补肾法对实验性绝经后动脉粥样硬化作用机理的实验研究

为探讨补肾法对实验性绝经后动脉粥样硬化作用机理 ,将家兔以摘除卵巢和高脂伺料喂养的方法造模 ,在此基础上给于补肾中药 (淫阳藿、菟丝子、泽泻、熟地黄等 ) ,并与肌注雌二醇组对照 ,12周后观察动物血脂、血一氧化氮(NO)、内皮素 (ET)、超氧化物歧化酶 (SOD)和丙二醛 (MDA)的含量。结果 :造模兔与正常兔相比 ,血脂、ET、MDA含量升高 ,而NO含量、SOD活性降低 ;中、西药物治疗组动物的上述指标均有恢复正常的趋势 (P <0 0 5～ 0 0 1) ,但两治疗组之间无明显差异。提示补肾中药可替代雌二醇 。

儿茶素对鹌鹑实验性动脉粥样硬化的影响

用高脂饲料诱发鹌鹑动脉粥样硬化 ,观察了儿茶素对动脉粥样硬化模型的影响。将 30只雄性 30天龄鹌鹑随机分成 3组 ,每组 10只。对照组 (N)给予普通饲料 ;高脂组 (L)给予高脂饲料 ;儿茶素防治组 (L +C)给予高脂饲料的同时喂以儿茶素水制剂。以上各组均喂养 3个月后全部处死 ,取血清、肝脏检测相关指标 ,并做冰冻切片及电镜切片进行评价。结果显示儿茶素防治组与高脂组相比 ,鹌鹑血清TC、TG、LDL C、MDA和Fru水平显著下降 (P <0 0 1) ,血清SOD活性、HDL C、NO2- NO3- 含量和肝脏SOD、ALT、AST活性及NO2- NO3- 含量都显著升高 (P <0 0 1)。说明儿茶素具有明显的调节血脂、抗脂质过氧化、减轻脂肪肝。

3种化痰方剂含药血清超滤组分对THP-1源性巨噬细胞活性及泡沫化的影响

【目的】观察3种化痰方剂(黄连温胆汤、瓜蒌薤白半夏汤、二陈汤)含药血清超滤组分对人白血病单核细胞(THP-1)源性巨噬细胞活性及其泡沫化的影响。【方法】以佛波酯(PMA)诱导THP-1为巨噬细胞,经氧化低密度脂蛋白(ox-LDL)处理建立动脉粥样硬化泡沫细胞模型;制备3种化痰方剂含药血清及空白血清经10 KD超滤器超滤后,作用于泡沫细胞模型。采用四甲基偶氮唑盐(MTT)法及油红染色观察各组对巨噬细胞存活率和泡沫化的影响;通过流式细胞术检测各组对巨噬细胞凋亡率的影响。【结果】THP-1经100 nmol/L PMA诱导24 h后,与50μg/m L ox-LDL共孵育24 h,获得泡沫细胞模型。黄连温胆汤含药血清超滤成分作用于巨噬细胞,可明显提高存活率,抑制泡沫化,降低细胞凋亡率。二陈汤和瓜蒌薤白半夏汤含药血清超滤成分可增加泡沫化,未见显著抗凋亡作用。【结论】黄连温胆汤具有抗动脉粥样硬化作用,可能与其能抗巨噬细胞凋亡,降低巨噬细胞脂质吞噬作用相关;二陈汤和瓜蒌薤白半夏汤可能具有提高巨噬细胞脂质吞噬功能的作用。

神经节苷脂GM_3对小鼠巨噬细胞脂质含量的影响

目的:探讨神经节苷脂GM3对小鼠巨噬细胞(Mφ)脂质含量的影响。方法:采用45 g/L无菌可溶性淀粉溶液刺激后,收集昆明种小鼠腹腔Mφ,经体外培养分为6组,应用常规酶法观察各组Mφ总胆固醇、游离胆固醇、胆固醇酯和甘油三酯的变化。结果:GM3与低密度脂蛋白(LDL)同时存在,可促进Mφ对LDL的吸收,提高Mφ的脂质含量,而LDL、GM3单独存在时,不能显著升高Mφ内各种脂质含量。结论:GM3可能通过激活Mφ产生多种生物活性因子氧化LDL或通过GM3对LDL的非氧化修饰,促进Mφ对LDL的吸收,引起脂质堆积。

Primary Mechanisms for Novel Compound Pivanampeta Against Atherosclerosis in Rat and Rabbit Model of Atherosclerosis

Aim To investigate the anti-atherosclerotic mechanisms of the novel compoundpivanampeta in the early and later stages of atherosclerosis evolution. Methods Rats or rabbits wererandomly assigned to the control, the model and the pivanampeta-treated groups. The rats or rabbitsin the model group and the pivanampeta-treated group were fed with hypercholesterol diet. Thecarotids of rabbits were cut into pieces and stained with HE. The rat or rabbit serum levels of TC,LDL-CHO, HDL-CHO, IL-8, ET-1, PGI_2, TXA_2, and NO were assayed. The expressions of MCP-1 and IL-8mRNA on rabbit carotid were determined by semi-quantitative RT-PCR. Results Pivanampeta exerted aninhibitory effect on TXA_2 formation without PGI_2 production in the early and later stages ofatherosclerosis. The significantly increased release of NO and the decreased release of IL-8 in theanimals in pivanampeta-treated group were both detected in the rat atherosclerosis model. In therabbit atherosclerosis model the expressions of IL-8 and MCP-1 mRNA in pivanampeta-treated groupwere decreased significantly. However, the treatment with pivanampeta had no effect on the levels ofplasma cholesterol, MDA and SOD. Conclusion The increase of serum NO contents and the decrease ofplasma TXA_2 level, as well as its inhibition of expression of IL-8 and MCP-1 are probably involvedin the mechanisms underlying the anti-atherosclerotic effects of pivanampeta.

减压应激对血小板分型与聚集功能的影响

1 方法应用Wistar大鼠60只和家兔40只,随机分为实验组和对照组,每组动物各半复制动物粥样硬化(AS)模型.试验组以15～20m/s速度减压,当大鼠上升至7000m(家兔6000m)时,停留20min后与对照组(不减压)同时取心血进行血小板分型和聚集功能检测.

A randomized, open-label, multicentre study to evaluate plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus and arteriosclerosis obliterans when treated with Probucol and Cilostazol

Objectives To evaluate the plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus （T2DM） and arteriosclerosis obliteran （ASO） when treated with Probucol plus Cilostazol in combination and individually. Methods In this open-label study, patients aged 40-75 years were randomized to receive conventional therapy alone, or with Cilostazol 100 mg bid, or with Probucol 250 mg bid, or with both in combination. Endpoints included changes in plasma biomarker and safety at 12 weeks. Results Of the 200 randomized pati- ents, 165 for per-protocol and 160 for the safety （QTc intervals） were set, respectively. Probucol significantly reduced total cholesterol （P 〈 0.001）, low-density lipoprotein cholesterol （LDL-C）, （P = 0.01）, and high-density lipoprotein cholesterol （HDL-C） （P 〈 0.001） compared with conventional therapy. Cilostazol was effective in increasing HDL-C （P = 0.002） and reducing triglycerides levels （P 〈 0.01） compared with conventional therapy. A trend towards significance was observed for the difference between conventional therapy alone and Probucol plus Cilostazol group for the change in oxidized low-density lipoprotein （Ox-LDL, P = 0.065）. No significant effects on the majority of the remaining biomarkers were found across the treatment groups. Conclusions We have confirmed that Ox-LDL could be a possible plasma atherosclerotic biomarker among the evaluated biomarkers, which reflected the synergetic effect of Cilostazol plus Probucol in patients with T2DM and ASO shown previously in preclinical studies.

Atherosclerosis： from biology to pharmacological treatment

A recent explosion in the amount of cardiovascular risk has swept across the globe. Primary prevention is the preferred method to lower cardiovascular risk. Lowering the prevalence of obesity is the most urgent matter, and is pleiotropic since it affects blood pressure, lipid profiles, glucose metabolism, inflammation, and atherothrombotic disease progression. Given the current obstacles, success of primary prevention remains uncertain. At the same time, the consequences of delay and inaction will inevitably be disastrous, and the sense of urgency mounts. Pathological and epidemiological data confirm that atherosclerosis begins in early childhood, and advances seamlessly and inexorably throughout life. Risk factors in childhood are similar to those in adults, and track between stages of life. When indicated, aggressive treatment should begin at the earliest indication, and be continued for many years. For those patients at intermediate risk according to global risk scores, C-reactive protein, coronary artery calcium, and carotid intima-media thickness are available for further stratification. Using statins for primary prevention is recommended by guidelines, is prevalent, but remains under prescribed. Statin drugs are unrivaled, evidence-based, major weapons to lower cardiovascular risk. Even when low density lipoprotein cholesterol targets are attained, over half of patients continue to have disease progression and clinical events. Though clinical evidence is incomplete, altering or raising the blood high density lipoprotein cholesterol level continues to be pursued. The aim of this review is to point out the attention of key aspects of vulnerable plaques regarding their pathogenesis and treatment.

Subclinical hypothyroidism is associated with lipid-rich plaques in patients with coronary artery disease as assessed by optical coherence tomography

Background Subclinical hypothyroidism （SCH） has recently been acknowledged as an unconventional risk factor for coronary artery disease （CAD） and characterized by poor prognosis, which may be due to atherosclerotic plaque characteristics. We conducted this study to observe coronary plaque characteristics in coronary artery disease patients with concomitant SCH. Methods Patients with coronary artery disease were enrolled in the study and divided into an SCH group （patients, n = 26; plaques, n = 35） and a non-SCH group （patients, n = 52; plaques, n = 66）. They were divided 1：2 according to propensity-matched analysis including age, diabetes mellitus, gender, CAD severity and culprit vessel. Optical coherence tomography （OCT） imaging was performed on all patients, and images were analyzed by two inde- pendent investigators. Lipid-rich plaques （LRP）, the precursor of vulnerable plaques, were defined as having more than one quadrant occu- pied with lipid pool. Maximum lipid arcs were simultaneously recorded. Fibrotic plaques and calcific plaques were also identified. The pres- ence of coronary dissection, plaque erosion, thrombus, macrophage, calcific nodule, thin-cap fibroatheroma and micro channel were all noted. Results The ratio of LRP in SCH group was significantly higher than that in non-SCH group （54% vs. 30.3%, P = 0.037）. That was the case as well for the maximum lipid arcs value （181.5°± 61.6° vs. 142.1° 4± 35.9°, p = 0.046）. While thin-cap fibroatheroma （TCFA） was detected, no difference was identified between the two groups in either TCFA ratio （20% vs. 16.7%, P = 0.579） or fibrous cap thickness （57.5 4± 14.0 vs. 63.5 4±10.7 gin, P = 0.319）. Other OCT characteristics such as dissection, plaque erosion, thrombus, macrophage shadow and calcific nodule were also similar. ConcLusion Higher ratio of LRP with greater lipid arc in SCH patients may be related to the plaque instability and poor prognosis in CAD patients with SCH.

The comparative efficacy of ezetimibe added to atorvastatin 10 mg versus uptitration to atorvastatin 40 mg in subgroups of patients aged 65 to 74 years or greater than or equal to 75 years

Background Coronary heart disease （CHD） risk increases with age; yet lipid-lowering therapies are significantly under-utilized in patients 〉 65 years. The objective was to evaluate the safety and efficacy of lipid-lowering therapies in older patients treated with atorvastatin 10 nag ＋ ezetimibe 10 mg （EZ/Atorva） vs. increasing the atorvastatin dose to 40 mg, Methods Patients 〉 65 years with atherosclerotic vascular disease （LDL-C ≥1.81 mmol/L） or at high risk for coronary heart disease （LDL-C 〉 2.59 mmol/L） were randomized to EZ/Atorva for 12 wk vs. uptitration to atorvastatin 20 nag for 6 wk followed by atorvastatin 40 nag for 6 wk. The percent change in LDL-C and other lipid parameters and percent patients achieving prespecified LDL-C levels were assessed after 12 wk. Results EZ/Atorva produced greater reductions in most lipid parameters vs. uptitration of atorvastatin in patients 〉 75 years （n = 228）, generally consistent with patients 65-74 years （n = 812）. More patients achieved LDL-C targets with combination therapy vs. monotherapy in both age groups at 6 wk and in patients 〉 75 years at 12 wk. At 12 wk, more patients 〉 75 years achieved LDL-C targets with monotherapy vs. combination therapy. EZ/Atorva produced more favorable improvements in most lipids vs. doubling or quadrupling the atorvastatin dose in patients 〉 75 years, generally consistent with the findings in patients 65-74 years. Conclusions Our results extended previous findings demonstrating that ezetimibe added to a statin provided a generally well-tolerated therapeutic option for improving the lipid profile in patients 65 to 74 years and 〉 75 years of age.

Angina rapidly improved with a plant-based diet and returned after resuming a Western diet

Atherosclerosis and its related cardiovascular disease is the most common cause of morbidity and mortality in the Western world. The roots of this disease may lie, in part, in dietary and lifestyle behaviors, indicating that modifica- tion of these behaviors may lead to profound improvements.

Treatment of dyslipidemia in the elderly

Dyshpidemia is a well-established risk factor for atherosclerosis. Treating dyslipidemia in elderly patients requires specific knowledge and understanding of common dyslipidemias and the relative safety of various pharmacologic agents in the presence of possible multiple comorbidities. Lifestyle modification remains the first step in the treatment of dyslipidemia; however, it can be difficult to sustain and achieve acceptable compliance in the elderly and it is best used in combination with drug therapy. Statins are widely accepted as the first-line therapy. Several recent studies have demonstrated that statins are safe and effective in the elderly. However, it is important to note that there is very limited data regarding the effects of dyslipidemia treatment on morbidity and mortality in patients over 85 years of age. In summary, the clinicians must recognize that the presence of dyslipidemia in the elderly poses substantial risk of coronary events and stroke. The available evidence has demonstrated that in most elderly patients who are at increased risk for cardiovascular morbidity and mortality, treatment of dyslipidemia with appropriate therapy reduces the risk, and when used carefully with close monitoring for safety, the treatment is generally well tolerated. With increasing life expectancy, it is critical for physicians to recognize the importance of detection and treatment of dyslipidemia in the elderly.

Energy and Nutritional Properties of the White Mulberry （Morus alba L.）

The white mulberry （Morus alba L.） had been forgotten in Europe or known only as a plant associated with breeding of mulberry silkworms （Bombyx mori L.）. The initial studies have shown great potential of this plant in energy, food and pharmaceutical industries. The leaves and fruits contain very valuable bioactive substances, which may be used in health care. Antioxidants of plant origin include flavonoids and vitamin C （ascorbic acid）, and these substances are present in high amounts in anatomical parts of white mulberry. It has also been reported on the medicinal properties of this plant and its use in preventing diseases, such as atherosclerosis, diabetes, obesity and cancer. The food industry increasingly uses the white mulberry in food to provide human organism with precious bioactive substances. Functional food, due to the presence in its composition of valuable components, is beneficial to human health. What is more, very fast growth of mulberry causes that biomass of the plant may be used as biofuel or energy plant. The aim of this paper is to present the possibility of using the white mulberry as a raw material for functional foods and as an energy plant.

Effects of valsartan on oxidative stress and the atherogenesis

Objective: To investigate the therapy effect of valsartan on oxidative stress and the formation of atherosclerosis of rabbit. Methods: An atherosclerotic rabbit model was established by feeding high cholesterol diet supplemented by bovine serum albumin injection bolus. The rabbits were randomly divided into the control, model, and valsartan treated group, six rabbits in each group. Blood samples were collected at the end of 8 weeks for examination of serum lipid levels and MDA levels; the aortas were harvested for histological morphometry analysis, vascular cell adhesion molecule-1 (VCAM-1) immunohistochemical analysis and in situ superoxide detection to reflect the activity of NAD(P)H oxidase. Results: Rabbits fed with high cholesterol diet showed higher serum lipids levels than those fed with normal diet(P<0.01). Treatment with valsartan (10 mg/kg per day) did not alter serum lipids levels. But the serum MDA level and ratio of lesion to intima area reduced significantly compared with model group(P<0.05). The expression of VCAM-1 decreased significantly in the valsartan treated group than in the model group (P<0.05).In addition, in situ superoxide detection also show the markedly reduction of superoxide as a result of valsartan treatment. Conclusion: These results indicate that the valsartan treatment can reduce the atherosclerotic progression, the mechanisms of which may include the inhibiting the NAD(P)H oxidase activity to produce superoxide and the downregulating the expression of redox sensitive genes in the downstream, such as VCAM-1.

Computational Fluid Dynamics Simulation on Biomedical Stent Design

The stent was a major breakthrough in the treatment of atherosclerotic vascular disease. The permanent vascular implant of a stent, however, changes the intra-stent blood flow hemodynamics. There is a growing consensus that the stent implant may change the artery wall shear stress distribution and hence lead to the restenosis process. Computational fluid dynamics （CFD） has been widely used to analyze hemodynamics in stented arteries. In this paper, two CFD models （the axisymmetric model and the 3-D stent model） were developed to investigate the effects of strut geometry and blood rheology on the intra-stent hemodynamics. The velocity profile, flow recirculation, and wall shear stress distribution of various stent strut geometries were studied. Results show strong correlations between the intra-stent hemodynamics and strut geometry. The intra-stent blood flow is very sensitive to the strut height and fillet size. A round strut with a large fillet size shows 36% and 34% reductions in key parameters evaluating the restenosis risk for the axisymmetric model and the 3-D stent model, respectively. This suggests that electrochemical polishing, a surface-improving process during stent manufacturing, strongly influences the hemodynamic behavior in stented arteries and should be controlled precisely in order to achieve the best clinical outcome. Rheological effects on the wall shear stress are minor in both axisymmetric and 3-D stent models for the vessel diameter of 4 mm, with Newtonian flow simulation tending to give more conservative estimates ofrestenosis risk. Therefore, it is reasonable to simulate the blood flow as a Newtonian flow in stented arteries using the simpler axisymmetric model. These findings will provide great insights for stent design optimization for potential restenosis improvement.

Plasma metabolic biomarkers for syndrome of phlegm and blood stasis in hyperlipidemia and atherosclerosis

OBJECTIVE： To explore the plasma metabolite pro- files in patients with the syndrome of phlegm and blood stasis in hyperlipidemia and atherosclerosis （As）, and to search for the metabolic biomarkers of the syndrome. METHODS： The plasma metabolite profiles of 31 patients with the syndrome of phlegm and blood stasis in hyperlipidemia and As, 6 patients with syn- dromes without phlegm and blood stasis, and 10 healthy subjects were analyzed by gas chromatog- raphy-mass spectrometry （GC-MS）. Partial least squares-discriminant analyses （PLS-DA） were used to carry out the pattern-recognition analyses of the data. The plasma metabolic biomarkers of patients were obtained by variable importance plot value （VlP value） and Student＇s t-test. The structures ofbiomarkers were defined by the National Institute of Standards and Technology （NIST） database. RESULTS： PLS-DA score plots of plasma metabo- Iomes did not show overlap between the phlegm-blood stasis syndrome group and syn- dromes without phlegm and blood stasis group, whereas significant differences in the concentra- tions in the plasma of 5 metabolites were found （P〈 0.05）. They were identified as urine, isoleucine, gluc- uronic acid, palmitic acid and glycerol by searching in NIST database. The concentrations of four metab- olites in the plasma of patients with syndrome of phlegm and blood stasis were higher than those with syndromes without phlegm and blood stasis, whereas the glycerol concentration was lower. CONCLUSION： Compared with patients with syn- dromes without phlegm and blood stasis, five me- tabolites showed abnormal levels in patients with the syndrome of phlegm and blood stasis. These metabolites could be diagnostic and prognostic biomarkers.

Role of C5a-C5aR axis in the development of atherosclerosis

Complement component 5a(C5a)is a 74 amino acid glycoprotein and an important proinflammatory mediator that is cleaved enzymatically from its precursor,C5,on activation of the complement cascade.C5a is quickly metabolised by carboxypeptidases,forming the less-potent C5a desArg.C5a and C5a desArg interact with their receptors(C5aR and C5L2),which results in a number of effects which are essential to the immune response.C5a has a broad range of biological effects throughout the human body because the widespread expression of C5a receptors throughout the human organs enables C5a and C5a desArg to elicit a broad range of biological effects.Recently,accumulating evidence in humans and experimental animal models shows that the C5a-C5aR axis is involved in the development of atherosclerosis lesions.The absence or blockade of C5aRs greatly reduces the formation of atherosclerotic lesions or wire-injury-induced neointima formation in atherosclerosis-prone mice.Serum C5a level was related to the major adverse cardiovascular events in patients with advanced atherosclerosis and those with drug-eluting stent implantation.Thus,the C5a-C5aR axis may be a significant pathogenic driver of arteriosclerotic vascular disease,making C5a-C5aR inhibition an attractive therapeutic strategy.

Enhanced External Counterpulsation Treatment Inhibitting Advanced Atherosclerotic Plaque Progression by Augmenting the Plaque Wall Stress： An in vivo FSI Study Based on Animal Experiment

Enhance extemal counterpulsation （ECP） procedure has exhbited itself to be an effective therapy for the m anagem entof ischem ic card iovascu lar diseases, However, considering that EECP significantly increases the acute diastolic pressure, whether it will intervene in the chronic progression of advanced plaque causing great concern in clilical applkation, but yet rein ains elusive presently. In the current paper, a flu id-structure interface （FSI） num erical model of artery with p iaque corn ponent w as developed based on in vivo hem odynam ic m easurem entperfotm ed h a porcine model, to caku late the m echanical stresses of the plaque before and during EECP, and h lum to assess the potential effects of long-term EECP treatm ent on plaque progression. The resu Its show that E E C P augm ented the wall shear stress （WSS） and plaque w all stress （PWS） over the card lac cycles, aswell as the spacial oscillatory of W SS （WSSG ）. Durhg EECP treatm ent, the PW S level respectively raised 6.82% and 6.07% in two simulation cases. The currentpilot study suggests that E E C P treatm entre ay p lay a positive effect on inh biting the conthued plaque progression by hcreashg the PW S level over the card iac cycles. Meanwhile, the plaque morphology should be taken into consideration while m aking patient- specific plan for Ion g- term E E C P treatment in clinic.