Predicting the risk of early atherosclerotic disease development in children after repair of aortic coarctation.

AIMS: Increased cardiovascular morbidity is manifested a long time after the repair of aortic coarctation (CoA). By way of impaired flow-mediated vasodilation (FMD) and increased intima media thickness (IMT), surrogate parameters of atherosclerosis, cardiovascular risk factors (RFs) can be correlated with early vascular wall changes in children. This study investigated whether changes in arterial wall function and morphology are detectable in children after coarctation repair. METHODS AND RESULTS: We examined 28 children after successful repair of CoA vs. 30 control subjects. All children underwent identical screening, with a broad RF profile and FMD/IMT measurements. CoA-children presented significantly (P < 0.001) impaired FMD (4.87 +/- 2.6 vs. 10.2 +/- 3.1%) and higher IMT values (P < 0.001) than the controls (0.48 +/- 0.08 vs. 0.38 +/- 0.05 mm). The blood pressure during rest and exercise and the left ventricular mass were significantly elevated, but no additional RF could be identified in CoA-children. Only a remaining pressure gradient related significantly to FMD. CONCLUSION: This study documents early vascular wall changes in children after successful coarctation repair. Arterial hypertension and a resting pressure gradient are the major contributing factors to early atherosclerotic development and should be primary targets for therapy. Vascular status should be monitored regularly by FMD and IMT.     

通心络抑制白细胞介素1β介导的小型猪冠状动脉早期炎症反应及内膜增殖

目的探讨通心络对白细胞介素1β介导的小型猪冠状动脉早期炎症反应及内膜增殖的抑制作用及可能机制。方法24头小型猪随机均分为假手术组、模型组和通心络组。假手术组和模型组喂养普通饲料,通心络组喂养普通饲料 通心络[1 g/(kg.d)]。2周后麻醉行左侧开胸手术,选择左前降支及回旋支近端管腔外径近似相同的两处节段进行仔细分离,假手术组在血管外膜包裹吸附生理盐水的纸巾,模型组和通心络组包裹吸附白细胞介素1β(2.5μg)的纸巾,术后继续以上喂养方法。2周后采用冠状动脉造影观察各组管腔狭窄情况。造影结束后处死动物,截取包裹血管段,进行病理学检查,并采用逆转录聚合酶链反应,测定各组手术处理血管段单核细胞趋化蛋白1、P选择素、E选择素、细胞间粘附分子1和血管细胞粘附分子1 mRNA的表达。结果冠状动脉造影显示,模型组冠状动脉管腔20%~30%狭窄,病理学检查可见模型组内膜增殖、炎性细胞浸润,平滑肌细胞内膜下迁移。通心络组管腔狭窄程度、内膜增殖及炎性细胞浸润现象较模型组明显减轻。逆转录聚合酶链反应示通心络组单核细胞趋化蛋白1、P选择素、E选择素、细胞间粘附分子1和血管细胞粘附分子1 mRNA表达强度低于模型组(P<0.05)。结论通心络对白细胞介素1β诱导的冠状动脉炎症反应及内膜增殖具有明显的抑制作用。通过抑制细胞因子和粘附因子的表达可能是其主要作用途径。     

Active but transient improvement of endothelial function in rheumatoid arthritis patients undergoing long‐term treatment with anti–tumor necrosis factor α antibody

Objective

Cardiovascular disease is the major cause of excessive mortality in rheumatoid arthritis (RA). Atherosclerosis and RA share similar inflammatory mechanisms that include involvement of tumor necrosis factor α (TNFα). Anti‐TNFα antibody improved endothelial function in RA patients after a 12‐week treatment. The aim of the present study was to assess whether improvement of endothelial function is still effective in long‐term infliximab‐treated RA patients.

Methods

Seven RA patients (5 women; age range 25–73 years) were studied. They had been treated with infliximab for at least 1 year and were currently being treated with this drug every 8 weeks. Endothelial‐dependent and independent vasodilatation were measured by brachial ultrasonography.

Results

Following infliximab infusion, a rapid increase in the percentage of endothelial‐dependent vasodilatation was found in all patients (mean ± SD 9.4 ± 5.5% 2 days postinfusion compared with 2.8 ± 2.5% 2 days before infusion). However, values returned to baseline by 4 weeks after infusion. There were no differences in the percentage of endothelial‐independent vasodilatation prior to and after infusion. A decrease in the individual disease activity score for each patient was observed at day 7 postinfusion (P = 0.02).

Conclusion

Our study confirms an active but transient effect of infliximab on endothelial function in RA patients treated periodically with this drug. It may support long‐term use of drugs that block TNFα function to reduce the high incidence of cardiovascular complications in RA.

     

Effects of dietary fish oil and butterfat on serum lipids and monocyte and platelet interactions with aortic endothelial cells

We studied effects of dietary lipids on some of the initial events in atherogenesis. Adult swine were fed low fat/low cholesterol diets, then challenged with a high cholesterol (1%, w/w) diet supplemented with 11.5% (w/w) butterfat (BF) or MaxEPA^TM fish oil (FO). Serum lipids and monocyte and platelet adhesion to porcine aortic endothelial cells in vitro were measured during feeding of the low fat diet and at 1, 2, and 5 weeks after the dietary challenge. Total cholesterol increased significantly in animals fed the BF and FO diets, but there was no difference between the groups. Animals fed FO had total cholesterol/high-density lipoprotein cholesterol values twice those fed BF ( ). After 2 weeks on the hypercholesterolemic diet, monocyte adhesion to endothelial cells increased in swine fed FO by 123% above those fed a low fat diet, and adhesion values remained elevated (56% above baseline value) after 5 weeks. Monocytes from swine fed BF showed increased adhesion by 87, 53, and 14% above those fed the low fat diet at 1, 2, and 5 weeks respectively. Platelet adhesion to endothelial cells decreased (P < 0.05) after diet change and remained low. Adhesion of platelets from swine fed FO was significantly lower than those fed BF at 1 and 2 weeks but higher at 5 weeks. The FO diet, compared to the BF diet, produced a more atherogenic cholesterol profile and greater monocyte adhesion to endothelial cells, conditions which in vivo may promote lesion initiation.     

冠心病伴肾动脉狭窄的患病率及相关因素研究

目的探讨冠心病患者中肾动脉狭窄(ARAS)的患病率及其相关因素。方法228例冠脉造影患者同时行选择性双肾动脉造影检查,对临床资料和ARAS之间的关系进行单因素和多因素Logistic回归分析。结果228例患者中,ARAS患病率为19.7%;经冠脉造影证实的152例冠心病患者中,ARAS患病率为27.6%;51例冠心病合并颈动脉粥样斑块的患者中,ARAS患病率为49.0%。45例ARAS患者中,左肾动脉狭窄的患病率显著高于右肾动脉(P<0.05)。单因素分析表明,年龄、糖尿病、肾功能不全、颈动脉粥样斑块、冠心病是ARAS的预测因素。多元Logistic回归分析表明,仅年龄、颈动脉粥样斑块、冠脉三支病变是ARAS的独立预测因素。结论对于冠心病患者,尤其是年龄≥60岁及合并颈动脉粥样斑块的患者,冠脉造影后应常规行肾动脉造影,以便早期发现ARAS。     

Coronary artery and abdominal aortic calcification are associated with cardiovascular disease in type 2 diabetes

Aims/hypothesis The goals of this study were to determine whether coronary calcium is associated with the presence of clinical cardiovascular disease in individuals with type 2 diabetes and if the measurement of abdominal aortic calcium may have an independent or added benefit as a surrogate marker for clinical vascular disease.Methods A cross-sectional study of subjects with type 2 diabetes enrolled in seven medical centres in the USA participating in a Veterans Affairs Cooperative Study of glycaemic control. Enrolled subjects included 309 veterans over 40 years of age with type 2 diabetes, with or without stable cardiovascular disease, who had inadequate glycaemic control (HbA₁c>7.5%) on oral agents and/or insulin. The study assessed lifestyle behaviours, standard cardiovascular risk factors and coronary artery and abdominal aorta calcification by electron beam computed tomography.Results Subjects with coronary artery or abdominal aorta calcification present had a strikingly higher prevalence of peripheral artery disease, coronary artery disease and all combined cardiovascular disease. Prevalence of each condition increased from 5- to 13-fold with increasing quintiles of coronary artery calcification and from 2- to 3-fold with increasing abdominal aorta calcification. These associations persisted after adjustment for lifestyle behaviours and standard cardiovascular risk factors.Conclusions/interpretation These results support the notion that vascular calcium in type 2 diabetes provides additional information beyond that of standard risk factors in identifying the presence of cardiovascular disease. Subclinical measures of atherosclerosis such as arterial calcification may help more precisely stratify these individuals and alert healthcare providers to those individuals who have particularly accelerated atherosclerosis.     

P38信号通路对人脐静脉内皮细胞单核细胞趋化蛋白-1表达的影响

目的 探讨P38信号通路(P38MAPK)和单核细胞趋化蛋白-1(MCP-1)的关系，以及P38MAPK在糖尿病(DM)动脉粥样硬化(AS)中的作用。方法 分别以高葡萄糖(HG)、糖基化终产物(AGEs)、高胰岛素(HIns)和过氧化氢(H2O2)孵育人脐静脉内皮细胞(HUVECs)，观察HUVECs P38MAPK的蛋白表达和MCP-1 mRNA表达；以P38MAPK特异抑制剂SB203580预处理，再用以上4种刺激因素孵育HUVECs，观察MCP-1 mRNA在HUVECs的表达。结果 HG、AGEs、HIns和H2O2均可独立激活P38MAPK，使磷酸化P38MAPK蛋白表达量及MCP-1 mRNA表达量增加；SB203580预处理后，MCP-1 mRNA表达被明显抑制。结论 P38MAPK调控MCP-1的表达，表明P38MAPK可能是DM致AS发生的始动信号之一。     

调肝导浊中药对血载脂蛋白含量及肝细胞膜脂蛋白受体的影响

为观察调肝导浊中药对血载脂蛋白的含量及肝细胞膜脂蛋白受体的影响。采用高胆固醇饮食造成动脉粥样硬化家兔模型，用免疫比浊法测定载脂蛋白AI和载脂蛋白B含量，体外培养大鼠肝细胞，将氧化型低密度脂蛋白直接加入培养液，采用原位杂交技术观察它对肝细胞膜脂蛋白受体的影响及调肝导浊中药对其的调节作用。结果发现，调肝导浊中药可有效升高载脂蛋白AI含量和降低载脂蛋白B含量，提示调肝导浊中药对脂蛋白受体途径具有良好的调节作用，可有效调节与脂质代谢密切相关的因素。从而防治高脂血症，抑制动脉粥样硬化的形成发展。     

雌激素对高胆固醇血症兔动脉粥样硬化形成的影响研究

3组纯种新西兰雌兔，A组为去卵巢未补充雌激素，B组去卵巢补充雌激素，C组未切除卵巢，均给1％胆固醇饮食。8周后取主动脉行内膜扫描电镜及光镜观察。A组主动脉内膜明显增厚、横断面内膜面积明显增高（P＜0．01）、泡沫细胞相对较多（与B、C组比较），A组低密度脂蛋白胆固醇明显高于B组（P＜005），余血脂水平3组间无统计学差异。结果提示雌激素可抑制高胆固醇血症兔动脉粥样硬化的形成。     

原发性高血压患者缺血性脑血管病与颈动脉粥样硬化及碱性成纤维细胞生长因子的关系

目的探讨原发性高血压患者缺血性脑血管病与颈动脉粥样硬化及碱性成纤维细胞生长因子之间的关系及临床意义。方法采用惠普彩色多普勒仪测定颈动脉,观察颈总动脉、颈内动脉和颈动脉分叉部的图像。采用酶联免疫吸附试验方法测定外周血中碱性成纤维细胞生长因子。结果与高血压不伴缺血性脑血管病组比,高血压伴缺血性脑血管病组碱性成纤维细胞生长因子水平(364.5±91.0mg/L比283.4±91.2mg/L)、软斑检出率(92.3%比52.4%)和右侧颈内动脉收缩期峰值流速(57.65±7.34mm/s比52.41±7.97mm/s)均显著升高(P<0.05或0.01);软斑组碱性成纤维细胞生长因子水平比硬斑组明显升高(319.7±93.6mg/L比252.2±77.9mg/L,P<0.05)。结论碱性成纤维细胞生长因子和动脉粥样硬化斑块的形成在高血压缺血性脑血管病的发生发展过程中起重要作用,对判别高血压病变的程度、预防脑梗死提供了重要依据,有利于临床采取正确的干预治疗措施。