Pacientes Naïve Infectados por HIV Apresentam Disfunção Concomitante com Diminuição de Anticorpos Naturais contra Autoantígenos Derivados da Apolipoproteína B Definidos

Fundamento:Fatores de risco definidos para HIV e tradicionais podem estar associados a um aumento de eventos cardiovasculares. Estudos recentes sugerem que a resposta imune humoral à LDL modificada pode estar associada ao processo de aterosclerose.Objetivos:Avaliar a presença de anti-LDL oxidada e de peptídeos derivados da Apolipoproteína B no sangue, bem como sua associação à função endotelial na infecção por HIV.Métodos:Este estudo incluiu consecutivamente sujeitos com idade, sexo e dados demográficos correspondentes em dois grupos: (1) indivíduos infectados com HIV e naïve para terapia antiviral e (2) indivíduos não infectados. A aterosclerose subclínica foi avaliada pela espessura íntima-média, utilizando-se a ultrassonografia das artérias carótidas. A função endotelial foi determinada pela dilatação mediada por fluxo (DMF) da artéria braquial por ultrassonografia. Os níveis de autoanticorpos (IgM, IgG) de lipoproteínas de baixa densidade antioxidadas (LDL-ox), fragmentos de peptídeos antiapolipoproteína B (peptídeos ApoB-D e 0033G-Cys), e citocina foram avaliados por meio de ELISA.Resultados:Os resultados deste estudo não mostraram diferenças na aterosclerose subclínica entre os grupos. Entretanto, os sujeitos infectados com HIV apresentaram uma DMF mais baixa, em comparação com os sujeitos não infectados. Portanto, os sujeitos infectados com HIV apresentaram níveis mais altos de citocinas inflamatórias, títulos de IgG anti-LDL-ox, e IgG anti-ApoB-D. Em contraste, títulos de IgM anti-ApoB-D foram mais baixos em indivíduos infectados com HIV e associados a funções endoteliais diminuídas.Conclusões:Os resultados deste estudo mostram que a infecção por HIV, em sujeitos naïve, está associada à disfunção endotelial e à diminuição de anticorpos naturais para antígenos Apo-B.     

阿托伐他汀对ApoE基因敲除小鼠动脉粥样硬化病变中TRPC5表达的影响

目的:观察载脂蛋白E基因敲除(Apo E-/-)小鼠动脉粥样硬化斑块形成过程中血管平滑肌细胞瞬时受体电位通道5(TRPC5)蛋白的表达变化,以及阿托伐他汀药物干预对TRPC5的影响并探讨其作用机制。方法:将40只6周龄雄性Apo E-/-小鼠随机分为模型组和他汀干预组,高脂饲料喂养建立动脉粥样硬化模型。他汀干预组给予阿托伐他汀(20 mg·kg-1·d-1)灌胃,模型组给予等量生理盐水灌胃。20只同龄雄性野生型C57BL/6J小鼠给予普通饲料喂养作为正常对照组。各组小鼠分别喂养至20和30周龄,分别取10只取血并处死。取主动脉根部做石蜡切片行HE染色形态学观察,测量并计算斑块相对面积;免疫组织化学染色检测各组小鼠TRPC5蛋白表达变化。取胸腹段主动脉行实时荧光定量PCR,检测主动脉中TRPC5通道蛋白mRNA的表达水平。结果:与模型组相比,阿托伐他汀干预组的血脂明显下降,斑块总面积明显减小,TRPC5蛋白水平及mRNA含量明显下降;30周龄模型组的TRPC5蛋白表达稍高于20周龄模型组,但差异无统计学意义;30周干预组较20周干预组相比,TRPC5水平有降低趋势且差异有统计学意义。结论:阿托伐他汀可能通过下调TRPC5蛋白表达从而延缓动脉粥样硬化进程。     

β2-糖蛋白Ⅰ与氧化脂蛋白复合物的研究进展

β2-糖蛋白-Ⅰ(beta2-glycoprotein Ⅰ,β2-GPI)在体内与氧化低密度脂蛋白、氧化脂蛋白(a)结合形成复合物,在伴有高动脉粥样硬化风险的自身免疫性疾病及心脑血管疾病等患者血清中水平显著升高,且与体内高氧化应激状态和炎症反应相关,是预测动脉粥样硬化发生、发展的新的危险因素.本文就近年来有关β2-GPI与氧化脂蛋白复合物的检测和临床意义研究作一综述.     

CD36与动脉粥样硬化的相关性研究

目的 探讨清道夫受体CD36在动脉粥样硬化患者血清中的变化及CD36在人主动脉粥样硬化组织中的表达情况,并研究两者的相关性及其临床意义.方法 选择心血管内科冠心病患者(CHD) 100例作为冠心病组,其中包括稳定型心绞痛(SAP)31例,不稳定型心绞痛(UAP) 29例,急性心肌梗死(AMI)40例.同时选择健康体检者50例作为对照组.ELISA法对两组血清进行CD36的浓度检测,检测其甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、hs-CRP、同型半胱氨酸(Hcy)含量,并对结果数据进行统计学分析.选择经冠脉造影诊断为冠心病的心脏手术患者的冠状动脉组织,同时选择因意外伤害需要心脏手术患者的冠状动脉组织作为对照组,免疫组化法检测两组组织中的CD36的表达.结果 ELISE法检测健康对照组CD36的含量为3.81 ±0.95pg/mL,而冠心病患者血清中CD36含量为25.17±3.76pg/mL,冠心病患者血清中CD36含量较健康对照组明显升高,差异有统计学意义(P＜0.05).其中稳定型心绞痛(SAP)CD36含量为18.68 ±2.17 pg/mL,不稳定型心绞痛(UAP)24.19±0.82 pg/mL,急性心肌梗死(AMI)27.17±5.83 pg/mL,不稳定型心绞痛和急性心肌梗死组CD36水平较稳定型心绞痛的明显升高(P＜0.01).动脉粥样硬化患者组CD36表达明显高于健康对照组,差异有统计学意义(x2 =23.018,P＜0.05).结论 清道夫受体CD36在动脉粥样硬化患者血清中浓度明显升高,且在动脉粥样硬化患者组织中高表达,临床上动脉粥样硬化患者检测CD36具有重要临床意义.     

Reducing risk of stroke in patients with acute coronary syndrome: is screening for asymptomatic carotid disease useful?

Stroke is a rare but severe event after acute coronary syndrome. Relations between both arterial territories are still discussed but prevalence of asymptomatic carotid stenosis potentially implicated in the mechanism of stroke is under-investigated. This study aimed to determine the prevalence of asymptomatic carotid stenosis in that population and review the value of screening in a view to potential surgical correction or other preventive therapies. Systematic carotid Doppler ultrasound screening was implemented on 152 consecutive patients admitted to the intensive care unit due to acute coronary syndrome. Fifty-two percent of patients had at least one carotid artery stenosis determined using the NASCET method. Forty-three percent had at least one carotid stenosis <30%, 6% had mild (30–60%) stenosis, and 2.6% had high-grade (>60%) stenosis. Existence of carotid stenosis was associated with age, diabetes mellitus, hypertension, and with the extent of the coronary atherosclerosis (left main artery stenosis). In multivariate analysis, age and diabetes were independently associated with existence of a carotid stenosis. When ultrasound screening was restricted to patients identified by multivariate analysis, the prevalence of carotid stenosis potentially requiring surgical treatment rose to 4.6%. The frequency of asymptomatic carotid atherosclerosis was high in this population but lesions were mild. While the small number of high-grade lesions indicates that systematic screening is not to be recommended, screening of patients aged >65 years or with diabetes, or both, with a view to surgery may be envisaged, since the role of mild stenosis in the occurrence of stroke remains debatable.     

Oxidized to non-oxidized lipoprotein ratios are associated with arteriosclerosis and the metabolic syndrome in diabetic patients

Background and aimType 2 diabetic patients have a greater prevalence of the metabolic syndrome, oxidative stress and accelerated atherosclerosis, compared to non-diabetics. We examined the association between biomarkers of lipid peroxidation and the presence of atherosclerosis and the metabolic syndrome in diabetic patients.Methods and resultsWe studied oxidized LDL (OxLDL), OxLDL/LDL, OxLDL/HDL, lipoperoxides, autoantibodies against OxLDL (OxLDL-Ab), diene formation of LDL (lag phase), vitamin E, vitamin E/cholesterol and PON1 polymorphisms (−108C > T, 55T > A, and 192A > G) in 166 non-smoking type 2 diabetic patients, 119 fulfilling the criteria for the metabolic syndrome, 73 with atherosclerosis and 93 without atherosclerosis. Patients with macrovascular disease had higher values of OxLDL/LDL (11%; P = 0.016), OxLDL/HDL (18%; P = 0.024) and OxLDL-Ab (12%; P = 0.046). OxLDL/LDL and OxLDL/HDL were correlated with the number of components of the metabolic syndrome (P < 0.001). PON1 polymorphisms were not associated to LDL oxidation markers, only PON1 (−108TT) was weakly associated with higher OxLDL-Ab concentrations (22%; P = 0.040) in patients with atherosclerosis.ConclusionOxLDL/LDL, OxLDL/HDL and OxLDL-Ab are the most useful clinical parameters of lipoprotein oxidation for discriminating the presence of macrovascular disease in diabetic patients. The presence of the metabolic syndrome in these patients is also associated with an increase in the oxidized lipoprotein ratios.     

Aortic Intima-Media Thickness and Mean Platelet Volume in Children With Type 1 Diabetes Mellitus

Background:

Diabetes mellitus type 1 is the most common endocrine metabolic disorder occurring in childhood and adolescence due to the autoimmune destruction of pancreatic beta cells as a result of various environmental factors interacting with an underlying genetic predisposition. Diabetes is a risk factor for early onset atherosclerosis, and the high mortality rate seen in these patients is partially related to cardiovascular diseases.

Objectives:

This study was conducted to compare mean platelet volume as a marker of early atherosclerosis with aortic intima-media thickness in children with type 1 diabetes and to identify its correlation with known cardiovascular risk factors.

Patients and Methods:

The study included 27 patients between age range of 6 and 17 years that were diagnosed with type 1 diabetes and 30 healthy children of the same age range who did not have any chronic disease. In both groups, we used the color Doppler ultrasound to measure children’s aortic intima-media thickness and identify their mean platelet volumes.

Results:

There was no significant difference between the groups regarding gender distribution, age, High-Density Lipoprotein (HDL) and Low-Density Lipoprotein (LDL) cholesterol levels (P > 0.05). Also no significant difference could be documented between the patient and control groups regarding the aortic intima-media thickness and mean platelet volume (P > 0.05). However, there was a significant correlation between aortic intima-media thickness and mean platelet volume (r = 0.351; P < 0.05).

Conclusions:

In the present study, there was no evidence of early atherosclerosis in children with type 1 diabetes. However, mean platelet volume having a significant correlation with aortic intima-media thickness may be useful as an early marker of atherosclerosis.     

Serum levels of soluble form of receptor for advanced glycation end products (sRAGE) are positively associated with circulating AGEs and soluble form of VCAM-1 in patients with type 2 diabetes

We have recently found that soluble form of receptor for advanced glycation end products (sRAGE) levels are positively associated with inflammatory biomarkers and the presence of coronary artery disease (CAD) in type 2 diabetic patients. Since advanced glycation end products (AGEs) up-regulate RAGE expression and endogenous sRAGE could be generated from the cleavage of cell surface RAGE, it is conceivable that sRAGE is positively associated with circulating AGEs levels in diabetes. In this study, we examined whether sRAGE were correlated to circulating levels of AGEs and soluble forms of vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) in patients with type 2 diabetes. Eighty-two Japanese type 2 diabetic patients underwent a complete history and physical examination, determination of blood chemistries, sRAGE, AGEs, sVCAM-1 and sICAM-1. Multiple regression analysis revealed that serum levels of AGEs and sVCAM-1 were independently correlated with sRAGE. This study demonstrated that serum levels of sRAGE were positively associated with circulating AGEs and sVCAM-1 levels in type 2 diabetic patients. Our present observations suggest sRAGE level may be elevated in response to circulating AGEs, thus being a novel marker of vascular injury in patients with type 2 diabetes.     

The effects of N-6 polyunsaturated fatty acid supplementation on the lipid composition and atherogenesis in mouse models of atherosclerosis

Despite numerous studies, the precise role of dietary n-6 polyunsaturated fatty acids in the pathogenesis of atherosclerosis remains controversial. It has been shown that feeding an n-6-enriched diet resulted in decreased atherosclerosis in African green monkeys and was associated with a reduction in LDL levels. However, other authors reported that n-6 supplementation increased the oxidative stress and the susceptibility of LDL to undergo in vitro oxidation, thus potentially enhancing atherosclerosis. The present study was designed to investigate the effect of dietary supplementation of n-6 polyunsaturated fats (safflower oil), as compared with a saturated fat-rich diet (Paigen), on the blood lipid profile and atherosclerosis in two mouse models. In the first experiment, female C57BL/6 mice (n=23–30 per group) were fed a cholate containing Paigen diet, a safflower oil-rich diet (with cholate), or normal chow for 15 weeks. No significant differences between the high fat diet groups were evident with respect to total cholesterol, LDL, HDL or triglyceride levels. The extent of aortic sinus fatty streaks did not differ significantly between the two groups. In the second experiment, LDL-receptor-deficient (LDL-RD) mice (n=20–30 per group) were randomized into similar dietary regimens. Mice consuming a safflower oil-enriched diet developed significantly less atherosclerosis, in comparison with Paigen diet-fed mice. A reduction in LDL levels, although not of a similar magnitude as the reduction in atherosclerosis, was evident in the safflower oil-fed mice when compared to the Paigen diet-fed littermates. In both mouse models of atherosclerosis, LDL isolated from the plasma of mice on the n-6 polyunsaturated diet was rendered slightly more susceptible to oxidation in vitro, as indicated by a shorter lag period for diene formation. Thus, the effects of n-6 fatty acids on the lipoprotein composition and other potential influences may have contributed to the anti-atherogenic effect in the LDL-RD mouse model.     

脑络通与绞股蓝总皂甙对动脉粥样硬化性疾病的疗效比较

脑络通是用来治疗动脉粥样硬化性疾病的中药复方制剂,具有滋肾养肝、消痰祛瘀作用。为明确其治疗效果,周脑络通与绞股蓝总甙对103例动脉粥样硬化性疾病患者进行两盲临床对比观察,时间5个月以上。采用美国ATL公司彩色超声多谱勒血流声象系统在用药前后探测患者两侧颈动脉粥样硬化斑块及内中膜厚度,检测患者血脂、超氧化物歧化酶、脂过氧化物和血液流变学指标,部分病人检测血小板聚集率和心功能,并检测患者的血、尿常规和肝、肾功能,观察患者临床症状。结果发现脑络通组57块颈动脉粥样硬化斑块中15.8%(9/57)的斑块消除,47.4%(27/57)的斑块减轻,29.8%(17/57)的斑块不发展,总有效率为93%(53/57);绞股蓝组分别为0%,2.8%(1/36)和47.2%(17/36),总有效率为50%(18/36).脑络通组对斑块的消除、减轻、总有效率及斑块载面积减少方面皆明显优于绞股蓝组(p<0.01或0.05)。脑络通可使增厚的内中膜减薄。在降低血总胆固醇、甘油三酯、低密度脂蛋白、升高血超氧化物歧化酶活性,降低脂过氧化物,降低全血低切粘度、纤维蛋白原、红细胞压积、血小板最大聚集率等方面皆优于绞股蓝组。提示脑络通在调血脂、抗氧化、抗血栓和改善血液流变学等方面均有作用.在临床症状和患者心脏舒缩功能的改善方面亦优于绞股蓝组.本药长期服用对患者血、尿常规,肝、肾功能无异常影响,未见明显毒副反应.说明脑络通治疗动脉粥样硬化性疾病方面疗效优于绞股蓝总皂甙,脑络通可能阻止患者动脉粥样硬化病变的发展,甚至可能使动脉粥样硬化斑块消除。