ox-LDL对血小板基质金属蛋白酶诱导剂释放的影响

目的 探讨氧化型低密度脂蛋白（ox-LDL）对血小板基质金属蛋白酶诱导剂（EMMPRIN,又名CD147）释放的影响。方法 分别以终浓度25 mg/L、50 mg/L和100 mg/L ox-LDL,对照组（磷酸盐,PBS）和100 mg/L天然LDL体外刺激洗涤血小板,以流式细胞仪检测血小板上CD147、α颗粒膜糖蛋白（CD62P）的表达,酶联免疫吸附法检测血小板上清液中可溶性CD147（sCD147）含量,共聚焦显微镜、透射电子显微镜观察血小板形态改变及颗粒释放。同时,阻断LOX-1受体后,再以流式细胞仪检测ox-LDL（50 mg/L和100 mg/L）刺激的血小板CD147表达。结果 25 mg/L、50 mg/L和100 mg/L ox-LDL处理组血小板CD147相对平均荧光强度（rMFI）（1.01±0.06、1.18±0.07、1.24±0.08）均高于对照组（0.86±0.10, P<0.01）和天然LDL组（0.89±0.11, P<0.01）。LOX-1阻断后,ox-LDL（50 mg/L和100 mg/L）处理组血小板CD147 rMFI（0.96±0.08、1.05±0.07）均下降（P<0.001）。ox-LDL处理后,血小板形态明显改变,并伴随颗粒释放。结论 ox-LDL通过与LOX-1结合诱导了血小板CD147的释放。     

脂蛋白相关磷脂酶A2与冠心病的相关性研究进展

脂蛋白相关磷脂酶A2（Lp-PLA2）是由炎性细胞产生并与低密度脂蛋白（LDL）结合,可水解氧化型低密度脂蛋白（ox-LDL）而产生炎症介质促进动脉粥样硬化。Lp-PLA2编码基因PLA2G7的单核苷酸多态性与冠心病之间存在明显相关性。Lp-PLA2作为新型的炎症标记物,与动脉粥样硬化的发生发展密切相关,作为冠心病的一个独立危险因素逐渐被关注,Lp-PLA2可能成为治疗冠心病的新靶点。本文就Lp-PLA2与冠心病的相关性研究新进展进行综述。     

Effects of simvastatin on carotenoid status in plasma

Background and aims

Carotenoids are potent antioxidants mainly transported in the low density lipoprotein (LDL) fraction. They may also influence the immune response and inverse associations with inflammatory markers have been reported. We investigated whether simvastatin, by exerting both lipid-lowering and anti-inflammatory effects, altered the carotenoid status in plasma.

Methods and results

A randomized, double-blind, placebo-controlled study design was applied. Eighty volunteers with mild to moderate hypercholesterolemia received either simvastatin 40 mg or placebo for 6 weeks. Lipids, oxidized LDL (ox-LDL), C-reactive protein (CRP), interleukin (IL)-6, oxygenated carotenoids (lutein, zeaxanthin, β-cryptoxanthin) and hydrocarbon carotenoids (α-carotene, β-carotene, lycopene) were measured in plasma. Simvastatin use was associated with significant reductions in total cholesterol, LDL, ox-LDL and CRP. Simvastatin therapy also resulted in reduced plasma levels of both oxygenated and hydrocarbon carotenoids. However, when adjusted for lipids, all carotenoids except β-cryptoxanthin showed significant increases after simvastatin therapy. Both crude and lipid-adjusted carotenoids were inversely correlated with CRP and IL-6 in plasma but the change in carotenoid status during simvastatin therapy was not specifically related to any changes in inflammatory markers.

Conclusions

To summarize, the change in carotenoid status during simvastatin therapy was mainly attributed to the lowering of cholesterol and not to the suppression of inflammatory activity. After adjustment for lipids, the levels of lutein, lycopene, α-carotene and β-carotene were significantly increased by simvastatin suggesting an increased ratio of carotenoids per particle.     

2型糖尿病患者高密度脂蛋白亚型分子组分的变化

目的 研究2型糖尿病患者高密度脂蛋白亚型分子构成成分含量、代谢关键酶活性变化及与血糖等指标的相关关系.方法 26例新发2型糖尿病患者与25例健康对照者留取血浆检测血糖、胰岛素和血脂谱.以改良一步沉淀法分离高密度脂蛋白3并检测其组分含量,并计算高密度脂蛋白2的主要组分含量.以荧光酶法测定胆固醇酯转运蛋白和磷脂转运蛋白活性.结果 (1)2型糖尿病组血高密度脂蛋白胆固醇与对照组无显著差异(P=0.579).(2)2型糖尿病组与对照组的胆固醇酯转运蛋白和磷脂转运蛋白活性均无明显差异.(3)2型糖尿病组高密度脂蛋白3以下组分含量较对照组明显减少(均P＜0.01):胆固醇为0.60±0.17 mmol/L比0.75±0.22mmol/L,磷脂为1.14±0.19 mmol/L比1.29±0.22 mmol/L,游离胆固醇为0.021±0.012 mmol/L比0.033±0.012mmoL/L,胆固醇酯为0.97±0.28 mmol/L比1.19±0.36 mmol/L.其中游离胆固醇和胆固醇酯含量与餐后血糖、糖化血红蛋白、胰岛素抵抗指数呈显著负相关(P＜0.05).(4)2型糖尿病组高密度脂蛋白2的载脂蛋白AI含量较对照组显著降低(604.8±233.3 mg/L比755.4±198.0 mg/L,P＜0.05),并与胰岛素抵抗指数、餐后血糖、血甘油三酯呈显著负相关(P＜0.05).结论 2型糖尿病患者高密度脂蛋白3和高密度脂蛋白2颗粒主要组分含量明显减少,并与血糖水平及胰岛素抵抗程度相关.     

丹参酮ⅡA对泡沫细胞胆固醇平衡的影响

目的通过体外细胞实验阐明丹参酮ⅡA对泡沫细胞胆固醇平衡的影响。方法体外培养小鼠RAW264.7细胞,以氧化型低密度脂蛋白诱导为泡沫细胞模型,并用不同浓度的丹参酮ⅡA进行处理,通过油红O染色观察细胞内脂质堆积情况,酶比色法定量检测细胞内总胆固醇和胆固醇酯的变化,荧光定量PCR和WesternBlot检测细胞中CD36、三磷酸腺苷结合盒转运体A1(ABCA1)、肝脏X受体α(LXRα)、过氧化体增殖物激活型受体α(PPARα)及PPARγ的mRNA和蛋白表达。结果 0～20 mg/L的丹参酮ⅡA对泡沫细胞增殖活力无明显影响,20 mg/L丹参酮ⅡA干预后,泡沫细胞内胆固醇酯与总胆固醇的比值显著降低,细胞内脂质累积减少,并上调AB-CA1、LXRα和PPARα的mRNA和蛋白表达,但对CD36表达无明显作用。结论丹参酮ⅡA能抑制泡沫细胞的形成,其机制可能是通过诱导PPARα、LXRα和ABCA1表达,促进胆固醇的外排。     

内皮脂肪酶与高密度脂蛋白及动脉粥样硬化的关系

高密度脂蛋白具有一定的抗动脉粥样硬化的作用,而内皮脂肪酶可水解高密度脂蛋白,进而影响动脉粥样硬化的进展,故深入探讨三者关系,可能为动脉粥样硬化相关疾病的防治提供崭新的靶点.     

Impaired fasting glucose: Pro-diabetic, “atheroprotective” and modified by metabolic syndrome

AIM: To investigate whether impaired fasting glucose (IFG) confers cardiovascular risk.METHODS: A non-diabetic population-based sample representative of middle-aged and elderly Turks was studied at 8.5 years’ follow-up for incident diabetes and coronary heart disease (CHD). Metabolic syndrome (MetS) was defined by ATP-III criteria modified for male abdominal obesity, and IFG and type 2 diabetes were identified by criteria of the American Diabetes Association. Stratification by presence of MetS was used. Outcomes were predicted providing estimates for hazard ratio (HR) obtained by use of Cox proportional hazards regression analysis in models that controlled for potential confounders.RESULTS: In 3181 adults (aged 52 ± 11.5 years at baseline), analysis stratified by MetS, gender and IFG status distinguished normoglycemic subjects by a “hypertriglyceridemic waist” phenotype consisting of significantly higher waist circumference, fasting triglyceride and lower high-density lipoprotein-cholesterol, regardless of gender and MetS. Additionally, lipoprotein (Lp) (a) tended to be lower in (especially female) participants with MetS. Multivariable linear regression in a subset of the sample demonstrated decreased Lp (a) levels to be associated with increased fasting glucose and insulin concentrations, again particularly in women. In Cox regression analysis, compared with normoglycemia, baseline IFG adjusted for major confounders significantly predicted incident diabetes at a 3-fold HR in men and only women with MetS. Cox models for developing CHD in 339 individuals, adjusted for conventional risk factors, revealed that IFG status protected against CHD risk [HR = 0.37 (95%CI: 0.14-0.998)] in subjects free of MetS, a protection that attenuated partly in male and fully in female participants with MetS.CONCLUSION: IFG status in non-diabetic people without MetS displays reduced future CHD risk, yet is modulated by MetS, likely due to autoimmune activation linked to serum Lp (a).     

MRI compatible MS2 nanoparticles designed to cross the blood–brain-barrier: providing a path towards tinnitus treatment

Fundamental challenges of targeting specific brain regions for treatment using pharmacotherapeutic nanoparticle (NP) carriers include circumventing the blood–brain-barrier (BBB) and tracking delivery. Angiopep-2 (AP2) has been shown to facilitate the transport of large macromolecules and synthetic nanoparticles across the BBB. Thus, conjugation of AP2 to an MS2 bacteriophage based NP should also permit transport across the BBB. We have fabricated and tested a novel MS2 capsid-based NP conjugated to the ligand AP2. The reaction efficiency was determined to be over 70%, with up to two angiopep-2 conjugated per MS2 capsid protein. When linked with a porphyrin ring, manganese (Mn²⁺) remained stable within MS2 and was MRI detectable. Nanoparticles were introduced intracerebroventricularly or systemically. Systemic delivery yielded dose dependent, non-toxic accumulation of NPs in the midbrain. Design of a multifunctional MRI compatible NP platform provides a significant step forward for the diagnosis and treatment of intractable brain conditions, such as tinnitus.