins can treat hepatocyte steatosis, lower TC, TG, LDL-C, ALT, AST, total bilirubin, MDA, and PPAR-γ levels, and increase HDL-C and SOD levels in the model rats. The effect tended to be more obvious with the increase in dosage. Therefore, the total saponins in the underground part of G. pentaphyllum have good pharmacological effect of reducing blood lipid, which provides a theoretical basis for the comprehensive utilization of the underground part of G. pentaphyllum.
Alanine Transaminase/analysis* ; Animals ; Aspartate Aminotransferases/analysis* ; Bile Acids and Salts/blood* ; Bilirubin/blood* ; Cholesterol, LDL/blood* ; Diet, High-Fat/adverse effects* ; Gynostemma/chemistry* ; Hypolipidemic Agents/therapeutic use* ; Lipoproteins, HDL/blood* ; Liver/metabolism* ; Malondialdehyde/analysis* ; Peroxisome Proliferator-Activated Receptors/analysis* ; Rats ; Rats, Sprague-Dawley ; Saponins/therapeutic use* ; Superoxide Dismutase ; Triglycerides/blood* ; Trisaccharides/therapeutic use*

OBJECTIVETo comparatively study the effects of Rhubarbs from different regions on blood lipid and antioxi dation of hyperlipidemia rats.

METHODSMale rats were randomly divided into 9 groups ( n = 8) and fed with high-fat diet to replicate the hyperlipidemia model. Meanwhile, Rheum tanguticum was administrated intragastrically at two doses (3.0 g/kg and 1.0 g/kg), once a day for continuous 28 days. The effects of Rheum tanguticum planted in Gannan (RT-GN), Rheum tanguticum planted in Xinin (RT-XN) and Rheum plmatum planted in Lixian (RP-LX) were evaluated through detecting the parameters of blood lipids, blood viscosity and antioxidant system.

RESULTST-GN, RT-XN and RP-LX in the range of 1.0-3.0 g/kg could decrease the blood levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and malonaldehyde (MDA) in blood. Besides, they could reduce blood viscosity, increase high density lipoprotein (HDL) level and upregulate the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Interestingly, their effects on blood viscosity was obviously in a dose dependent manner. In addition, the effects of RT-GN on LDL, MDA and blood viscosity were not significantly different from those of RT-XN and better than those of RP-LX.

CONCLUSIONThe RT has better hypolipidemic effects than the RP, but RT-GN and RT-XN are not different from the above effects.

Animals ; Antioxidants ; metabolism ; Blood Viscosity ; Cholesterol ; blood ; Diet, High-Fat ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Glutathione Peroxidase ; metabolism ; Hyperlipidemias ; drug therapy ; Lipids ; blood ; Lipoproteins, HDL ; blood ; Lipoproteins, LDL ; blood ; Male ; Malondialdehyde ; blood ; Rats ; Rheum ; chemistry ; Superoxide Dismutase ; metabolism ; Triglycerides ; blood

The research aimed to investigate the therapeutic effects and mechanisms of Opuntia dillenii Haw polysaccharide (OPS) on atherosclerosis of rats. First atherosclerotic rat models were established by high-fat and high-calcium diet. Thirty days later, the rats were treated with low dosage of OPS (0.2 g x kg(-1) x d(-1)) or high dosage of OPS (0.4 g x kg(-1) x d(-1)) by intraperitoneal injection for 60 days continuously. At the end of treatment, thoracic aorta rings were prepared and vasorelaxation of rat thoracic aorta in different experiment groups were determined by using 620M multi wire myograph system in vitro. Blood and livers of rats were collected. Then plasma levels of total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) of rats were separately determined using whole automatic biochemical analyzer; protein level of hepatic apolipoprotein B (ApoB) and that of hepatic diglyceride acyltransferase (Dgat1) were measured by Western Blot technique. Results showed that the ability of rat thoracic aorta to relax decreased markedly in the model group compared with that in the normal group, and significant differences existed in vasorelaxation ratios induced by different concentrations of carbamylcholine chloride (Carb) between these two groups (P < 0.01). After OPS treatment, the ability of rat thoracic aorta to relax improved markedly, the vasorelaxation ratios induced by Carb at 5 and 10 μmol x L(-1) were respectively 0.34 ± 0.08 and 0.62 ± 0.15 in the group treated with low dosage of OPS, while the ratios induced by Carb at 1 and 5 μmol x L(-1) were respectively 0.54 ± 0.08 and 0.98 ± 0.02 in the group treated with high dosage of OPS, which were all significantly different with those in the model group (P < 0.01). Plasma contents of TC, TG and LDL reduced significantly by the treatments both with low and high dosages of OPS compared with those in the model group (P < 0.01). Protein level of hepatic ApoB and that of hepatic Dgat1 decreased significantly after the treatment with high dosage of OPS compared with those in the model group (P < 0.01). These results indicate that OPS can markedly improve the vasorelaxation of thoracic aorta of atherosclerotic rats and has significant anti-atherosclerotic effect; inhibiting the expression of ApoB and Dgat1 and thus decreasing the amounts of TC, LDL and TG serving as one of the molecular mechanisms of its antiatherosclerosis effect.
Animals ; Aorta, Thoracic ; drug effects ; Atherosclerosis ; drug therapy ; Cholesterol ; blood ; Lipoproteins, LDL ; blood ; Opuntia ; chemistry ; Phytotherapy ; Rats ; Triglycerides ; blood

OBJECTIVE: To measure retinol binding protein 4 (RBP4) levels in serum and bile and to analyze their relationship with insulin resistance, dyslipidemia or cholesterol saturation index (CSI).
 METHODS: A total of 60 patients with gallstone were divided into a diabetes group (n=30) and a control group (n=30). The concentrations of RBP4 in serum and bile were detected by enzyme-linked immunosorbent assay (ELISA). Enzyme colorimetric method was used to measure the concentration of biliary cholesterol, bile acid and phospholipid. Biliary CSI was calculated by Carey table. Partial correlation and multiple linear regression analysis were used to evaluate the correlation between the RBP4 levels in serum or bile and the above indexes.
 RESULTS: The RBP4 concentrations in serum and bile in the diabetes group were significantly elevated compared with those in the control group (both P<0.01). There was no significant difference in the serum total bile acid (TBA), serum triglyceride (TG), serum high-density lipoprotein (HDL), bile TBA, bile total cholesterol (TC) , bile phospholipids and bile CSI between the 2 groups (all P>0.05); but the serum TC, low density lipoprotein (LDL), fasting blood glucose (FBG), fasting insulin (FINS), and homeostasis model assessment for insulin resistance (HOMA-IR) in the diabetes group were significantly increased compared to those in the control group (all P<0.05). The partial correlation analysis, which was adjusted by age, showed that the bile RBP4 was positively correlated with body mass index (BMI), waist circumference (WC), FINS, FBG, TC, LDL and HOMA-IR (r=0.283, 0.405, 0.685, 0.667, 0.553, 0.424 and 0.735, respectively), and the serum RBP4 was also positively correlated with the WC, FINS, FBG, TC, LDL and HOMA-IR (r=0.317, 0.734, 0.609, 0.528, 0.386 and 0.751, respectively). Stepwise multivariate linear regression analysis suggested that the HOMA-IR, BMI and WC were independently correlated with the level of bile RBP4 (multiple regression equation: Ybile RBP4=2.372XHOMA-IR+0.420XBMI+0.178XWC-26.813), and the serum RBP4 level was correlated with the HOMA-IR and WC independently (multiple regression equation: Yserum RBP4=2.832XHOMA-IR +0.235XWC-20.128). Multiple regression equations showed that HOMA-IR was the strongest correlation factor with RBP4.
 CONCLUSION RBP4 concentrations in serum and bile in the diabetes group are significantly higher than those in the control group. HOMA-IR, BMI and WC are independently correlated with the level of bile RBP4. HOMA-IR and WC are independently correlated with the serum RBP4 level. HOMA-IR is the strongest correlation factor with RBP4. RBP4 might play an important role in the course of gallstone formation in Type 2 diabetes mellitus.
Bile ; chemistry ; Bile Acids and Salts ; blood ; Blood Glucose ; chemistry ; Body Mass Index ; Cholesterol ; chemistry ; Diabetes Mellitus, Type 2 ; complications ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Gallstones ; complications ; Humans ; Insulin ; blood ; Insulin Resistance ; Lipoproteins, HDL ; blood ; Lipoproteins, LDL ; blood ; Phospholipids ; chemistry ; Retinol-Binding Proteins, Plasma ; metabolism ; Triglycerides ; blood ; Waist Circumference

OBJECTIVETo investigate the effect of Antrodia cinnamomea on gene expression related to aortal endothelial injury of rats with hyperlipidemia.

METHODFifty SD rats were randomly divided into five groups: the normal control group (NG), the model group (MG), the antrodia cinnamomea groups of low, middle and high doses (AC-LG, AC-MG, AC-HG, 250, 500, 1 000 mg x kg(-1)). The rats were fed with high-fat diets to establish the hyperlipidemia model. After the drug administration for 10 weeks, their serum lipid, SOD, MDA and ox-LDL, LOX-1, P38 MAPK and NF-kappaB mRNA and protein expression were respectively determined, and the aortal endothelial injury was observed under electron microscope.

RESULTIn the model group, the contents of TC, TG and LDL-C significant increased (P < 0.01), whereas the content of HDL-C significant decreased (P < 0.01). Compared with the model group, both the AC-M group and the AC-H group showed reduction in endothelial injury and significant decrease in the content of TC, TG and LDL-C (P < 0.05 or P < 0.01). The content of HDL-C increased, but with no significant difference. SOD activity in serum remarkably increased (P < 0.05 or P < 0.01), MDA and ox-LDL levels dramatically decreased (P < 0.05 or P < 0.01).

CONCLUSIONA. cinnamomea can alleviate endothelial lipid injury by inhibiting the expressions of LOX-1, P38MAPK and NF-kappaB in aorta and better protect aortal endothelial cells from oxidative lipid injury.

Animals ; Antrodia ; chemistry ; Aorta ; drug effects ; metabolism ; ultrastructure ; Atherosclerosis ; blood ; genetics ; prevention & control ; Biological Products ; pharmacology ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Endothelium, Vascular ; drug effects ; metabolism ; pathology ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; drug effects ; Hyperlipidemias ; blood ; genetics ; prevention & control ; Lipoproteins, LDL ; blood ; Male ; Malondialdehyde ; blood ; Microscopy, Electron ; NF-kappa B ; blood ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Scavenger Receptors, Class E ; blood ; genetics ; metabolism ; Superoxide Dismutase ; blood ; Triglycerides ; blood ; p38 Mitogen-Activated Protein Kinases ; blood ; genetics ; metabolism

The effects of effective part group on hyperlipidemia in animal were studied. The SD rats, hamsters and Kunming mouse were divided into blank group, model group. The positive control group and test group were fed with normal diet, blank and other groups were fed with high fat diet (mouse only a single intraperitoneal injection of egg yolk ). The corresponding concentration of solvent, simvastatin, effective part group of emulsion were given gavage once daily. The animal serum total cholesterol (TC) , triglyceride (TG) , low density lipoprotein (LDL) , high density lipoprotein (HDL) and liver TC, TG contents were determined to observe the effects of the effective fractions on blood lipid regulating function. Comparing with control group, the animial hyperlipidemia models of the SD rat (TC increase), mouse (TC, TG, LDL increase), hamsters ( TC, TG, LDL increase, HDL decrease) (P <0. 05, P < 0. 001) were successfully established. Piper longum effective part group could decrease the serum TC, TG, LDL (P <0.05, P < 0. 001) and liver TC, TG content, and elevate serum HDL levels (P <0.05, P <0.001). The golden hamster is ideal for hyperlipidemia model.
Alkaloids ; pharmacology ; therapeutic use ; Animals ; Benzodioxoles ; pharmacology ; therapeutic use ; Cholesterol ; blood ; metabolism ; Cricetinae ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Hyperlipidemias ; blood ; drug therapy ; metabolism ; Lipid Metabolism ; drug effects ; Lipoproteins, HDL ; blood ; metabolism ; Lipoproteins, LDL ; blood ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Mice ; Piper ; chemistry ; Piperidines ; pharmacology ; therapeutic use ; Polyunsaturated Alkamides ; pharmacology ; therapeutic use ; Rats ; Triglycerides ; blood ; metabolism

OBJECTIVE: To study the correlation between the serum levels of nitrogen oxide (NO) and oxidized low density lipoprotein (oxLDL) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). METHOD: NO and oxLDL levels were measured in 60 OSAHS patients and 26 healthy subjects. OSAHS patients were divided into mild, moderate and severe groups according to AHI. RESULT: NO levels in the moderate and sever OSAHS groups was significantly lower than that in the control group, but the levels of oxLDL was increased compared with the control group. (P < 0.05). The serum levels of NO was negatively correlated with AHI (P < 0.01) and positively correlated with the lowest SaO2 (P < 0.01), the serum levels of oxLDL was positively correlated with AHI (P < 0.01) and negatively correlated with the lowest SaO2 (P < 0.01), NO levels showed negative correlations with oxLDL levels (P < 0.01). CONCLUSION The serum level of NO is reduced in response to the increase of AHI and the acceleration of hypoxia, which indicated that there is a correlation between vascular endothelial dysfunction and the severity of hypoxia. The decrease of the level of NO and the increase of the oxLDL can promote the formation of atherosclerosis, which increased the incidence of cardiocerebrovascular disease in patients with OSAHS.
Adult ; Case-Control Studies ; Female ; Humans ; Lipoproteins, LDL ; blood ; Male ; Middle Aged ; Nitric Oxide ; blood ; Serum ; chemistry ; Sleep Apnea, Obstructive ; blood ; physiopathology

The selective removal of low density lipoprotein (LDL) and fibrinogen (Fib) by degraded carrageenan was studied by the present authors. Degraded carrageenan was prepared by acid with carrageenan as the main material. The effects of acid conditions on the molecular weight were investigated, and the proper reaction conditions were ascertained. The results of infrared spectrometry indicated that the degraded carrageenan is a heparin-like polysaccharide. Then the selective removal of LDL/Fibrinogen by degraded carrageenan was studied. When molecular weight was about 10,000, pH was 5.10 and the concentration of degraded carrageenan was 800 mg/L, the average reduction percentages were 60.0% for total cholesterol(TC), 79.4% for LDL and very low-density lipoprotein (VLDL), and 93.8% for fibrinogen. There were no significant changes with relation to the level of high-density lipoprotein (HDL) and total protein (TP). So, degraded carrageenan was shown to be of good selectivity on plasma LDL/Fibrinogen apheresis.
Carrageenan ; chemistry ; Fibrinogen ; analysis ; isolation & purification ; Humans ; Hyperlipidemias ; blood ; Lipoproteins, LDL ; blood ; isolation & purification

OBJECTIVETo investigate the hypocholesterolemic activity of red yeast rice (RYR) and its underlying mechanism.

METHODSThree groups of hamsters were fed either the control diet or one of the two experimental diets containing by weight 0.1% RYR (0.1RYR) or 0.3% RYR (0.3RYR). Blood (0.5 mL) was collected from the retro-orbital sinus into a heparinized capillary tube at the end of week 0, 3, and 6. Plasma lipoproteins were measured using enzymatic kits, while fecal neutral and acidic sterols were quantified using a gas-liquid chromatography.

RESULTSPlasma total cholesterol was reduced by 12% in 0.1RYR group and by 18% in 0.3RYR group compared with the control value. Similarly, plasma triacylglycerol was decreased by 11% in 0.1RYR group and by 24% in 0.3RYR group. Western blotting analysis demonstrated that RYR had no effect on sterol regulatory element binding protein 2, liver X receptor, 3-hydroxy-3-methylglutary-CoA reductase, LDL receptor, and cholesterol-7alpha-hydroxylase. HPLC analysis confirmed that RYR contained 0.88% monacolin K. It was recently found that RYR supplementation increased excretion of fecal acidic sterols by 3-4 folds compared with the control value.

CONCLUSIONHypocholesterolemic activity of RYR is mediated at least partially by enhancement of acidic sterol excretion.

Animals ; Bile Acids and Salts ; secretion ; Biological Products ; pharmacology ; Blotting, Western ; Body Weight ; drug effects ; Cholesterol ; metabolism ; Cholesterol 7-alpha-Hydroxylase ; metabolism ; Cricetinae ; Dietary Supplements ; Feces ; chemistry ; Feeding Behavior ; drug effects ; Hydroxymethylglutaryl CoA Reductases ; metabolism ; Lipoproteins ; blood ; Liver ; enzymology ; Liver X Receptors ; Naphthalenes ; analysis ; Organ Size ; drug effects ; Orphan Nuclear Receptors ; metabolism ; Receptors, LDL ; metabolism ; Sterol Regulatory Element Binding Protein 2 ; metabolism ; Weight Gain ; drug effects