PURPOSE: Appropriate animal models of atherosclerotic plaque are crucial to investigating the pathophysiology of atherosclerosis, as well as for the evaluation of the efficacy and safety of vascular devices. We aimed to develop a novel animal model that would be suitable for the study of advanced atherosclerotic lesions in vivo. MATERIALS AND METHODS: Atherosclerotic plaque was induced in 24 iliac arteries from 12 rabbits by combining a high cholesterol diet, endothelial denudation, and injection into the vessel wall with either saline (n=5), olive oil (n=6), or inflammatory proteins [n=13, high-mobility group protein B1 (HMGB1) n=8 and tumor necrosis factor (TNF)-α n=5] using a Cricket™ Micro-infusion catheter. Optical coherence tomography (OCT) was performed to detect plaque characteristics after 4 weeks, and all tissues were harvested for histological evaluation. RESULTS: Advanced plaque was more frequently observed in the group injected with inflammatory proteins. Macrophage infiltration was present to a higher degree in the HMGB1 and TNF-α groups, compared to the oil or saline group (82.1±5.1% and 94.6±2.2% compared to 49.6±14.0% and 46.5±9.6%, p-value<0.001), using RAM11 antibody staining. On OCT, lipid rich plaques were more frequently detected in the inflammatory protein group [saline group: 2/5 (40%), oil group: 3/5 (50%), HMGB1 group: 6/8 (75%), and TNF-α group: 5/5 (100%)]. CONCLUSION: These data indicate that this rabbit model of atherosclerotic lesion formation via direct injection of pro-inflammatory proteins into the vessel wall is useful for in vivo studies investigating atherosclerosis.
Animals ; Cholesterol, Dietary/administration & dosage ; *Disease Models, Animal ; Endothelium/surgery ; HMGB1 Protein/*adverse effects ; Iliac Artery/diagnostic imaging/pathology/surgery ; Injections, Intra-Arterial ; Macrophages ; Male ; Olive Oil/adverse effects ; Plaque, Atherosclerotic/*chemically induced/diagnostic imaging/pathology ; Rabbits ; Sodium Chloride/adverse effects ; Tomography, Optical Coherence ; Tumor Necrosis Factor-alpha/*adverse effects

PURPOSE: Clinical trials have studied the use of soy protein for treating type 2 diabetes (T2D) and metabolic syndrome (MS). The purpose of this study was to outline evidence on the effects of soy protein supplementation on clinical indices in T2D and MS subjects by performing a meta-analysis of randomized controlled trials (RCTs). MATERIALS AND METHODS: We searched PubMed, EMBASE, and Cochrane databases up to March 2015 for RCTs. Pooled estimates and 95% confidence intervals (CIs) were calculated by the fixed-and-random-effects model. A total of eleven studies with eleven clinical variables met the inclusion criteria. RESULTS: The meta-analysis showed that fasting plasma glucose (FPG) [weighted mean difference (WMD), -0.207; 95% CI, -0.374 to -0.040; p=0.015], fasting serum insulin (FSI) (WMD, -0.292; 95% CI, -0.496 to -0.088; p=0.005), homeostasis model of assessment for insulin resistance index (HOMA-IR) (WMD, -0.346; 95% CI, -0.570 to -0.123; p=0.002), diastolic blood pressure (DBP) (WMD, -0.230; 95% CI, -0.441 to -0.019; p=0.033), low-density lipoprotein cholesterol (LDL-C) (WMD, -0.304; 95% CI, -0.461 to -0.148; p=0.000), total cholesterol (TC) (WMD, -0.386; 95% CI, -0.548 to -0.225; p=0.000), and C-reactive protein (CRP) (WMD, -0.510; 95% CI, -0.722 to -0.299; p=0.000) are significant reduced with soy protein supplementation, compared with a placebo control group, in T2D and MS patients. Furthermore, soy protein supplementation for longer duration (≥6 mo) significantly reduced FPG, LDL-C, and CRP, while that for a shorter duration (<6 mo) significantly reduced FSI and HOMA-IR. CONCLUSION: Soy protein supplementation could be beneficial for FPG, FSI, HOMA-IR, DBP, LDL-C, TC, and CRP control in plasma.
Aged ; Blood Glucose/*metabolism ; Blood Pressure ; C-Reactive Protein/metabolism ; Cardiovascular Diseases/prevention & control ; Cholesterol/blood ; Diabetes Mellitus, Type 2/blood/*therapy ; *Dietary Supplements ; Humans ; Lipids/blood ; Metabolic Syndrome X/*blood/prevention & control ; Randomized Controlled Trials as Topic ; Soybean Proteins/*administration & dosage ; *Soybeans

OBJECTIVE: To explore the expression of CyPA and CD147 in rabbit models of vulnerable carotid atherosclerotic plaque and the therapeutic effect of atorvastatin.
 METHODS: Twenty-four male New Zealand rabbits were randomly divided into 3 groups. Eight rabbits were served as a normal diet group (Group A), and the remaining 16 rabbits underwent balloon-induced endothelial injury in the right carotid artery and thereafter were fed on high-cholesterol diet (1% cholesterol) for 12 weeks, then they were divided into 2 groups: a AS group (Group B), an atorvastatin group [Group C, 2.5 mg/(kg.d)]. 4 weeks later, plaque disrupture was triggered by China Russell's viper venom and histamine. Serum levels of TC, TG, LDL-C and HDL-C were measured at different timepoint. The damaged carotid arteries were collected to undergo pathological examination. The macrophage, expression of CyPA and CD147 were detected by immuno-histochemical analysis, and the mRNA levels of CyPA and CD147 were examined by reverse transcription polymerase chain reaction (RT-PCR).
 RESULTS: Compared with the Group A, the serum levels of TC and LDL-c in the Group B and Group C were significantly increased (all P<0.01). Compared with the Group B, the serum levels of TC and LDL-c in the Group C were reduced significantly after atorvastatin intervention for 4 weeks (all P<0.01). The plaques disruption and thrombosis occurred in 4 out of the 6 rabbits in the Group B, while only 1 rabbit demonstrated plaques disruption and thrombosis in the Group C. Compared with the Group B, the levels of CyPA, CD147 and macrophage in carotid atherosclerotic plaque in the Group C were decreased significantly (all P<0.01).
 CONCLUSION The up-regulation of CyPA and CD147 may be involved in pathogenesis of vulnerable carotid atherosclerotic plaque. Atorvastatin could stabilize the plaque through inhibiting the CyPA and CD147 expression.
Animals ; Atorvastatin ; pharmacology ; Basigin ; metabolism ; Carotid Artery, Common ; pathology ; Cholesterol ; blood ; Cholesterol, Dietary ; administration & dosage ; Cyclophilin A ; metabolism ; Macrophages ; cytology ; Male ; Plaque, Atherosclerotic ; drug therapy ; metabolism ; Rabbits ; Random Allocation ; Thrombosis ; pathology ; Triglycerides ; blood

OBJECTIVETo detect the optimal predictors of vulnerable atherosclerotic plaques.

METHODSForty New Zealand white rabbits underwent balloon-induced abdominal aortic wall injury and were fed a high cholesterol and saturated fat diet containing 1% cholesterol for 8 weeks. Rabbits were then randomly divided into two groups: group A (n = 20, the aortic segments rich in plaques were incubated transluminally with recombinant adenovirus carrying p53) and group B [n = 20, incubated transluminally with β galactosidase (LacZ) genes]. Two weeks later, rabbits underwent pharmacological triggering with injection of Chinese Russell's viper venom (CRVV) and histamine. Before pharmacologically triggering, concentrations of hs-CRP, sVCAM-1 and sICAM-1 were measured by means of Enzyme-linked-immunosorbent assay (ELISA). Fibrinogen was analyzed by nephelometer. Ultrasound imaging, accuracy densitometry (AD) examination and intravascular ultrasound (IVUS) were performed to analyze the in vivo features of vulnerable plaques. Logistic regression was used to detect the predictors for vulnerable plaques.

RESULTSThe ratio of plaque rupture after pharmacological triggering was significantly higher in group A (89.5%, 17/19) than in group B (22.2%, 4/18). Serum hs-CRP level was significantly higher in plaque rupture group than in non-rupture group before pharmacological triggering (P < 0.05). In the meantime, parameters derived from ultrasound imaging [intima-media thickness (IMT) and peak velocity (VP), values of accuracy densitometry], measurements of IVUS [external elastic membrance area (EEMA), plaque area (PA), plaque burden (PB), eccentric index (EI) and remodeling index (RI)] were significantly larger in plaque rupture group than in non-rupture group. Logistic regression showed that EI (OR = 26.917), PA (OR = 19.301), sVCAM-1 (OR = 1.339) and AII-c% (OR = 0.458) were independent predictors for plaque rupture (all P < 0.05).

CONCLUSIONThe major predictors of vulnerable plaques were eccentric index (EI) and plaque area (PA), sVCAM-1 and AII-c% in this model.

Animals ; Atherosclerosis ; diagnosis ; diagnostic imaging ; C-Reactive Protein ; analysis ; Cholesterol, Dietary ; administration & dosage ; Diet, High-Fat ; Disease Models, Animal ; Early Diagnosis ; Male ; Plaque, Atherosclerotic ; diagnosis ; diagnostic imaging ; Rabbits ; Ultrasonography ; Vascular Cell Adhesion Molecule-1 ; blood

OBJECTIVETo establish nonalcoholic fatty liver disease (NAFLD) in young rats, and to investigate the metabolic characteristics of these rats.

METHODSFifteen male and fifteen female SD rats of 3 weeks old were randomly divided into three groups, normal group (N), 20% high fat group (HF1) and 30% high fat group (HF2). All the rats were fed under Specific pathogen Free (SPF) condition for 6 weeks and executed at the end of the 6th week. Body length and weight of each rat as well as their liver weight were measured for calculating Liver Index (LI). ALT, AST, TG, TC, INS, Glu and HOMA-IR in the blood were measured. Liver tissue homogenate was prepared for detecting TG level. The liver section was stained with HE and oil red. The expression of SPEBP-1 and leptin in liver was detected by immunostaining.

RESULTSThe typical pathological change of NAFLD was found in the rats of HF groups. In HF2 group, no rats died during the experiment and the degree of fat degeneration is homogeneous. Comparing with those in N group, TC (mmol/L), liver TG (mmol/L) and ALT levels in HF2 group were significantly elevated (2.50+/-0.39 vs 1.82+/-0.43, P less than 0.01; 25.38+/-13.29 vs 12.09+/-9.59, P less than 0.01 and 69.80+/-18.22 vs 48.00+/-10.45, P less than 0.01, respectively). Comparing with those in N group, TG level in HF1 group was significantly decreased (0.17+/-0.10 vs 0.32+/-0.12, P less than 0.05), Glu level in HF1 group was significantly elevated (12.33+/-3.48 vs 8.13+/-2.53, P less than 0.05). There were no significant difference between the results of AST, INS and HOMA-IR among the groups. The expression level of SREBP-1 and leptin increased in HF groups.

CONCLUSIONNAFLD can be induced by 30% high-fat feeding for 6 weeks in young rats, high-fat feeding induces the expression of SREBP-1 and leptin expression and fat synthesis.

Animals ; Blood Glucose ; metabolism ; Body Mass Index ; Cholesterol ; blood ; Dietary Fats ; administration & dosage ; Disease Models, Animal ; Fatty Liver ; blood ; etiology ; pathology ; Female ; Immunohistochemistry ; Insulin ; blood ; Insulin Resistance ; Leptin ; metabolism ; Liver ; metabolism ; pathology ; Male ; Non-alcoholic Fatty Liver Disease ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sterol Regulatory Element Binding Protein 1 ; metabolism ; Triglycerides ; blood

OBJECTIVETo observe the effects of (-)doxazosin(DOX), (+)DOX and (+/-)DOX on serum lipid levels and the mortality rates of the rabbits fed by an atherogenic diet.

METHODSMale white New Zealand rabbits were fed by an atherogenic diet for 4 weeks. 8 rabbits whose serum TC <10 mmol/L were confirmed as normal diet group and were fed normally. 40 rabbits whose serum TC >10 mmol/L were randomly divided into 4 groups (n=10): atherogenic diet group, atherogenic diet with (-)DOX group, atherogenic diet with (+)DOX group and atherogenic diet with (+/-)DOX group, which were intraperitoneally injected with (-)DOX, (+)DOX and (+/-)DOX for 9 weeks respectively. Normal and atherogenic diet group were intraperitoneally injected with double distilled water. After 9 weeks administration of (+/-)doxazosin and its enantiomers, effects of the three agents on serum levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were observed.

RESULTSThe mortality rate of the rabbits fed by an atherogenic diet for 13 weeks was 40%, and it was much higher than that of the rabbits fed by a normal diet (10%). The mortality rates in the rabbits treated with (-)DOX and (+/-)DOX were lower than that in the rabbits fed by a normal diet (10%). Serum LDL-C level of the rabbits was increased markedly after 4 weeks of atherogenic diet, and it was further increased significantly (P < 0.05 and P < 0.01) during the continued 9 weeks of atherogenic diet. However, serum LDL-C levels were not further increased significantly (P > 0.05) during the continued 9 weeks of atherogenic diet in the rabbits treated with (-)DOX, (+)DOX and (+/-)DOX, respectively.

CONCLUSION(-)DOX and (+/-)DOX increase the survival rate and improve LDL-C disorder mildly in the rabbits fed by an atherogenic diet. The improvements in LDL-C induced by (-)DOX and (+/-)DOX, however, might not be the reason for exploration about the increased survival rate in the rabbits fed by an atherogenic diet.

Animals ; Cholesterol, Dietary ; administration & dosage ; Diet, Atherogenic ; Doxazosin ; pharmacology ; Hyperlipidemias ; blood ; drug therapy ; etiology ; Lipids ; blood ; Male ; Rabbits ; Stereoisomerism

OBJECTIVETo investigate the effect of the sera of rabbits fed with Tongxinluo on the expression and secretion of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in U937 monocyte-derived macrophages.

METHODSAtherosclerosis was induced in rabbits by high-cholesterol feeding, and the serum was obtained from the rabbits after administration of the aqueous solution of Tongxinluo or simvastatin by gavage. U937 monocyte-derived macrophages were incubated with the sera at different concentrations for 24 hours, and the changes in MMP-9 and TIMP-1 gene expression and secretion were detected by RT-PCR and enzyme-linked immunosorbent assay, respectively.

RESULTSThe serum of rabbits fed with Tongxinluo concentration-dependently inhibited the expression and secretion of MMP-9 in U937 macrophages, but did not affect TIMP-1 expression or secretion.

CONCLUSIONTongxinluo may stabilize the atherosclerotic plaques by inhibiting the expression and secretion of MMP-9.

Animals ; Atherosclerosis ; blood ; etiology ; Cholesterol, Dietary ; administration & dosage ; Drugs, Chinese Herbal ; pharmacology ; Enzyme-Linked Immunosorbent Assay ; Humans ; Macrophages ; drug effects ; metabolism ; Male ; Matrix Metalloproteinase 9 ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Rabbits ; Reverse Transcriptase Polymerase Chain Reaction ; Serum ; Tissue Inhibitor of Metalloproteinase-1 ; biosynthesis ; genetics ; U937 Cells

Animals ; Aorta ; pathology ; Atherosclerosis ; blood ; etiology ; metabolism ; Chemokine CCL2 ; metabolism ; Cholesterol ; blood ; Cholesterol, Dietary ; administration & dosage ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Dehydroepiandrosterone ; pharmacology ; Diet, Atherogenic ; Immunohistochemistry ; Rabbits ; Random Allocation ; Triglycerides ; blood ; Vascular Cell Adhesion Molecule-1 ; metabolism

OBJECTIVE: To study the changes of reactive oxygen species(ROS), and the effect of Tongmai Tang on ROS. METHODS: Forty rabbits were randomly divided into 4 groups: a normal control group,a model group, a low dosage Tongmai Tang, and a high dosage Tongmai Tang administration group (n=10).The normal control group was fed with common food twice daily. The model group was fed with high cholesterol diet. The low dosage Tongmai Tang administration group was fed with high cholesterol diet as in the model group, together with Tongmai Tang at a lower dosage. The high dosage Tongmai Tang administration group was fed with high cholesterol diet as in the model group, together with Tongmai Tang at a higher dosage. After 16 weeks, the concentration of serum malondialdehyde (MDA),superoxide dismutase(SOD), and serum lipid were detected. RESULTS: In the model group, the concentration of serum SOD was significantly lower, while levels of serum MDA,CHO, and LDL were significantly higher than those in the control group(P<0.01). In the low dosage Tongmai Tang administration group, the concentration of serum CHO and LDL significantly decreased (P<0.05). In the high dosage Tongmai Tang administration group, the concentration of serum SOD significantly increased (P<0.05), whereas the level of serum MDA, CHO and LDL significantly decreased (P<0.01). MDA was positively correlated with serum CHO, LDL (r= 0.397 and 0.443, P<0.05), and SOD was negatively correlated with serum CHO, LDL(r= -0.407 and -0.429, P<0.01). CONCLUSION Tongmai Tang can decrease the concentration of serum CHO and LDL, and increase the level of SOD. Tongmai Tang may have antioxidation in atherosclerosis.
Animals ; Atherosclerosis ; blood ; Cholesterol, Dietary ; adverse effects ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Male ; Malondialdehyde ; blood ; Rabbits ; Superoxide Dismutase ; blood ; Triglycerides ; blood

OBJECTIVE: To explore the effect of niacin on the serum adiponectin concentration in hypercholesterolemia rabbit and the adiponectin concentration secreted by adipocytes in normal rabbits. METHODS: Ten male New Zealand white rabbits fed with high cholesterol diet for 8 weeks were randomly divided into 2 groups: (1) The high cholesterol group maintained a high cholesterol diet for 8 weeks. (2) The same cholesterol diet plus niacin (0.4g/kg*d ) were administrated for 6 weeks in the niacin group. A control group was fed with normal diet for 14 weeks. Subcutaneous adipose from the control group was collected for adipocyte culture. Matured adipocytes were incubated with various concentrations of niacin (0, 0.25, 0.5, 1.0, and 2.0micromol/L). Adiponectin concentrations in the serum and adipocyte culture supernatant were measured by enzyme-linked-immunosorbent assay. RESULTS: Compared with the control group, rabbits in the high cholesterol group showed higher serum levels of total cholesterol, and low density lipoprotein cholesterol (LDL-C), all of which were significantly reduced by niacin treatment (P<0.01),and serum high density lipoprotein-cholesterol (HDL-C) significantly increased (P<0.01). At 8th week, the mean adiponectin concentration of rabbits fed with high cholesterol diet was significantly lower than that of the control group[(1.268+/-0.039)mg/L vs.(1.449+/-0.107)mg/L,P<0.01]. Niacin treatment significantly elevated the serum adiponectin level which was positively related to HDL-C,and negatively related to TC and LDL-C. Cell experiment in vitro indicated that niacin could significantly induce the adiponectin secretion of adipocytes in a dose-dependent manner. CONCLUSION Niacin can significantly promote the adiponectin secretion of adipocytes, suggesting that niacin probably has an ability of elevating the serum adiponectin level in addition to lipid-lowering effect.
Adipocytes ; cytology ; drug effects ; metabolism ; Adiponectin ; blood ; metabolism ; Animals ; Cholesterol ; blood ; Cholesterol, Dietary ; administration & dosage ; toxicity ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Dose-Response Relationship, Drug ; Hypercholesterolemia ; blood ; etiology ; prevention & control ; Hypolipidemic Agents ; pharmacology ; Male ; Niacin ; pharmacology ; Rabbits ; Random Allocation