BACKGROUND: Endothelial dysfunction, the initial pathogenic factor in atherosclerosis, can be alleviated via transient limb ischemia. We observed the effects of regular transient limb ischemia (RTLI) on atherosclerosis in hypercholesterolemic rabbits. METHODS: Twenty-eight rabbits were randomized to control, cholesterol, sham, ischemia groups (n = 7 each) between October 2010 and March 2011. They were fed a normal diet in the control group and hypercholesterolemic diet in other groups for 12 weeks. Six cycles of RTLI were performed once per day on the ischemia group. Serum samples were prepared to measure the total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) before the experiment (W0), at the end of weeks 4, 8, 12 (W4, W8, W12). The whole aorta was harvested at W12 and stained using Sudan IV to identify the plaque. The plaque area was measured using Image J. Results were analyzed by analysis of variance or rank sum test. RESULTS: Concentrations of TC in the cholesterol group were higher than those in the control group at W4 (29.60 [23.75, 39.30] vs. 1.00 [0.80, 1.55], Z = -2.745, P = 0.006), W8 (41.78 [28.08, 47.37] vs. 0.35 [0.10, 0.68], Z = -2.739, P = 0.006), W12 (48.32 [40.04, 48.95] vs. 0.61 [0.50, 0.86], Z = -2.739, P = 0.006). Similar results were obtained for HDL-C and LDL-C. Serum concentrations of TC, HDL-C, and LDL-C in the hypercholesterolemic groups had no differences (all P > 0.05). The percentage of plaque area in the cholesterol group was higher than that in the control group (47.22 ± 23.89% vs. 0, Z = -2.986, P = 0.003). Square root of the percentage of plaque area was smaller in the ischemia group than that in the cholesterol (0.44 ± 0.13 vs. 0.67 ± 0.18, P = 0.014) or sham groups (0.44 ± 0.13 vs. 0.61 ± 0.12, P = 0.049). CONCLUSION In hypercholesterolemic rabbits, RTLI might prevent atherosclerosis progression by reducing the percentage of plaque area.
Animals ; Atherosclerosis ; blood ; prevention & control ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Extremities ; pathology ; Hypercholesterolemia ; blood ; Ischemic Attack, Transient ; blood ; Ischemic Postconditioning ; methods ; Male ; Rabbits ; Triglycerides ; blood

Lipid-lowering and antioxidant activities of a hydroalcoholic extract of Cyperus scariosus Linn. root (HCS) were evaluated in guinea pigs fed with a high cholesterol diet. Serum lipid profile (total cholesterol, triglycerides, LDL-C, VLDL-C, and HDL-C), atherogenic indices and serum enzymes (ALT, AST, ALP, LDH, and CK-MB) were performed in each group at 0 days and at the end of 60 days. Histological study of liver and kidney was done in groups 1, 2, 5, 6 and 7. The total phenolic and flavonoid content in HCS and its antioxidant activity were evaluated by the DPPH assay. Both doses of HCS decreased serum lipid profile and atherogenic indices (P < 0.05). HCS has lipid lowering, immunosuppressive and antioxidant properties, and mays have value in atherosclerosis prevention. The higher dose of HCS also reduced serum AST, ALP, and LDH levels and rosuvastatin increased AST and ALP levels (P < 0.05). Histology of the liver showed decreased lipid accumulation and improvement in hepatocytes in HCS-treated animals. The antioxidant activity of HCS may be responsible for its lipid lowering and cytoprotective action. HCS had significant lipid lowering and antioxidant activity, which; may be due to the phenolic compounds. HCS may be a safe and cost effective alternative to current statin therapy for patients with dyslipidaemia.
Animals ; Cyperus ; Female ; Guinea Pigs ; Hypercholesterolemia ; drug therapy ; Hypolipidemic Agents ; pharmacology ; therapeutic use ; Kidney ; pathology ; Liver ; pathology ; Male ; Mice ; Plant Extracts ; pharmacology ; therapeutic use ; Plant Roots ; chemistry

OBJECTIVETo study the effect of Lycium ruthenicum anthocyanins on atherosclerosis (AS) in mice.

METHODNormal mice were taken as the control group, and hyperlipemia mice were divided into the model group, Lycium ruthenicum anthocyanins low, medium and high dose groups, and the simvastatin drug control group. After the oral administration, blood lipid indicators were detected by enzymatic analysis. The histomorphological changes in aortas, hearts and livers were observed, and liver-related indicators were determined by using hematoxylin-eosin (HE) staining.

RESULTCompared with the high-fat group, L. ruthenicum anthocyanins low, medium and high dose groups showed significant decrease in total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and atherosclerotic index (AI) (P < 0.05). However, high-density lipoprotein cholesterol (HDL-C) level showed a trend of higher than the model group. Liver's total antioxidant capacity (T-AOC), Glutathione peroxidase (GSH-PX), lipoprotein lipase (LPL) were significantly increased (P < 0.05), malondialdehyde (MDA) was markedly decreased (P < 0.01); the percentage of aortic plaque area of each anthocyanins dose group in the total area was significantly lower than the model group (P < 0.05); severity of aorta, heart and liver were significantly lighter than the high-fat group. But the media dose group was similar with the simvastatin group.

CONCLUSIONL. ruthenicum anthocyanins can interfere the formation of AS, while lowering blood lipid levels in mice.

Animals ; Anthocyanins ; therapeutic use ; Atherosclerosis ; prevention & control ; Body Weight ; drug effects ; Glutathione Peroxidase ; metabolism ; Hypercholesterolemia ; blood ; drug therapy ; pathology ; Lipids ; blood ; Liver ; pathology ; Lycium ; chemistry ; Male ; Mice ; Phytotherapy

OBJECTIVETo study the clinical features and ABCG5/ABCG8 gene mutations of three pedigrees of phytosterolemia presented with macrothrombocytopenia and hemolysis.

METHODSErythrocyte and platelet morphology were examined under light microscope. Plasma sterol levels were measured by high pressure/performance liquid chromatography method. All of ABCG5 and ABCG8 exons and intron-exon boundaries were directly sequenced to identify mutations, the corresponding gene mutation sites of three families members and healthy individuals were detected.

RESULTSAll the patients presented macrothrombocytopenia, hemolysis, splenomegaly and xanthomas. The blood smears showed large platelets, some as large as erythrocytes, and abnormal erythrocyte shapes, such as stomatocytes. Plasma concentrations of phytosterols, especially sitosterol were markedly elevated (30 fold) in the affected patients. Four mutations were identified in these three pedigrees, ABCG5 C20896T (R446X) and A20883G, ABCG8 del43683-43724 and del1938C-1939G/ins1938T. The latter three were novel mutations reported for the first time.

CONCLUSIONSPhytosterolemia associated with macrothrombocytopenia and hemolysis is a new subtype of this disease. Plasma phytosterols and related gene analysis should be performed when ever an unexplained macrothrombocytopenia, especially combined with haemolysis or/and stomatocytosis.

ATP Binding Cassette Transporter, Sub-Family G, Member 5 ; ATP Binding Cassette Transporter, Sub-Family G, Member 8 ; ATP-Binding Cassette Transporters ; genetics ; Adult ; Blood Platelets ; cytology ; DNA Mutational Analysis ; Erythrocytes, Abnormal ; Female ; Hemolysis ; genetics ; Humans ; Hypercholesterolemia ; genetics ; pathology ; Intestinal Diseases ; genetics ; pathology ; Lipid Metabolism, Inborn Errors ; genetics ; pathology ; Lipoproteins ; genetics ; Male ; Middle Aged ; Mutation ; Pedigree ; Phytosterols ; adverse effects ; blood ; genetics ; Platelet Count ; Thrombocytopenia ; genetics ; pathology

OBJECTIVETo establish abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model fed with high fat diet. And then to investigate the pathological characteristics of this quail model.

METHODSThirty Longcheng quails were randomly divided into two groups: control group and model group (n=15). The control group quails were fed with normal diet and model group quails were fed with high fat diet for 14 days. After a 12-hour overnight fast, liver and abdominal fat at euthanasia as well as serum were collected. The levels of serum uric acid, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride, free fatty acid (FFA), and blood glucose were assayed. The activity changes of adenosine deaminase (ADA), xanthine oxidase (XOD), lipoprotein lipase (LPL), hepatic lipase (HL), and fatty acid synthetase (FAS) were analyzed.

RESULTSCompared with control group, the abdominal fat content (0.74+/-0.63 vs. 1.36+/-0.65 g, P<0.05) and abdominal fat index (0.44%+/-0.30% vs. 0.85%+/-0.30%, P<0.01) as well as live lipid index (3.61%+/-0.65% vs. 11.33%+/-2.14%, P<0.01) in model group significantly increased; the levels of serum uric acid (210.61+/-94.76 vs. 304.25+/-141.94 micromol/L, P<0.05), total cholesterol (4.20+/-0.51 vs. 20.10+/-11.25 mmol/L, P<0.01), LDL-C (1.16+/-0.29 vs. 10.78+/-6.48 mmol/L, P<0.01), and FFA (0.39+/-0.14 vs. 0.55+/-0.15 mmol/L, P<0.01) in model group significantly increased; HDL-C (5.85+/-0.95 vs. 4.14+/-2.03 mmol/L, P<0.05) significantly decreased; the levels of triglyceride and blood glucose had no significant changes (P>0.05); the activities of ADA (9.71+/-3.05 vs. 17.19+/-5.10 U/ml, P<0.01) and XOD (10.58+/-6.88 vs. 19.22+/-9.44 U/L, P<0.01) in model group significantly increased; and FAS, LPL, HL had no significant changes (P>0.05).

CONCLUSIONSHigh fat diet can induce abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model. The changes of uric acid and lipid metabolic enzyme activities may be the pathological mechanism of abdominal fat accumulation with hyperuricemia and hypercholesterolemia.

Abdominal Fat ; pathology ; Animals ; Body Weight ; Coturnix ; Dietary Fats ; administration & dosage ; Disease Models, Animal ; Hypercholesterolemia ; etiology ; metabolism ; pathology ; Hyperuricemia ; etiology ; metabolism ; pathology ; Lipid Metabolism ; Lipids ; blood ; Liver ; metabolism ; Male ; Uric Acid ; blood

Cajanus cajan L. is a natural plant, which contains a lot of potential active components. In the present study, we identified the effects of the stilbene extract from Cajanus cajan L. (sECC) on hepatic cholesterol metabolism in diet-induced (for 4 weeks) hyperlipidemic Kunming mice. All experimental mice were divided into 5 groups: control group, high lipid model group, sECC-treated with 200 or 100 mg kg(-1), and simvastatin (Sim, 12 mg kg(-1)) treated group. The mice were fed with fat and cholesterol-enriched chow except control mice that were fed with standard diet. The effects of sECC were investigated by monitoring serum and liver lipid profile (i. e. cholesterol homeostasis) in mice. To further explore the mechanism of sECC, hepatic cholesterol 7alpha-hydroxylase (CYP7A1) and low density lipoprotein (LDL) receptor expressions in cholesterol homeostasis were analyzed by reverse transcription PCR. After 4 weeks pretreatment, the mice in the high lipid model group showed markedly higher serum and hepatic lipid contents than control group (P< 0.01). Compared with high lipid model group, the increased serum and hepatic lipid contents were markedly attenuated by sECC (200 mg kg(-1)), the serum and hepatic total cholesterol were reduced by 31.5% and 22.7% (P<0.05), respectively. The triglyceride contents of serum and liver were also lowered by 23.0% and 14.4%, respectively. At the same times, serum LDL cholesterol decreased by 53.0% (P<0.01). The mRNA expressions of hepatic CYP7A1 and LDL-receptor were significantly enhanced in the mice administered with sECC (200 mg kg(-1)), whereas those expressions were suppressed by the fat and cholesterol-enriched diet. These data indicate that sECC reduces the atherogenic properties of dietary cholesterol in mice. It is indicated that expression enhancement of hepatic LDL-receptor and cholesterol 7alpha-hydroxylase may be responsible for the hypercholesterolemic effect.
Animals ; Anticholesteremic Agents ; isolation & purification ; pharmacology ; Body Weight ; drug effects ; Cajanus ; chemistry ; Cholesterol ; blood ; metabolism ; Cholesterol 7-alpha-Hydroxylase ; biosynthesis ; genetics ; Cholesterol, LDL ; blood ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Gene Expression Regulation ; Hypercholesterolemia ; blood ; genetics ; metabolism ; pathology ; Liver ; metabolism ; pathology ; Male ; Mice ; Organ Size ; drug effects ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry ; RNA, Messenger ; metabolism ; Receptors, LDL ; biosynthesis ; genetics ; Stilbenes ; isolation & purification ; pharmacology ; Triglycerides ; blood ; metabolism

In our previous study, two point mutants of apolipoprotein A-I, designated V156K and A158E, revealed peculiar characteristics in their lipid-free and lipid-bound states. In order to determine the putative therapeutic potential of these mutants, several in vitro and in vivo evaluations were conducted. In the lipid-free state, V156K showed more profound antioxidant activity against LDL oxidation than did the wildtype (WT) or A158E variants in an in vitro assay. In the lipid-bound state, V156K-rHDL showed an enhanced cholesterol delivery activity to HepG2 cells in a time-dependent manner, as compared to WT-rHDL, A158E-rHDL, and R173C-rHDL. We assessed the physiological activities of the mutants in circulation, using hypercholesterolemic mice (C57BL6/J). Palmitoyloleoyl phosphatidylcholine (POPC)-rHDL preparations containing each of the apoA-I variants were injected into the mice at a dosage of 30 mg of apoA-I/kg of body weight. Forty eight hours after injection, the sera of the V156K-rHDL injected group showed the most potent antioxidant abilities in the ferric acid removal assay. The V156K-rHDL- or R173C-rHDL-injected mice showed no atherosclerotic lesions and manifested striking increases in their serum apo-E levels, as compared to the mice injected with WT-rHDL or A158E-rHDL. In conclusion, V156K-rHDL exhibited the most pronounced antioxidant activity and anti-atherosclerotic activity, both in vitro and in vivo. These results support the notion that HDL-therapy may prove beneficial due to its capacity to induce accelerated cholesterol excretion, as well as its enhanced antioxidant and anti-inflammatory effects and lesion regression effect.
Amino Acids/*genetics ; Animals ; Antioxidants/*metabolism ; Apolipoprotein A-I/*genetics ; Atherosclerosis/*pathology ; Biological Transport/drug effects ; Cell Line, Tumor ; Cholesterol/metabolism ; Copper/pharmacology ; Humans ; Hypercholesterolemia/chemically induced/*pathology ; Lipoproteins, HDL/blood ; Lipoproteins, LDL/blood ; Male ; Mice ; Mice, Inbred C57BL ; Oxidation-Reduction/drug effects ; Point Mutation/*genetics ; Recombinant Proteins/blood

OBJECTIVETo investigate the effects of Danshen on number and activity of endothelial progenitor cells (EPCs) of patients with Hypercholesterolemia.

METHOD24 patients with Hypercholesterolemia were randomLy divided into 2 groups: control group (n = 12), and treatment group (n = 12, receiving Composite Denshen Pilulae, 10# tid for 2 weeks). after 2 weeks, 20 mL peripheral blood was obtained from each patient, Mononuclear fraction of human peripheral blood was obtained by density gradient centrifugation, plated on fibronectin coated culture dishes. The cells were identified by immunohistochemistry and flow cytometry and tested the ability to intake ac-LDL. Cell clusters were viewed with an inverted microscope, fluorescence-activated cell sorting (FACS) analysis of PE-CD34 and FITC-AC133 was performed to detect number of EPCs, EPC proliferation and migration were assayed with MTT assay, modified Boyden chamber assay. EPCs adhesion ability assay was performed by replating cells on fibronectin-coated dishes, and then counting adherent cells.

RESULTNumbers of EPCs (10(3) cells per 1 mL peripheral blood) of treatment group was higher than control group (7.20 +/- 1.29 vs 6.88 +/- 1.00). Compared with group control, numbers of clusters (per 40 power microscopic field), adhesive EPCs (per 400 power microscopic field) and migratory EPCs (per 200 power microscopic field) of treatment group were significantly increased (4.47 +/- 0.94 vs 3.38 +/- 0.57, P <0.01, 11.81 +/- 2.29 vs 10.03 +/- 1.32, P <0.05 and 15.75 +/- 2.27 vs 11.95 +/- 1.28, P <0.01, respectively), while OD vallue of treatment group were significantly increased too (0.27 +/- 0.04 vs 0. 20 +/- 0.03, P < 0.01).

CONCLUSIONDanshen can significantly enhance EPCs functional activity of patients with Hypercholesterolemia.

Antigens, CD34 ; analysis ; Cell Adhesion ; drug effects ; Cell Count ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Endothelial Cells ; drug effects ; metabolism ; pathology ; Female ; Flow Cytometry ; Humans ; Hypercholesterolemia ; blood ; pathology ; Immunohistochemistry ; Male ; Plants, Medicinal ; chemistry ; Salvia miltiorrhiza ; chemistry ; Stem Cells ; drug effects ; metabolism ; pathology

OBJECTIVETo study the influence of beta-amyloid protein (Abeta) and cholesterol on the pathological changes of Alzheimer's disease (AD) and on the expression of nicotinic acetylcholine receptor (nAChR) subunits in the brains of rats.

METHODThe rats were treated by intracerebroventricular injection of Abeta1-42 and fed with a diet containing 5% cholesterol to establish animal model of AD. The pathological changes, learning and memory, and expression of nAChRs of rats were analyzed by Bieoschowsky staining, immunohistochemistry, water-labyrinth, Western blot, and RT-PCR.

RESULTSAbeta intracerebroventricular injection induced Abeta deposition in rat brains and high-cholesterol diet resulted in hypercholesterolemia in the animals. Injection of Abeta caused a reduction of learning and memory of rats and modifications of the expression of nAChRs. Cholesterol enhanced these effects of Abeta on neuropathology and expression of nAChRs.

CONCLUSIONSAbeta can induce marked neuropathological changes, influence the learning and study ability, and modify the expression of nAChRs. Cholesterol can enhance the neurotoxicity of Abeta.

Alzheimer Disease ; chemically induced ; metabolism ; pathology ; physiopathology ; Amyloid beta-Peptides ; metabolism ; Animals ; Cerebral Cortex ; metabolism ; pathology ; Cholesterol ; blood ; Drug Synergism ; Female ; Hypercholesterolemia ; blood ; Learning ; drug effects ; Male ; Peptide Fragments ; metabolism ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Receptors, Nicotinic ; biosynthesis ; genetics

OBJECTIVETo study the effects of enhanced external counterpulsation (EECP) on the vascular morphology, and endothelial function using experimentally induced hypercholesterolemic pigs.

METHODSThirty five male pigs were randomly divided into three groups: 7 normal control animals, 11 hypercholesterolemic animals, and 17 hypercholesterolemic animals receiving EECP. Serum cholesterol was measured. The coronary arteries and aortas were sampled for histopathologic and ultrastructural examination. The NF-kappaB protein expression of porcine coronary arteries was investigated by immunofluorescence.

RESULTSCompared with the normal controls, serum cholesterol levels were significantly higher in the hypercholesterolemic animals with or without EECP. The plaque/intimal area ratio of the aorta decreased significantly in animals receiving EECP [(3.33 +/- 2.40)%, versus (12.03 +/- 7.12)% in those without EECP, P < 0.05]. Lipid deposition, endothelial damage and proliferation of smooth muscle cells were less severe in animals receiving EECP than those not. Moreover, activation and expression of NF-kappaB also decreased significantly (P < 0.05) in animals receiving EECP.

CONCLUSIONSEECP improves the morphology and function of vascular endothelium, and retards the development and progression of atherosclerosis, likely through the inhibition of NF-kappaB signaling pathway.

Animals ; Aorta, Abdominal ; metabolism ; pathology ; ultrastructure ; Atherosclerosis ; blood ; metabolism ; pathology ; Cholesterol ; blood ; Coronary Vessels ; metabolism ; pathology ; ultrastructure ; Counterpulsation ; methods ; Endothelial Cells ; metabolism ; pathology ; Hypercholesterolemia ; blood ; metabolism ; pathology ; Lipoproteins, LDL ; blood ; Male ; Microscopy, Confocal ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Muscle, Smooth, Vascular ; metabolism ; pathology ; NF-kappa B ; metabolism ; Random Allocation ; Swine