• 【胆固醇晶体,平滑肌细胞和动脉粥样硬化发生的新数据。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Kiyak JH
    BACKGROUND & AIMS: The histologic appearance of atherosclerosis has been well described but its pathogenesis is still vigorously debated. The purpose of the present study is to clarify the stimuli for smooth muscle cells (SMC) migration and proliferation as well as the way of cholesterol crystals (CC) generation. We performed postmortem ultrastructural analysis of myocardial samples obtained from 45 patients (33 males, 12 females, age range 18-85) who died from different diseases, mainly from acute myocardial infarction-MI (37 cases). Tissue was taken by transthorax express-necropsy method immediately after patients' death in the clinic. In myocardial infarction cases intact zones of the heart were examined. We have found a few foci of modified SMC proliferation in the periarteriolar space around necrotic cellular debris in elder patients. Lymphocytes, myofibroblasts and some leukocytes infiltrated those areas. The modified SMC phagocyted necrotic material and formed secondary lysosomes, inside which from one to three CC originated. In parallel with the reduction of necrotic mass inside the lysosomes, CC size increased. In the final phase the CC were discharged from the SMC into the interstitium. After exocytosis a tendency for the CC to accumulate was observed. They formed clusters consisting of 20-30 crystals. Most of the CC were of typical needle-like or rhomboid shape. Modified SMC were producing not only CC but also collagen and elastin. This study indicates that atherosclerotic process in the myocardium is connected with the appearance of modified SMC inside which CC are generated.

    背景与目标: 动脉粥样硬化的组织学表现已得到很好的描述,但其发病机理仍在激烈辩论中。本研究的目的是阐明平滑肌细胞 (SMC) 迁移和增殖的刺激以及胆固醇晶体 (CC) 产生的方式。我们对45例死于不同疾病的患者 (男33例,女12例,年龄18-85岁) 的心肌样本进行了死后超微结构分析,这些患者主要死于急性心肌梗死 (MI) (37例)。患者在诊所死亡后,立即通过经胸快速尸检方法采集组织。在心肌梗塞病例中,检查了心脏的完整区域。我们在老年患者坏死细胞碎片周围的小动脉周围发现了一些SMC增殖的病灶。淋巴细胞、肌成纤维细胞和一些白细胞浸润这些区域。修饰的SMC吞噬了坏死物质,并形成了次级溶酶体,在其中产生了一到三个CC。与溶酶体内坏死质量减少同时,CC大小增加。在最后阶段,CC从SMC排放到间质中。胞吐后,观察到CC积累的趋势。他们形成了由20-30个晶体组成的簇。大多数CC为典型的针状或菱形形状。改性SMC不仅产生CC,还产生胶原蛋白和弹性蛋白。这项研究表明,心肌中的动脉粥样硬化过程与内部产生CC的改良SMC的出现有关。
  • 【类风湿性关节炎患者血清骨保护素升高,并与冠状动脉粥样硬化独立相关。】 复制标题 收藏 收藏
    DOI:10.1016/j.atherosclerosis.2007.04.049 复制DOI
    作者列表:Asanuma Y,Chung CP,Oeser A,Solus JF,Avalos I,Gebretsadik T,Shintani A,Raggi P,Sokka T,Pincus T,Stein CM
    BACKGROUND & AIMS: :Osteoprotegerin (OPG), a soluble decoy receptor for receptor activator of nuclear factor kappaB ligand, is implicated in the pathogenesis of atherosclerosis. Patients with rheumatoid arthritis (RA) have inflammation and increased atherosclerosis. We examined the hypothesis that OPG concentrations are increased in patients with RA and are associated with coronary-artery atherosclerosis. Serum OPG concentrations were measured by ELISA and coronary-artery calcification by electron-beam computer tomography in 157 patients with RA and 87 control subjects. OPG concentrations were higher in patients with long-standing RA (n=67) [median (interquartile range)]: [1895 (1337-2847) pg/mL, and early RA (n=90): [1340 (1021-1652) pg/mL, than controls 1068 (692-1434) pg/mL; (p<0.001)]. In patients with RA, OPG concentrations were associated with erythrocyte sedimentation rate (p<0.001), homocysteine (p=0.001), disease duration (p=0.02), coronary calcium score (p=0.03), and cumulative dose of corticosteroids (p=0.04) after adjustment for age and sex. In patients with long-standing RA, OPG was associated with coronary-artery calcification independently of cardiovascular risk factors and disease activity [OR for every increase in 500 pg/mL of OPG=2.22 (1.43-3.34), p<0.001]. In conclusion, OPG concentrations are increased in patients with RA and are associated with inflammation. In patients with long-standing disease, OPG is independently associated with coronary-artery calcification.
    背景与目标: 骨保护素 (OPG) 是核因子kappaB配体受体激活剂的可溶性诱饵受体,与动脉粥样硬化的发病机理有关。类风湿性关节炎 (RA) 患者有炎症和动脉粥样硬化增加。我们研究了以下假设: RA患者OPG浓度升高并与冠状动脉粥样硬化相关。通过ELISA测量血清OPG浓度,并通过电子束计算机断层扫描测量157例RA患者和87例对照受试者的冠状动脉钙化。长期RA患者的OPG浓度较高 (n = 67) [中位数 (四分位间距)]: [1895 (1337-2847) pg/mL,而早期RA (n = 90): [1340 (1021-1652) pg/mL,比对照组1068 (692-1434) pg/mL; (p<0.001)].在RA患者中,OPG浓度与红细胞沉降率 (p<0.001) 、同型半胱氨酸 (p = 0.001) 、病程 (p = 0.02) 、校正年龄和性别后,冠状动脉钙化评分 (p = 0.03) 和皮质类固醇的累积剂量 (p = 0.04)。OPG与冠状动脉钙化无关,独立于心血管危险因素和疾病活动 [或每增加500 pg/mL OPG = 2.22 (1.43-3.34),p<0.001]。在RA患者中,OPG浓度升高并与炎症相关。在长期存在疾病的患者中,OPG与冠状动脉钙化独立相关。
  • 【臭氧氧化预处理可防止新西兰白兔动脉粥样硬化的发展。】 复制标题 收藏 收藏
    DOI:10.1097/FJC.0b013e31827a820d 复制DOI
    作者列表:Delgado-Roche L,Martínez-Sánchez G,Re L
    BACKGROUND & AIMS: :Atherosclerosis is a major cause of death in the Western World. It is known that Lipofundin 20% induces atherosclerotic lesions, whereas ozone at low doses has been satisfactorily used in the prevention of oxidative stress-associated pathologies, such as coronary artery diseases. The aim of the present work was to evaluate the effects of ozone therapy on Lipofundin-induced atherosclerotic lesions in New Zealand White rabbits. Ozone (1 mg), mixed with oxygen as passive carrier, was administered by rectal insufflation during 15 sessions in 5 weeks. Then, the animals were intravenously treated with 2 mL/kg of Lipofundin, daily during 8 days. Animals were euthanized and eosin and hematoxylin staining was used for aortic histopathological analysis. The biomarkers of oxidative stress and lipid profile in serum were determined by spectrophotometric techniques. The results demonstrated that ozone induced inhibitory effects on aortic lesions formation. On the other hand, a reduction of biomolecular damage and an increase of antioxidant systems were observed at the end of the experiment. The serum lipids profiles were not modified after only 1 cycle of ozone treatment. Our results reinforced the hypotheses that antioxidant effects induced by ozone in the context of atherosclerosis demonstrate the antiatherogenic properties of the gas in the experimental conditions of this study.
    背景与目标: : 动脉粥样硬化是西方世界的主要死亡原因。已知Lipofundin 20% 诱导动脉粥样硬化病变,而低剂量的臭氧已令人满意地用于预防与氧化应激相关的病变,例如冠状动脉疾病。本工作的目的是评估臭氧疗法对新西兰白兔Lipofundin诱导的动脉粥样硬化病变的影响。臭氧 (1 mg) 与氧气混合,作为被动载体,在5周内的15个疗程中通过直肠吹气给药。然后,在8天内每天用2 ml/kg的Lipofundin静脉内治疗动物。对动物进行安乐死,并使用曙红和苏木精染色进行主动脉组织病理学分析。通过分光光度法测定血清中氧化应激和脂质谱的生物标志物。结果表明,臭氧对主动脉病变的形成具有抑制作用。另一方面,在实验结束时观察到生物分子损伤的减少和抗氧化系统的增加。仅经过1个臭氧处理周期后,血清脂质谱没有改变。我们的结果强化了以下假设: 在动脉粥样硬化的背景下,臭氧诱导的抗氧化作用证明了在本研究的实验条件下气体的抗动脉粥样硬化特性。
  • 【五指山小型猪近交系高胆固醇高脂饮食诱导的动脉粥样硬化。】 复制标题 收藏 收藏
    DOI:10.1080/10495398.2017.1322974 复制DOI
    作者列表:Zhao Y,Xiang L,Liu Y,Niu M,Yuan J,Chen H
    BACKGROUND & AIMS: :Coronary artery disease has a significant genetic predisposition, which mainly results from atherosclerosis. Miniature pig is an excellent model to investigate atherosclerosis. This study investigated whether the occurrence and development of atherosclerosis in the Wuzhishan miniature pigs (WZSPs) that were closely bred 12 generations had better consistency. The WZSPs (n = 9) were fed a high-cholesterol and high-fat diet (HCFD). After continuous feeding, 3 WZSPs each were sacrificed at 6, 8, and 12 months, respectively, and the general clinical manifestations and serological indexes were detected. The pathological changes of the major arteries and main organs were recorded. The results showed WZSPs were quite susceptible to the HCFD. At 6 months, plaque lesions appeared in the abdominal aorta and iliac artery, while at 8 months, they appeared in the coronary artery. At 12 months, atherosclerotic lesions could be found in all major arteries, while lipid core, cholesterol precipitation, and calcium deposition appeared in the most serious sites. The progression of arterial lesions and distribution of the lesions were highly consistent in the pigs. However, apparent variations in serum markers were observed. In conclusion, inbred WZSP is a good model to investigate atherosclerosis and has good predictability for the occurrence and development of the disease.
    背景与目标: 冠状动脉疾病具有显著的遗传易感性,这主要是由动脉粥样硬化引起的。小型猪是研究动脉粥样硬化的极好模型。本研究调查了近育12代的五指山小型猪 (WZSPs) 动脉粥样硬化的发生和发展是否具有较好的一致性。WZSPs (n   =   9) 采用高胆固醇和高脂肪饮食 (HCFD)。连续喂养后,分别于6、8和12个月处死3个WZSPs,并检测其一般临床表现和血清学指标。记录主要动脉和主要器官的病理变化。结果表明,wzsp对HCFD非常敏感。6个月时,腹主动脉和髂动脉出现斑块病变,8个月时,冠状动脉出现斑块病变。在12个月时,所有主要动脉均可发现动脉粥样硬化病变,而脂质核心,胆固醇沉淀和钙沉积出现在最严重的部位。在猪中,动脉病变的进展和病变的分布高度一致。然而,观察到血清标志物的明显变化。总之,近交WZSP是研究动脉粥样硬化的良好模型,对疾病的发生和发展具有良好的可预测性。
  • 【氯吡格雷前负荷方案对动脉粥样硬化患者阿司匹林的急性抗血栓作用。】 复制标题 收藏 收藏
    DOI:10.1161/01.atv.20.10.2316 复制DOI
    作者列表:Helft G,Osende JI,Worthley SG,Zaman AG,Rodriguez OJ,Lev EI,Farkouh ME,Fuster V,Badimon JJ,Chesebro JH
    BACKGROUND & AIMS: :There is a need for a rapid antithrombotic effect after the administration of antiplatelet drugs in the setting of acute coronary syndromes and percutaneous interventions. Clopidogrel, a new thienopyridine derivative, is an efficient antiplatelet agent. However, the standard regimen of clopidogrel (75 mg/d) requires 2 to 3 days before significant antithrombotic effects. Patients with stable arterial disease on chronic aspirin therapy (n=20) were treated with clopidogrel either with a front-loaded regimen, 300 mg the first day and 75 mg/d the next 7 days, or with a standard regimen, 75 mg/d for 8 days. Blood thrombogenicity was assessed by quantification of platelet-thrombus formation in an ex vivo perfusion chamber, by ADP-induced platelet aggregation, and by ADP-induced fibrinogen binding. At 2 hours, mean total thrombus area with the standard regimen was not significantly reduced. In contrast, at 2 hours, the mean total thrombus area with the front-loaded regimen was significantly decreased by 23.1+/-8.5% versus baseline (P<0.05). ADP-induced platelet aggregation (with 5 and 10 micromol/L) was also significantly (P<0.05) reduced with the front-loaded regimen at 2 hours, with the mean platelet aggregation being 82.2+/-4.4% and 81.8+/-4.5%, respectively, versus baseline. Similarly, flow cytometry demonstrated a significant decrease (P<0. 05) in the ADP-induced fibrinogen binding (with 0.12 and 0.6 micromol/L) at 2 hours in this front-loaded regimen group (36.1+/-2. 0% and 53.2+/-9.3%). With the standard regimen, platelet activity was not significantly reduced at 2 hours. Our data suggest that a front-loaded regimen of clopidogrel added to aspirin achieves a significant antithrombotic effect at 2 hours in patients with known atherosclerotic disease on chronic aspirin therapy. This provides a rationale for using front-loaded clopidogrel in combination with aspirin in percutaneous coronary interventions.
    背景与目标: : 在急性冠状动脉综合征和经皮介入治疗的情况下,使用抗血小板药物后需要快速的抗血栓形成作用。氯吡格雷是一种新的噻吩吡啶衍生物,是一种有效的抗血小板药物。然而,氯吡格雷的标准方案 (75 mg/d) 需要2至3天才能产生明显的抗血栓形成作用。接受慢性阿司匹林治疗 (n = 20) 的稳定动脉疾病患者接受氯吡格雷治疗,采用前负荷方案,第一天300 mg,接下来7天75 mg/d,或者采用标准方案,75 mg/d,持续8天。通过量化离体灌注室中的血小板-血栓形成,ADP诱导的血小板聚集和ADP诱导的纤维蛋白原结合来评估血液的血栓形成性。2小时时,标准方案的平均总血栓面积没有明显减少。相反,在2小时时,与基线相比,前负荷方案的平均总血栓面积显着减少了23.1/-8.5% (P<0.05)。ADP诱导的血小板聚集 (5和10微摩尔/升) 也显著降低 (P<0.05),前负荷方案在2小时,平均血小板聚集分别为82.2 +/-4.4% 和81.8 +/-4.5%,与基线相比。类似地,流式细胞术显示ADP诱导的纤维蛋白原结合 (0.12和0.6 micromol/L) 在2小时前加载方案组 (36.1 +/-2. 0% 和53.2 +/-9.3%) 显着降低 (P <0.05)。在标准方案中,血小板活性在2小时没有明显降低。我们的数据表明,在阿司匹林中加入氯吡格雷的前负荷方案在接受慢性阿司匹林治疗的已知动脉粥样硬化疾病的患者中,在2小时内可获得显着的抗血栓形成作用。这为在经皮冠状动脉介入治疗中使用前载氯吡格雷与阿司匹林联合提供了依据。
  • 【使用DPP-4抑制剂预防糖尿病动脉粥样硬化试验的原理,设计和基线特征: 阿格列汀对糖尿病动脉粥样硬化 (SPEAD-a) 的预防作用研究。】 复制标题 收藏 收藏
    DOI:10.5551/jat.18333 复制DOI
    作者列表:
    BACKGROUND & AIMS: AIM:Alogliptin, an efficacious inhibitor of DPP-4 that improves glycemic control, as well as the pancreatic beta-cell function, is now increasingly used to accomplish glycemic targets in type 2 diabetic patients. Interestingly, recent experimental studies have shown that alogliptin exerts anti-atherosclerotic effects in GLP-1-dependent and -independent manners. The aim of the present ongoing study is to investigate the preventive effects of alogliptin on the progression of atherosclerosis in type 2 diabetic subjects using the carotid intima-media thickness (IMT), an established marker of cardiovascular disease. METHODS AND RESULTS:The Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A) is a prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group, comparative study. Between March 2011 and March 2012, 341 participants were recruited at 11 clinical sites, and were randomly allocated either to an alogliptin treatment group (172 patients) or a conventional treatment group (169 patients). The primary outcomes are the changes in the maximum and mean IMT of the common carotid artery during a 24-month treatment period, as measured by carotid arterial echography. The secondary outcomes include the changes in glycemic control, parameters related to beta-cell function and diabetic nephropathy, the occurrence of cardiovascular events and adverse events and biochemical measurements reflecting vascular function. CONCLUSIONS:This is the first study to address the effects of DPP-4 inhibitors on the progression of changes in the carotid IMT, with the patients without DPP-4 inhibitor treatment serving as a control group. The results will be available soon, and these findings are expected to provide clinical data that will be helpful in the prevention of diabetic atherosclerosis and subsequent cardiovascular disease.
    背景与目标:
  • 【左,右,近或远壁颈总动脉内膜中层厚度测量: 与心血管疾病和下肢动脉粥样硬化的关系。】 复制标题 收藏 收藏
    DOI:10.1016/s0895-4356(97)00059-0 复制DOI
    作者列表:Bots ML,de Jong PT,Hofman A,Grobbee DE
    BACKGROUND & AIMS: :We evaluated the differences in strength of the associations of prevalent cardiovascular disease and lower extremity arterial atherosclerosis to common carotid intima-media thickness, assessed by near wall measurements only, by far wall measurements only, and by the average of near and far wall measurements. The study was based on data from 1500 participants of the Rotterdam Study, a single-center-population-based prospective follow-up study among 7983 subjects, aged 55 years or over. Comparison of the strength of the associations of near wall intima-media thickness and of combined near and far wall intima-media thickness to cardiovascular disease and lower extremity arterial atherosclerosis revealed significantly stronger associations compared to associations observed for far wall intima-media thickness, in particular for stroke and lower extremity arterial disease. We conclude that near wall common carotid intima-media thickness measurement provides at least as good an indicator of atherosclerosis elsewhere and of cardiovascular risk as the far wall intima-media thickness measurement.
    背景与目标: : 我们评估了流行的心血管疾病和下肢动脉粥样硬化与颈总动脉内膜中层厚度的相关性的强度差异,仅通过近壁测量,仅通过远壁测量以及近壁和远壁测量的平均值来评估。该研究基于鹿特丹研究的1500名参与者的数据,该研究是一项基于单中心人群的前瞻性随访研究,涉及7983名年龄在55岁或以上的受试者。比较近壁内膜-中膜厚度以及近壁和远壁内膜-中膜厚度与心血管疾病和下肢动脉粥样硬化的相关性,发现与观察到的远壁内膜-中膜厚度的相关性相比,相关性明显更强,特别是对于中风和下肢动脉疾病。我们得出的结论是,近壁颈总动脉内膜中层厚度的测量至少与远壁内膜中层厚度的测量一样,可以很好地指示其他地方的动脉粥样硬化和心血管风险。
  • 【直接输注骨髓源性祖细胞和间接动员造血祖细胞对动脉粥样硬化斑块和炎症过程的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.ijcard.2013.07.229 复制DOI
    作者列表:Tousoulis D,Briasoulis A,Vogiatzi G,Valatsou A,Kourkouti P,Pantopoulou A,Papageorgiou N,Perrea D,Stefanadis C
    BACKGROUND & AIMS: BACKGROUND:We sought to investigate the effects of lin-/sca+ cells, endothelial progenitor cells (EPCs) and granulocyte colony-stimulating factor (G-CSF) administration on atherosclerotic plaque progression. METHODS:Apolipoprotein E-deficient (apoE(-/-)) mice were splenectomized and treated with high-cholesterol diet for 6 weeks in order to induce atherosclerotic plaque development. Bone marrow-derived Lin-/sca-1+ cells were isolated and further cultured to early growth endothelial progenitor cells (EPCs). Mice were divided in four groups (n=10/group) and received two intravenous injections of 5×10(5) cells (lin-/sca-1+ or EPCs), or granulocyte colony-stimulating factor (G-CSF 100 μg/kg/day) for 7 days or normal saline. The same interventions were administered to animals, which had undergone unilateral hind-limb ischemia. Effects on inflammatory parameters, lesion severity, and atherosclerotic plaque area size were assessed. RESULTS:The administration of both G-CSF and progenitor cells significantly decreased the levels of IL-6, 6 weeks after the initiation of treatment. Atherosclerotic lesion area was reduced by G-CSF (atherosclerotic plaque area percentage 22.94%±3.68, p=0.001), by lin-/sca-1+ (23.27%±5.98, p=0.002) and cultured EPCs (23.16±4.86%, p=0.002) compared to control (32.75%±7.05). In the atherosclerotic mice that underwent limb ischemia, the atherosclerotic plaque area, was not significantly different between the treatment groups cultured EPCs-treated mice and the control group (p=NS, for all). CONCLUSIONS:Direct infusion of progenitor cells and indirect mobilization of hematopoietic progenitor cells decreased plaque progression and levels of inflammatory molecules in a murine model of atherosclerosis. Treatment with G-CSF, lin-/sca-1+, or EPCs may exert beneficial effects on vascular inflammation and atherosclerotic plaque progression. However, the effects are diminished in an ischemic setting.
    背景与目标:
  • 【冠心病的多基因风险通过2型糖尿病的动脉粥样硬化起作用。】 复制标题 收藏 收藏
    DOI:10.1186/s12933-020-0988-9 复制DOI
    作者列表:Lu T,Forgetta V,Yu OHY,Mokry L,Gregory M,Thanassoulis G,Greenwood CMT,Richards JB
    BACKGROUND & AIMS: BACKGROUND:Type 2 diabetes increases the risk of coronary heart disease (CHD), yet the mechanisms involved remain poorly described. Polygenic risk scores (PRS) provide an opportunity to understand risk factors since they reflect etiologic pathways from the entire genome. We therefore tested whether a PRS for CHD influenced risk of CHD in individuals with type 2 diabetes and which risk factors were associated with this PRS. METHODS:We tested the association of a CHD PRS with CHD and its traditional clinical risk factors amongst individuals with type 2 diabetes in UK Biobank (N = 21,102). We next tested the association of the CHD PRS with atherosclerotic burden in a cohort of 352 genome-wide genotyped participants with type 2 diabetes who had undergone coronary angiograms. RESULTS:In the UK Biobank we found that the CHD PRS was strongly associated with CHD amongst individuals with type 2 diabetes (OR per standard deviation increase = 1.50; p = 1.5 × 10- 59). But this CHD PRS was, at best, only weakly associated with traditional clinical risk factors, such as hypertension, hyperlipidemia, glycemic control, obesity and smoking. Conversely, in the angiographic cohort, the CHD PRS was strongly associated with multivessel stenosis (OR = 1.65; p = 4.9 × 10- 4) and increased number of major stenotic lesions (OR = 1.35; p = 9.4 × 10- 3). CONCLUSIONS:Polygenic predisposition to CHD is strongly associated with atherosclerotic burden in individuals with type 2 diabetes and this effect is largely independent of traditional clinical risk factors. This suggests that genetic risk for CHD acts through atherosclerosis with little effect on most traditional risk factors, providing the opportunity to explore new biological pathways.
    背景与目标:
  • 【IgE通过影响巨噬细胞极化,巨噬细胞蛋白网络和泡沫细胞形成而导致动脉粥样硬化和肥胖。】 复制标题 收藏 收藏
    DOI:10.1161/ATVBAHA.119.313744 复制DOI
    作者列表:Zhang X,Li J,Luo S,Wang M,Huang Q,Deng Z,de Febbo C,Daoui A,Liew PX,Sukhova GK,Metso J,Jauhiainen M,Shi GP,Guo J
    BACKGROUND & AIMS: OBJECTIVE:By binding to its high-affinity receptor FcεR1, IgE activates mast cells, macrophages, and other inflammatory and vascular cells. Recent studies support an essential role of IgE in cardiometabolic diseases. Plasma IgE level is an independent predictor of human coronary heart disease. Yet, a direct role of IgE and its mechanisms in cardiometabolic diseases remain incompletely understood. Approach and Results: Using atherosclerosis prone Apoe-/- mice and IgE-deficient Ige-/- mice, we demonstrated that IgE deficiency reduced atherosclerosis lesion burden, lesion lipid deposition, smooth muscle cell and endothelial cell contents, chemokine MCP (monocyte chemoattractant protein)-1 expression and macrophage accumulation. IgE deficiency also reduced bodyweight gain and increased glucose and insulin sensitivities with significantly reduced plasma cholesterol, triglyceride, insulin, and inflammatory cytokines and chemokines, including IL (interleukin)-6, IFN (interferon)-γ, and MCP-1. From atherosclerotic lesions and peritoneal macrophages from Apoe-/-Ige-/- mice that consumed an atherogenic diet, we detected reduced expression of M1 macrophage markers (CD68, MCP-1, TNF [tumor necrosis factor]-α, IL-6, and iNOS [inducible nitric oxide synthase]) but increased expression of M2 macrophage markers (Arg [arginase]-1 and IL-10) and macrophage-sterol-responsive-network molecules (complement C3, lipoprotein lipase, LDLR [low-density lipoprotein receptor]-related protein 1, and TFR [transferrin]) that suppress macrophage foam cell formation. These IgE activities can be reproduced in bone marrow-derived macrophages from wild-type mice, but muted in cells from FcεR1-deficient mice, or blocked by anti-IgE antibody or complement C3 deficiency. CONCLUSIONS:IgE deficiency protects mice from diet-induced atherosclerosis, obesity, glucose tolerance, and insulin resistance by regulating macrophage polarization, macrophage-sterol-responsive-network gene expression, and foam cell formation.
    背景与目标:
  • 【中性粒细胞微泡通过将miR-155递送至动脉粥样硬化内皮来驱动动脉粥样硬化。】 复制标题 收藏 收藏
    DOI:10.1038/s41467-019-14043-y 复制DOI
    作者列表:
    BACKGROUND & AIMS: :Neutrophils are implicated in the pathogenesis of atherosclerosis but are seldom detected in atherosclerotic plaques. We investigated whether neutrophil-derived microvesicles may influence arterial pathophysiology. Here we report that levels of circulating neutrophil microvesicles are enhanced by exposure to a high fat diet, a known risk factor for atherosclerosis. Neutrophil microvesicles accumulate at disease-prone regions of arteries exposed to disturbed flow patterns, and promote vascular inflammation and atherosclerosis in a murine model. Using cultured endothelial cells exposed to disturbed flow, we demonstrate that neutrophil microvesicles promote inflammatory gene expression by delivering miR-155, enhancing NF-κB activation. Similarly, neutrophil microvesicles increase miR-155 and enhance NF-κB at disease-prone sites of disturbed flow in vivo. Enhancement of atherosclerotic plaque formation and increase in macrophage content by neutrophil microvesicles is dependent on miR-155. We conclude that neutrophils contribute to vascular inflammation and atherogenesis through delivery of microvesicles carrying miR-155 to disease-prone regions.
    背景与目标: 中性粒细胞与动脉粥样硬化的发病机制有关,但很少在动脉粥样硬化斑块中检测到。我们调查了中性粒细胞来源的微泡是否会影响动脉病理生理学。在这里,我们报告了通过暴露于高脂饮食 (一种已知的动脉粥样硬化危险因素) 来提高循环中性粒细胞微泡的水平。中性粒细胞微泡在暴露于紊乱血流模式的动脉易患病区域积聚,并在鼠模型中促进血管炎症和动脉粥样硬化。使用暴露于扰动流的培养的内皮细胞,我们证明中性粒细胞微泡通过递送miR-155促进炎症基因表达,增强NF-κ b活化。同样,中性粒细胞微泡增加miR-155,并在体内流动紊乱的易发部位增强NF-κ b。中性粒细胞微泡对动脉粥样硬化斑块形成的增强和巨噬细胞含量的增加取决于miR-155。我们得出的结论是,中性粒细胞通过将携带miR-155的微泡递送到易患疾病的区域而导致血管炎症和动脉粥样硬化。
  • 【阿托伐他汀对不同小鼠动脉粥样硬化模型的内皮标志物有明显的影响。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Nachtigal P,Jamborova G,Pospisilova N,Pospechova K,Solichova D,Zdansky P,Semecky V
    BACKGROUND & AIMS: PURPOSE:Atherosclerosis is a progressive process that initially involves endothelial dysfunction. We investigated the effects of atorvastatin on both lipid parameters, and VCAM-1 and ICAM-1 expression in apoE-deficient or wild type C57BL/6J mice. METHODS:The C57BL/6J mice were fed with either chow or an atherogenic diet for 12 weeks. Male apoE-deficient mice were fed with the chow diet for 12 weeks. In 3 atorvastatin treated groups mice were fed the same diet as described above except atorvastatin was added to the diet at the dosage of 10 mg/kg per day for the last 8 weeks before euthanasia. RESULTS:Biochemical analysis showed that atorvastatin significantly decreased total cholesterol levels and VLDL in C57BL/6J mice fed with atherogenic diet but increased serum lipid levels in apoE-deficient mice. Stereological analysis of the immunohistochemical staining revealed that atorvastatin reduced endothelial expression of ICAM-1 and VCAM-1 only in C57BL/6J mice on chow diet. CONCLUSION:We have demonstrated that endothelial expression of both VCAM-1 and ICAM-1 does not correlate with cholesterol levels in these mice. Moreover, we showed that 8-week administration of atorvastatin decrease endothelial expression of VCAM-1 and ICAM-1 in C57BL/6J wild type mice beyond its lipid lowering effect but not in C57BL/6J wild type mice fed by atherogenic diet or in apoE-deficient mice.
    背景与目标:
  • 【持续光照的昼夜节律破坏会加剧雄性载脂蛋白缺乏小鼠的动脉粥样硬化。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-020-66834-9 复制DOI
    作者列表:Chalfant JM,Howatt DA,Tannock LR,Daugherty A,Pendergast JS
    BACKGROUND & AIMS: :Disruption of the circadian system caused by disordered exposure to light is pervasive in modern society and increases the risk of cardiovascular disease. The mechanisms by which this happens are largely unknown. ApolipoproteinE-deficient (ApoE-/-) mice are studied commonly to elucidate mechanisms of atherosclerosis. In this study, we determined the effects of light-induced circadian disruption on atherosclerosis in ApoE-/- mice. We first characterized circadian rhythms of behavior, light responsiveness, and molecular timekeeping in tissues from ApoE-/- mice that were indistinguishable from rhythms in ApoE+/+ mice. These data showed that ApoE-/- mice had no inherent circadian disruption and therefore were an appropriate model for our study. We next induced severe disruption of circadian rhythms by exposing ApoE-/- mice to constant light for 12 weeks. Constant light exposure exacerbated atherosclerosis in male, but not female, ApoE-/- mice. Male ApoE-/- mice exposed to constant light had increased serum cholesterol concentrations due to increased VLDL/LDL fractions. Taken together, these data suggest that ApoE-/- mice are an appropriate model for studying light-induced circadian disruption and that exacerbated dyslipidemia may mediate atherosclerotic lesion formation caused by constant light exposure.
    背景与目标: : 在现代社会中,由于光线的紊乱而引起的昼夜节律系统的破坏普遍存在,并增加了患心血管疾病的风险。发生这种情况的机制在很大程度上是未知的。载脂蛋白缺乏 (ApoE-/-) 小鼠通常被研究以阐明动脉粥样硬化的机制。在这项研究中,我们确定了光诱导的昼夜节律破坏对ApoE-/-小鼠动脉粥样硬化的影响。我们首先表征了ApoE-/-小鼠组织中行为的昼夜节律,光反应性和分子计时,这些节律与ApoE/小鼠的节律没有区别。这些数据表明ApoE-/-小鼠没有固有的昼夜节律破坏,因此是我们研究的合适模型。接下来,我们通过将ApoE-/-小鼠暴露于持续的光照下12周,导致昼夜节律的严重破坏。持续的光照会加剧雄性ApoE-/-小鼠的动脉粥样硬化,但不是雌性。由于VLDL/LDL分数增加,暴露于恒定光下的雄性ApoE-/-小鼠的血清胆固醇浓度增加。综上所述,这些数据表明ApoE-/-小鼠是研究光诱导的昼夜节律破坏的合适模型,并且加剧的血脂异常可能介导由持续的光照引起的动脉粥样硬化病变的形成。
  • 【内皮功能障碍和进行性冠状动脉粥样硬化: 在具有多种心脏危险因素的患者中的序贯侵入性研究。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Chander R,Kuhner PA,Laws Houghton J
    BACKGROUND & AIMS: :This manuscript describes sequential angiographic, endothelial and vasoreactivity characteristics of the coronary arterial circulation in a middle-aged patient with multiple cardiac risk factors who developed hemodynamically significant coronary atherosclerosis over a 6-year period. A 56-year-old woman demonstrated marked angiographic progression of coronary atherosclerosis over time beginning with minor luminal irregularities in the setting of severe endothelial dysfunction. The association of endothelial dysfunction, ineffective cardiac risk factor management and progressive atherosclerosis is discussed.
    背景与目标: : 该手稿描述了一名患有多种心脏危险因素的中年患者的冠状动脉循环的顺序血管造影,内皮和血管反应性特征,这些患者在6年内发生了血流动力学显着的冠状动脉粥样硬化。一名56岁的女性表现出冠状动脉粥样硬化的明显血管造影进展,随着时间的推移,在严重的内皮功能障碍的情况下开始出现轻微的管腔不规则。讨论了内皮功能障碍,无效的心脏危险因素管理与进展性动脉粥样硬化的关系。
  • 【衰老和动脉粥样硬化: 改变心血管疾病预防的考虑因素,因为永生的障碍是在老年。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Hazzard WR,Ettinger WH Jr
    BACKGROUND & AIMS: :Of all the risk factors to cardiovascular disease (CVD), age is the most powerful: CVD incidence and prevalence rise progressively at all ages beyond young adulthood. This reflects the central role of time, and hence duration, in the atherogenic process. It also reflects age-related changes in physiology - notably alterations in body mass and composition favoring increased adiposity and in sex hormone secretion (combining adverse effects of androgens on lipoprotein lipid levels in males, lowering HDL, and of the decline in estrogens in postmenopausal females, raising LDL). The interactions among the passage of time, these physiological changes and perhaps aging per se, and pathological forces such as cigarette smoking, hypertension, and genetically determined dyslipoproteinemia conspire to accelerate the rate of atherogenesis. Thus clinical atherosclerosis and its complications rise exponentially with increasing age in the population at large. However, the relationship between dyslipoproteinemia and CVD risk in the individual patient actually declines with advancing age. This apparent paradox reflects confounding introduced by the advent of disease processes that cause wasting and inflammation such as cancer, infection, diabetes, trauma, and even CVD that actually lower lipid levels, frequently to the level of hypocholesterolemia. Thus, while with age the population-attributable risk of hypercholesterolemia (and/or low HDL) rises, the cholesterol-attributable risk in the individual falls. As a result the prescription of lipid-lowering therapy in elderly patients requires exquisite individualization: patients most likely to benefit are those with existing CVD (i.e., in secondary prevention) who nevertheless enjoy robust health and are highly motivated to comply with demanding regimens of diet and exercise plus drugs where needed to reach target LDL levels (less than 100 mg/dl). At the other extreme are those least likely to benefit: patients who are frail and failing from CVD or other wasting diseases of old age that present a more immediate threat to survival.
    背景与目标: : 在心血管疾病 (CVD) 的所有危险因素中,年龄是最强大的: CVD的发病率和患病率在成年后的所有年龄段都逐渐上升。这反映了时间以及持续时间在动脉粥样硬化过程中的核心作用。它还反映了与年龄相关的生理变化-特别是体重和组成的变化,有利于肥胖和性激素分泌增加 (结合雄激素对男性脂蛋白脂质水平的不利影响,降低HDL和雌激素的下降) 绝经后女性,提高LDL)。时间的流逝,这些生理变化以及可能的衰老本身以及诸如吸烟,高血压和遗传决定的血脂异常等病理力量之间的相互作用共同加速了动脉粥样硬化的发生速度。因此,随着人口年龄的增长,临床动脉粥样硬化及其并发症呈指数增长。然而,个体患者的血脂蛋白血症与CVD风险之间的关系实际上随着年龄的增长而下降。这种明显的悖论反映了由引起消瘦和炎症的疾病过程的出现所引起的混淆,例如癌症,感染,糖尿病,创伤甚至CVD,这些疾病实际上降低了脂质水平,通常降低到了低胆固醇血症的水平。因此,随着年龄的增长,高胆固醇血症 (和/或低HDL) 的人群归因风险上升,个体的胆固醇归因风险下降。因此,老年患者的降脂治疗处方需要精巧的个体化: 最有可能受益的患者是患有CVD的患者 (即,在二级预防中),尽管如此,他们仍然享有健康,并且在需要达到目标LDL水平 (低于100 mg/dl) 的情况下高度积极地遵守饮食和运动加药物的要求。另一个极端是那些最不可能受益的人: 虚弱且因CVD或其他老年消耗性疾病而失败的患者,这些患者对生存构成了更直接的威胁。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录