动脉粥样硬化血管壁的Warburg效应

动脉粥样硬化(As)是一种以动脉血管壁脂质沉积为病理特征的慢性炎症性疾病。致As因素所诱导的血管壁慢性炎症在该疾病的病理进程中起着重要作用。单核细胞/巨噬细胞的能量代谢重新编程与As的发生发展密切相关。Warburg效应是细胞能量代谢的重要方式,该效应可能参与As的某些病理过程,如血管平滑肌增殖、内皮细胞功能障碍和炎症等。本文就As血管壁的Warburg效应进行综述。     

高密度脂蛋白抗动脉粥样硬化功能的丢失与恢复

巨噬细胞在动脉粥样硬化(As)起始、发展的全过程扮演着中心角色,从巨噬细胞脂质积聚和炎症反应入手,寻求某个作用环节进行干预有可能成为非常合适的As治疗靶点。内皮功能失调是As发生的一个重要起始事件,内皮细胞释放的粘附分子如ICAM、VCAM、ELAM及Selectin,介导单核细胞活化并向内膜下募集、分化,巨噬细胞释放的单核细胞趋化蛋白1(MCP-1)及巨噬细胞移动抑制因子(MIF)在单核细胞的移行和分化中发挥重要作用。MIF还可诱导ICAM、....     

巨噬细胞移动抑制因子在动脉粥样硬化中的作用研究进展

动脉粥样硬化是动脉血管壁对损伤和刺激的慢性炎症和免疫反应，其发病机理尚未完全清楚。系列细胞因子对动脉粥样硬化的形成和发展等方面具有不同程度的作用，特别是巨噬细胞移动抑制因子和肿瘤坏死因子α在单核细胞聚集、粘附、迁移和巨噬细胞吞噬脂质等形成动脉粥样硬化过程中起着重要的作用。本文主要就巨噬细胞移动抑制因子在动脉粥样硬化进展中的变化和作用作一综述。     

炎性细胞在动脉粥样硬化中作用的研究进展

心血管疾病(CVD)严重威胁人类的健康,动脉粥样硬化(As)作为CVD的重要病理基础,是氧化脂质在血管壁沉积引起的一种慢性免疫炎性病变。各种免疫炎性细胞在As的发生发展中起关键作用,因此不断探索免疫细胞在病变中的作用机制,对研究CVD的治疗策略是至关重要的。本文主要对中性粒细胞、单核细胞、淋巴细胞、树突状细胞、肥大细胞在As中的作用进行综述。     

动脉粥样硬化中单核细胞招募与泡沫细胞形成

动脉粥样硬化是一种慢性炎症疾病,单核细胞和激活的内皮细胞间的相互作用在动脉粥样硬化病变进程中起着关键性的作用.在动脉粥样硬化的早期阶段,单核细胞在黏附分子和细胞因子的作用下进入内膜并分化为巨噬细胞.在受体和胞饮介导下,分化而来的巨噬细胞对内膜下的脂质进行摄取,脂质负荷的巨噬细胞转化为泡沫细胞,大量泡沫细胞的蓄积将形成动脉粥样硬化的脂质核心.     

白三烯与动脉粥样硬化

动脉粥样硬化是一种多因素疾病,目前认为是高胆固醇血症并发血管壁炎症的结果。动脉粥样硬化形成最有可能的事件序列是血管功能异常或损伤,单核细胞募集和巨噬细胞形成,脂质沉积和细胞外基质合成。内皮细胞,平滑肌细胞,浸润的单核细胞和T淋巴细胞之间复杂的相互作用决定了脂质浸润到损伤血管的过程。最近的研究显示白三烯(leukotrienes,LTs)可以影响到所有这些细胞参与这个过程的活动。白三烯拮抗剂也被用于特定的动物模型来研究它们在动脉粥样硬化形成中的作用。这些研究提示了白三烯及其拮抗剂在动脉粥样硬化形成过程中以前未被认识的作…     

心痛定抗动脉粥样硬化形成作用机制的探讨

本文观察了慢通道阻滞剂心痛定对食饵性高酯血症家兔动脉粥样硬化(AS)斑块形成的形响,测定了在高脂状态下血小板内钙调节的改变对血小板聚集与释放反应的影响,旨在进一步探讨高脂血症时血小板机能亢进的发生机制,以及慢通道阻滞剂心痛定抗动脉粥样硬化形成的作用机制。实验结果证明,心痛定具有明显的抗食饵性高脂血症家兔AS形成的作用,并有明显的降血脂,减少动脉胆固醇蓄积和抑制高脂状态下血小板机能亢进的作用,故是一种有希望的抗As形成药物。     

炎性信号通路在动脉粥样硬化中的机制与中医药干预作用研究进展

动脉粥样硬化（As）是冠心病、脑卒中等疾病的重要病理基础，除脂质代谢紊乱、血管内皮损伤、氧化应激反应等危险因素外，炎性信号通路介导的炎症反应作为新的危险因素贯穿于As的形成发展过程中已得到广大研究者的认可。中医药因其作用广，毒副作用小，被广泛应用于防治As中。本文就炎性信号通路在As中的作用机制，以及中医药通过干预炎性信号通路在抗As机制方面的研究进展作一综述。     

普伐他丁、维生素E、开搏通对家兔高脂血症、动脉粥样硬化和脂肪肝形成的影响

为寻找能兼顾防治高脂血症、动脉粥样硬化和脂肪肝的有效药物，观察普伐他丁、维生素E、开搏通对家免高脂血症、动脉粥样硬化和脂肪肝形成的影响。结果发现，普伐他丁可显著降低血脂和改善动脉粥样硬化病变，并有一定抗脂肪肝作用，联用维生素E可减轻其潜在肝毒性；开搏通有一定的抗动脉粥样硬化作用，且不影响血脂和肝脂质代谢。提示普伐他丁(最好联用维生素E)、开搏通可安全用于高脂血症、动脉粥样硬化和脂肪肝患者的治疗。     

糖基化低密度脂蛋白增加血管内皮对单核细胞的粘附作用

血管内皮细胞对单核细胞的粘附作用增加是动脉粥样硬化（ＡＳ）的重要病理过程之一，糖尿病患者高水平的糖基化低密度脂蛋白（ＧＬＤＬ）可通过改变脂质代谢途径，促进泡沫细胞形成和增强血小板聚集功能等促进或加速动脉粥样硬化的发生。但是，ＧＬＤＬ是否通过对内皮细胞...     

Lipoprotein (a) up-regulates the expression of the plasminogen activator inhibitor 2 in human blood monocytes

Elevated plasma lipoprotein (a) (Lp[a]) and cardiac events show a modest but significant association in various clinical studies. However, the influence of high Lp(a) on the gene expression in blood monocytes as a major cell involved in atherogenesis is poorly described. To identify genes influenced by elevated serum Lp(a), the gene expression was analyzed on a complementary DNA microarray comparing monocytes from a patient with isolated Lp(a) hyperlipidemia and coronary heart disease with monocytes from a healthy blood donor with low Lp(a). By using this approach, numerous genes were found differentially expressed in patient-versus-control monocytes. Verification of these candidates by Northern blot analysis or semiquantitative polymerase chain reaction in monocytes from additional patients with Lp(a) hyperlipidemia and healthy blood donors with elevated Lp(a) confirmed a significant induction of plasminogen activator inhibitor type 2 (PAI-2) messenger RNA (mRNA) in monocytes from male, but not from female, individuals with high Lp(a), indicating that this observation is gender specific. This led also to increased intracellular and secreted PAI-2 protein in monocytes from male probands with Lp(a) hyperlipidemia. Plasminogen activator inhibitor type 1 (PAI-1) mRNA was found suppressed only in the patients' monocytes and not in healthy probands with high Lp(a) levels. Purified Lp(a) induced PAI-2 mRNA and protein and reduced PAI-1 expression in monocytes isolated from various controls. The finding that PAI-2 is elevated in monocytes from male patients with isolated Lp(a) hyperlipidemia and male healthy probands with high Lp(a) and that purified Lp(a) up-regulates PAI-2 in control monocytes in vitro indicate a direct, but gender-specific, effect of Lp(a) for the induction of PAI-2 expression.     

阿托伐他汀对高脂血症患者补体调节蛋白CD55、CD59表达的影响

目的观察高脂血症患者补体调节蛋白CD55、CD59的表达及其与补体活化、脂代谢紊乱之间的关系,并探讨阿托伐他汀对其的影响。方法高脂血症患者67例,年龄、性别、体重与其匹配的健康对照24例,使用流式细胞仪测定外周血白细胞CD55、CD59的表达,分析CD55、CD59表达水平与血脂、补体活化指标、炎症因子及相关临床指标间的关系,对其中24例高脂血症患者使用阿托伐他汀治疗8~12周,观察治疗前后CD55、CD59表达的变化。结果高脂血症患者CD55阳性淋巴细胞、单核细胞平均荧光强度(MFI)低于健康对照组(2.07±0.28比2.29±0.44及3.45±1.02比4.33±2.32,P<0.01及P<0.05),CD55阳性淋巴细胞MFI与腰围、腰臀比值、高敏C反应蛋白、补体C5a呈负相关,与血脂不相关;补体C5a水平与CD55阳性淋巴细胞、单核细胞、粒细胞MFI负相关,与TG和舒张压正相关,与CD59表达指标不相关;阿托伐他汀治疗后CD59阳性淋巴细胞、单核细胞、粒细胞MFI增加(4.34±1.16比3.69±0.76,4.52±1.36比3.91±0.89,5.67±1.72比4.56±1.03,P<0.05,P<0.05及P<0.01),与血脂变化不相关。结论高脂血症患者补体调节蛋白CD55表达下调,可能与肥胖、腹型脂肪分布、炎症状态有关,不受血脂的直接影响;CD55表达水平与补体活化有关;阿托伐他汀干预可使CD59表达上调,与调脂作用无关。     

Binding of monocytes from normolipidemic hyperglycemic patients with type 1 diabetes to endothelial cells is increased in vitro.

Increased endothelial binding and emigration of monocytes play a dominant role in the pathogenesis of atherosclerosis in diabetes mellitus. Previous studies revealed that hyperlipidemia correlates with monocyte binding in vitro. The aim of this study was to characterize the monocyte-endothelial interaction of leucocytes of hyperglycemic patients with type 1 diabetes but lacking hyperlipidemia. We isolated monocytes from healthy controls and normolipidemic type 1 diabetes patients with elevated levels of HbA1c and quantified monocyte binding by an immunoilluminometric cell adhesion assay. Purity of isolated monocytes was at least 98%. Endothelial binding of monocytes from patients with type 1 diabetes was found to be significantly increased compared to controls (19.2 +/- 3.9% vs. 14.9 +/- 3.5%). This difference of monocyte binding remained unchanged if the endothelial cells were stimulated with 27.7 mmol/l glucose for seven days prior to adhesion studies (31.5 +/- 4.9% in diabetes patients vs. 25.8 +/- 4.1% in controls) whereby monocyte binding markedly increased under these hyperglycemic conditions. Furthermore, an increased CD11b expression could be demonstrated on monocytes of normolipidemic hyperglycemic type 1 diabetes patients. Thus, we suggest that hyperglycemia per se may contribute to increased monocyte binding to endothelial cells by promoting leucocyte integrin expression. Recently performed studies of our group strengthen the hypothesis that this monocyte activation is mediated by stimulation of the beta-isoform of proteinkinase C.     

Adverse effects of the treatment for hyperlipidemia

A variety of treatments to lower elevated plasma lipid levels in patients with hyperlipidemia are available. Adverse side effects ranging from mere annoyances to uncommon serious consequences may be associated with dietary modification, recreational physical exercise, and drug intervention. As in other clinical circumstances, risk-to-benefit ratios must be taken into consideration in the management of hyperlipidemia.     

Immunosuppression and metabolic syndrome in renal transplant recipients

Cardiovascular disease is the major cause of death in renal transplant recipients. Renal transplant recipients share the same cardiovascular risk factors as the general population, including hypertension, hyperlipidemia, diabetes mellitus, smoking, and positive family history. However, renal transplant recipients are also exposed to transplant-specific risk factors such as chronic immunosuppression. Most renal transplant recipients receive combinations or permutations of immunosuppressive drugs including a calcineurin inhibitor (cyclosporine or tacrolimus), a mammalian target of rapamycin (mTOR) inhibitor (sirolimus), an antiproliferative drug (mycophenolate mofetil and azathioprine), and corticosteroids. Cyclosporine and tacrolimus can induce glucose intolerance, hypertension, and hyperlipidemia. Sirolimus can induce hyperlipidemia. Corticosteroids can induce glucose intolerance, hypertension, hyperlipidemia, and weight gain. Central to the development of metabolic complications in renal transplant recipients is insulin resistance induced by immunosuppressive drugs. Insulin resistance is considered to be the central pathophysiological feature of metabolic syndrome, which is linked to increased risk of cardiovascular disease and to chronic renal failure. Therefore, metabolic syndrome likely contributes to cardiovascular disease and chronic renal allograft dysfunction in renal transplant recipients. Treatment of metabolic complications in renal transplant recipients is difficult, as conversion to an alternate immunosuppressive drug may lead to introduction of new metabolic complications, and as discontinuation of immunosuppressive therapy may lead to rejection. Future research should focus on designing immunosuppressive regimens that have minimal effects on insulin resistance and metabolic complications but that are effective in preventing acute rejection and in prolonging both allograft and patient survival.     

Specific detection of monocytic lysozyme within normal and leukemic cells.

A murine monoclonal antibody against human lysozyme (AHL MoAb) was produced and tested on normal and leukemic monocytes using flow cytometry. The antibody gave a positive reactivity on normal monocytes permeabilized by saponin (82% to 98% of positive cells) and a negative reactivity on normal permeabilized neutrophils. This monocyte-specific reactivity had not been observed using a polyclonal antibody. Nevertheless, immunoblotting detected lysozyme in both monocyte and polymorphonuclear leukocyte (PMNL) lysates. The AHL MoAb, in the presence of lysozyme substrate (Micrococcus lysodeikticus cell walls), strongly inhibited the enzymatic activity. Flow cytometric analysis of leukemic cells isolated from patients suffering from different subtypes of acute myeloid leukemia (French-American-British [FAB] classification FAB M1-5) showed a highly significant positivity of FAB M5 for lysozyme compared with the other subtypes. The present results were consistent with the detection of a lysozyme epitope by AHL MoAb located near the catalytic site in monocytes. The same epitope was probably masked in PMNL granules.     

Morphological evaluation of monocytes and their precursors

The monocyte is still the most difficult cell to identify with confidence in the peripheral blood or in the bone marrow in healthy individuals as well as in patients with infections, and in those with leukemic proliferations. The goal of this study was to establish morphological definitions so that monocytes, including immature monocytes, could be separated from the spectrum of monocyte precursors. Cells from peripheral blood or bone marrow were selected to provide a large panel of normal and leukemic cells at different maturational stages and were submitted to 5 experts, who had previously reached a consensus, on the basis of microscopy, in defining 4 subtypes: monoblast, promonocyte, immature monocyte, mature, monocyte. They achieved a good concordance rate of 76.6% and a high κ rate confirming that the criteria for defining the 4 subtypes could be applied consistently. It has now to be established whether these monocyte subtypes correlate with immunological or molecular markers and are clinically relevant.     

Receptor for platelet-activating factor (PAF) is not detectable by flow cytometry on the surface of myeloid leukemic cells

Flow cytometry was applied to test for platelet-activating-factor receptor (PAF-R) presence on the membranes of acute myeloid leukemia (AML) cells. We have used six human AML cell lines and freshly taken density gradient separated blasts from the bone marrow of ten AML patients covering the majority of French–American–British (FAB) subtypes. Additionally, we have used one histiocytic lymphoma cell line and mature human granulocytes/monocytes as controls. Our results indicate lack of membrane PAF-R on AML of all FAB subtypes tested. This was particularly true for the more mature and differentiated subtypes M₄ and M₅, including monocytic cell elements, and the promyelocytic M₃ AML. In contrast, membrane PAF-R could be easily detected in a histiocytic lymphoma cell line and mature granulocytes/monocytes from peripheral blood used as positive controls. In conclusion, this observation precludes the use of membrane PAF-R as an immunophenotypic marker for AML classification or detection of minimal residual disease.     

缺血性卒中患者的牛津郡社区卒中项目分型与危险因素的关系

目的探讨缺血性卒中患者牛津郡社区卒中项目（OCSP）的分型及各亚型与卒中危险因素的关系。方法前瞻性连续登记发病到入院〈2周的缺血性卒中患者932例。根据OCSP分型标准,将其分为完全前循环梗死（TACI）、部分前循环梗死（PACI）、腔隙性梗死（LACI）及后循环梗死（POCI）4组。记录患者的性别、年龄、民族以及高血压、糖尿病、高脂血症、吸烟、饮酒史情况。分析不同危险因素对各卒中亚型发生风险的影响。结果@932例中,LACI组为463例（49．7％）、PACI组为326例（35．0％）、POCI组为78例（8．4％）、TACI组为65例（7．0％）。②年龄、高血压、糖尿病、高脂血症、脑出血、吸烟史在各亚型组间的差异无统计学意义。POCI组中,男性比例最高（75．6％）;TACI组中,回族（21．5％）、缺血性卒中（36．9％）、心房颤动（20．0％）及短暂性脑缺血发作（TIA）患者（21．5％）的比例最高（21．5％）;LACI组中,饮酒者比例最高（50．3％）。③糖尿病、高血压、高脂血症、吸烟、饮酒、缺血性卒中、TIA、脑出血、心房颤动史对POCI发生的相对危险性差异均无统计学意义;糖尿病、高血压、高脂血症、吸烟史对各型卒中发生的相对危险性差异也均无统计学意义。饮酒史和TIA史增加了LACI的风险（OR=1．488,95％CI：1．148～1．928;OR=1．686,95％C1：1．155—2．462）;缺血性卒中史增加了PACI和TACI的风险（OR=1．466,95％CI：1．058～2．032;OR=2．472,95％CI：1．453—4．205）;脑出血史和心房颤动增加了TACI（OR=2．570,95％CI：1．036—6．379）;OR：4．266,95％CI：2．174—8．368）的风险。结论OCSP各亚型中,LACI亚型的发生率最高;不同的危险因素可能增加OCSP不同亚型的发生风险。     

Functions of cyclophilin A in atherosclerosis

Cyclophilin A (CypA) is a ubiquitously distributed protein present both in intracellular and extracellular spaces. In atherosclerosis, various cells, including endothelial cells, monocytes, vascular smooth muscle cells and platelets, secrete CypA in response to excessive levels of reactive oxygen species. Atherosclerosis, a complicated disease, is the result of the interplay of different risk factors. Researchers have found that CypA links many risk factors, including hyperlipidemia, hypertension and diabetes, to atherosclerosis that develop into a vicious cycle. Furthermore, most studies have shown that secreted CypA participates in the developmental process of atherosclerosis via many important intracellular mechanisms. CypA can cause injury to and apoptosis of endothelial cells, leading to dysfunction of the endothelium. CypA may also induce the activation and migration of leukocytes, producing proinflammatory cytokines that promote inflammation in blood vessels. In addition, CypA can promote the proliferation of monocytes/macrophages and vascular smooth muscle cells, leading to the formation of foam cells and the remodelling of the vascular wall. Studies investigating the roles of CypA in atherosclerosis may provide new direction for preventive and interventional treatment strategies in atherosclerosis.