非对称性二甲基精氨酸水平与缺血性脑卒中的相关性

目的 探讨非对称性二甲基精氨酸(asymmetricaldimethylarginine,ADMA)对缺血性脑卒中诊断及病情判断的临床价值.方法 选取88例缺血性脑卒中患者,采用欧洲卒中量表(ESS)进行神经功能缺损评分分为轻度卒中组(31例)、中度卒中组(39例)和重度卒中组(18例).另选30名年龄、性别构成比与患者组差异无统计学意义的健康志愿者为对照组,分别用高效液相色谱联合质谱法测定血浆中ADMA的水平,分析血浆ADMA水平在对照组和缺血性脑卒中各亚组之间的相关性.结果 对照组、轻度卒中组、中度卒中组和重度卒中组的血浆ADMA水平(±s,μmol/L)分别为:1.0±0.10,2.90±0.30,4.82±0.21及6.61±0.23.与对照组血浆ADMA水平比较,患者组各亚组ADMA水平明显升高,其差异有统计学意义(P<0.05);轻度卒中组与中度和重度卒中组的差异有统计学意义(P<0.05);重度组与中度卒中组的差异有统计学意义(P<0.05),与轻度卒中组的差异有统计学显著性意义(P<0.001).结论 血浆ADMA水平与缺血性脑卒中的发病及病变严重程度相关,检测血浆ADMA水平的变化,对缺血性脑卒中的诊断和病情判断、指导治疗有一定的帮助.     

高糖诱导人脐静脉内皮细胞衰老过程中活性氧与二甲基精氨酸二甲胺水解酶-非对称性二甲基精氨酸系统的变化

目的 观察高糖加速内皮细胞衰老过程中细胞内活性氧(ROS)水平与二甲基精氨酸二甲胺水解酶-非对称性二甲基精氨酸(DDAH-ADMA)系统的变化.方法 正常糖浓度培养液(5.5 mmol/L)和高糖培养液(11.0、22.0、33.0 mmol/L)作用于人脐静脉内皮细胞48 h后,用β-半乳糖苷酶染色鉴定衰老细胞,聚合酶链反应-酶联免疫吸附法(PCR-ELISA)检测端粒酶活性,流式细胞仪检测细胞内ROS水平,液质联用仪检测细胞上清液中ADMA含量及DDAH活性.结果 与正常糖浓度组相比,11.0、22.0、33.0 mmol/L高糖浓度组β-半乳糖苷酶染色阳性细胞率明显增高[(7.00±1.73)%、(12.67±2.03)%、(16.00±2.26)%比(4.00±1.33)%,P＞0.05、P＜0.05、P＜0.05],端粒酶活性显著下降[(91.32±4.01)%、(78.44±3.78)%、(56.04±3.35)%比100%,均P＜0.05];随细胞衰老程度加重,细胞内ROS水平(mfi)显著升高(159.84±27.52、188.99±18.77、244.56±20.96比117.11±18.76,P＜0.05或P＜0.01),ADMA水平(μmol/L)显著升高(0.78±0.14、0.88±0.18、1.08±0.15比0.70±0.12,P＞0.05、P＜0.05、P＜0.05),DDAH活性显著下降[(91.32±4.01)%、(78.44±3.78)%、(56.04±3.35)%比100%,均P＜0.05].结论 高糖可加速内皮细胞衰老进程,其机制可能与氧化应激水平增强、抑制DDAH活性使ADMA含量增加有关.

Abstract：

Objective To investigate the changes in reactive oxygen species (ROS) and dimethylarginine dimethylaminohydrolase-asymmetric dimethylarginine (DDAH-ADMA) system in the process of endothelial cell senescence after exposure to high glucose. Methods The human umbilical vein endothelial cells (HUVECs) were cultured with different concentrations of glucose, e.g. 5. 5 mmol/L (normal level),and high levels as 11. 0, 22. 0 and 33. 0 mmol/L. for 48 hours, respectively. Subsequently, SA-β-gal staining was used to evaluate senescence of cells. Telomerase activity was detected by polymerase chain reactionenzyme linked immunosorbent assay (PCR-ELISA). The intracellular ROS level was measured by flow cytometry. The ADMA concentration and DDAH activity were determined with high-performance liquid chromatography. Results Compared with normal glucose concentration group, after the endothelial cells were treated with high glucose concentration (11. 0 - 33. 0 mmol/L) for 48 hours, the number of SA-β-gal positive cells was increased significantly [(7.00±1. 73)%, (12. 67±2. 03)%, (16. 00±2. 26)% vs. (4. 00±1.33)%, P＞0.05, P＜0.05, P＜0.05] and the telomerase activity was inhibited dramatically [(91. 32±4.01)%, (78. 44±3. 78)%, (56. 04±3. 35)% vs. 100%, all P＜0. 05]. The ROS level (mfi) was increased in all high glucose groups (159. 84±27. 52, 188. 99±18. 77, 244. 56±20. 96 vs. 117.11±18. 76, P＜0. 05 or P＜0. 01). At the same time, the ADMA (μmol/L) production was increased (0. 78±0. 14, 0. 88±0.18,1. 08±0.15 vs. 0. 70±0. 12, P＞0. 05, P＜0. 05, P＜0. 05), and DDAH activity was decreased [(91. 32±4.01)%, (78.44±3.78)%, (56. 04± 3. 35)% vs. 100%, all P＜0.05]. Conclusion High glucose can accelerate endothelial cells senescence in dose-dependent manner and the underlying mechanism may be related to an increased oxidative stress and change in DDAH-ADMA system.     

高糖诱导人脐静脉内皮细胞衰老过程中活性氧与二甲基精氨酸二甲胺水解酶-非对称性二甲基精氨酸系统的变化

Objective To investigate the changes in reactive oxygen species (ROS) and dimethylarginine dimethylaminohydrolase-asymmetric dimethylarginine (DDAH-ADMA) system in the process of endothelial cell senescence after exposure to high glucose. Methods The human umbilical vein endothelial cells (HUVECs) were cultured with different concentrations of glucose, e.g. 5. 5 mmol/L (normal level),and high levels as 11. 0, 22. 0 and 33. 0 mmol/L. for 48 hours, respectively. Subsequently, SA-β-gal staining was used to evaluate senescence of cells. Telomerase activity was detected by polymerase chain reactionenzyme linked immunosorbent assay (PCR-ELISA). The intracellular ROS level was measured by flow cytometry. The ADMA concentration and DDAH activity were determined with high-performance liquid chromatography. Results Compared with normal glucose concentration group, after the endothelial cells were treated with high glucose concentration (11. 0 - 33. 0 mmol/L) for 48 hours, the number of SA-β-gal positive cells was increased significantly [(7.00±1. 73)%, (12. 67±2. 03)%, (16. 00±2. 26)% vs. (4. 00±1.33)%, P＞0.05, P＜0.05, P＜0.05] and the telomerase activity was inhibited dramatically [(91. 32±4.01)%, (78. 44±3. 78)%, (56. 04±3. 35)% vs. 100%, all P＜0. 05]. The ROS level (mfi) was increased in all high glucose groups (159. 84±27. 52, 188. 99±18. 77, 244. 56±20. 96 vs. 117.11±18. 76, P＜0. 05 or P＜0. 01). At the same time, the ADMA (μmol/L) production was increased (0. 78±0. 14, 0. 88±0.18,1. 08±0.15 vs. 0. 70±0. 12, P＞0. 05, P＜0. 05, P＜0. 05), and DDAH activity was decreased [(91. 32±4.01)%, (78.44±3.78)%, (56. 04± 3. 35)% vs. 100%, all P＜0.05]. Conclusion High glucose can accelerate endothelial cells senescence in dose-dependent manner and the underlying mechanism may be related to an increased oxidative stress and change in DDAH-ADMA system.     

非对称性二甲基精氨酸与冠心病的相关性研究进展

<正>非对称性二甲基精氨酸(ADMA)是精氨酸甲基化的衍生物,广泛分布于人体的组织细胞及体液中。ADMA是内源性一氧化氮合酶(e NOS)主要的抑制剂,而e NOS为合成一氧化氮(NO)所必需[1]。研究表明,血浆ADMA浓度升高会使NO的合成受抑,导致血管内皮功能障碍和动脉粥样硬化。1非对称性二甲基精氨酸的生成与代谢ADMA是含甲基化精氨酸残基的蛋白质,由特     

辛伐他汀对非对称性二甲基精氨酸引起的内皮细胞炎症反应的抑制作用

目的:观察辛伐他汀对非对称性二甲基精氨酸(ADMA)引起的人脐静脉内皮细胞(HUVECs)炎症反应的抑制作用,探讨他汀类药物除降脂作用以外的其他抗动脉粥样硬化机制.方法:体外培养的人济静脉内皮细胞,待细胞生长到融合状态时加入不同浓度的ADMA(3、10、30μmol/L)作用48h,观察ADMA对内皮细胞炎症因子产生的影响.不同浓度的辛伐他汀预先孵育20min,然后加入ADMA(30 μmol/L)作用48h,用ELISA法检测上清液中MCP-1、IL-6和TNF-a浓度,比色法检测一氧化氮(NO)含量的变化.结果:ADMA呈剂量依赖性增加上清液中MCP-1、IL-6和TNF-α浓度并降低NO的含量.外源性补充辛伐他汀可逆转ADMA的效应,且呈剂量依赖性(P＜0.05).用一氧化氮合酶抑制剂左旋硝基精氨酸甲酯(L-NAME)抑制一氧化氮合酶降低NO的合成后,可部分取消辛伐他汀的保护作用.结论:ADMA通过诱导炎症反应,引起内皮功能紊乱,其紊乱程度与ADMA的浓度有关;而辛伐他汀能以剂量依赖的方式抑制ADMA诱导的炎症反应,其机制除与其增加NO的合成有关外,可能还有其他物质或途径的参与.     

非对称性二甲基精氨酸与血液透析中血压变化的研究

目的研究血液透析(Hemodialysis,HD)患者血浆非对称性二甲基精氨酸(Asymmetric dimethylarginine,ADMA)与透析中血压变化的关系。方法经生物电阻抗检测干体质量达标且符合入选标准的维持性血液透析(Maintenance Hemodialysis,MHD)患者31名进入研究,根据血液透析过程中血压波动情况分为年龄相匹配的3组:透析中高血压组(n=11)、低血压组(n=12)和血压平稳组(n=8)。用酶联免疫吸附(Enzyme linked immunosorbent assay,ELISA)法检测患者透析前、后血浆ADMA水平,探讨ADMA与透析中血压变化的关系,并进行组间矿物质骨代谢指标、电解质、营养指标、炎性标记物、血脂水平、脉压差和降压治疗等的比较。结果 31例MHD患者透析前血ADMA均值为3.37±1.48μmol/L,透析后降至1.71±0.80μmol/L(P0.001),均显著高于国外正常参考值。透析中低血压组透析前、后血ADMA值(4.38±1.56μmol/L,2.25±0.83μmol/L)均高于透析中高血压组和血压平稳组,差异有统计学意义(2.70±1.18μmol/L,1.32±0.60μmol/L和2.78±0.88μmol/L,1.43±0.56μmol/L;P=0.006和0.006)。透析中高血压组患者透析中的平均脉压差高于透析中低血压组和血压平稳组(62.41±11.57mmHg,48.80±12.88 mmHg和44.56±8.30 mmHg,P=0.004)。高血压组碱性磷酸酶(ALP)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)和高敏C-反应蛋白(high-sensitivity c-reactive protein,Hs-CRP)均高于血压平稳组(P值分别为0.036、0.039、0.046、0.046),低血压组同样指标也高于血压平稳组(P值分别为0.046、0.035、0.040、0.004),上述指标在高血压组和低血压组间差异无统计学意义(P0.05)。结论在干体质量达标的MHD患者中,血ADMA水平显著高于正常,透析过程中的血压波动与内皮功能不良、血管僵硬、微炎症状态等密切相关。     

血浆非对称性二甲基精氨酸水平与2型糖尿病视网膜病变的关系

非对称性二甲基精氨酸(asymmetric dimethylarginine,ADMA)是一个内源性一氧化氮合成酶(nitric oxide synthesis,NOS)抑制剂,它可通过抑制一氧化氮(NO)的产生,影响血管内皮功能[1].     

非对称性二甲基精氨酸和肿瘤坏死因子对原发性高血压左心室构型的影响

目的 观测正常人及高血压患者在不同左心室构型组血清中的肿瘤坏死因子α(TNF-α)和非对称性二甲基精氨酸(ADMA)浓度变化,并探讨TNF-α和ADMA在高血压心脏损害中的病理生理作用.方法 选取体检健康人员30名为正常对照组.轻中度高血压患者66例,根据左心室质量指数(LVMI)和相对室壁厚度(RWT)将其分为4组,即正常左心室构型组:LVMI和RWT均正常;向心性构型组:LVMI正常,RWT增大;向心性肥厚型组:LVMI和RWT均增大;离心性肥厚型组:LVMI增大,RWT正常.采用放射免疫法及反相高效液相色谱法分别测定各组血清中TNF-α及ADMA.结果 对照组和以上4组中TNF-α分别为(11.86±2.45)、(22.08±4.67)、(25.88.4±5.36)、(32.54±5.63)、(48.72±8.86)ng/L;ADMA:(0.78±0.22)、(1.32±0.18)、(1.87±0.20)、(3.03±0.14)、(4.11±0.17)p.mol/L.血清TNF-α和ADMA水平随左心室构型严重程度的增加而升高,左心室构型组患者均明显高于正常对照组(P均<0.01),且左心室重构各亚组间两两比较差异均有统计学意义(P均<0.01).结论 TNF-α和ADMA可能参与了高血压左心室构型的发生和发展.     

新的血管内皮损伤标记物——非对称性二甲基精氨酸

一氧化氮(nitric oxide,NO)是强有力的内源性血管舒张因子,它能抑制血管疾病的关键步骤,如白细胞黏附、血小板聚集和血管平滑肌细胞增生等,在维持内皮功能的稳定上起到重要作用。一氧化氮合成酶(nitric oxide synthase,NOS)催化精氨酸转化为瓜氨酸和NO,而NO具有舒张血管作用。如今众多实验表明,     

非对称性二甲基精氨酸与2型糖尿病及其大血管并发症关系的研究

目的 研究血清非对称性二甲基精氨酸(ADMA)与2型糖尿病及其大血管并发症的关系,观察强化治疗对ADMA水平的影响.方法 2型糖尿病患者97例(DM组),包括无大血管并发症亚组(DM1亚组)22例和伴大血管并发症亚组(DM2亚组)75例.所有患者均入院接受降糖和(或)降压、调脂等强化治疗2周,并于2个月后对患者进行随访.选取40例健康体检者作为正常对照组(NC组).用酶联免疫法(ELISA)检测血清ADMA水平及生化仪器检测其他相关指标.用SPSS 12.0软件包进行分析.结果 2型糖尿病两个亚组血清ADMA水平均明显高于正常对照组(P<0.05),且2型糖尿病伴大血管并发症亚组平均血清ADMA水平高于2型糖尿病无大血管并发症亚组(P<0.05).多元线性回归分析显示,在2型糖尿病组(DM组)中糖化血红蛋白(HbA1c)、总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)均与ADMA水平呈正相关.经强化治疗后其血清ADMA水平明显下降(P<0.05).结论 血清ADMA水平与2型糖尿病及其大血管并发症密切相关,与HbA1c、TC和LDL-C均呈正相关.强化治疗可以使2型糖尿病患者血清ADMA水平明显下降.     

Association of asymmetric dimethylarginine and endothelial dysfunction.

There is abundant evidence that the endothelium plays a crucial role in the maintenance of vascular tone and structure. One of the major endothelium-derived vasoactive mediators is nitric oxide (NO), which has been characterized as an "endogenous anti-atherosclerotic molecule". Synthesis of NO can be selectively inhibited by guanidino-substituted analogs of L-arginine, which act as competitive inhibitors at the active site of the enzyme. One such analog is asymmetric dimethylarginine (ADMA), a compound that has been found in human plasma and urine and exerts the activity of an endogenous inhibitor of NO synthase. In contrast to ADMA, its regioisomer symmetric dimethylarginine (SDMA) does not inhibit NO synthase. The methyl groups contained within the dimethylarginine molecules are derived from S-adenosylmethionine, an intermediate in the homocysteine/methionine pathway. There is experimental evidence that homocysteine may affect endothelium-dependent vascular function by increasing the formation of ADMA. Both ADMA and SDMA are eliminated from the body by renal excretion. In addition, the metabolism of ADMA, but not SDMA, occurs via hydrolytic degradation to citrulline and dimethylamine by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). Data from experimental studies suggest that ADMA inhibits vascular NO elaboration at concentrations found in pathophysiological conditions (i.e., 3-15 microM). ADMA likely acts as an autocrine regulator of endothelial NO synthase activity. When rabbits are placed on a diet enriched with 1% cholesterol, ADMA levels are increased within 4 weeks of dietary intervention as compared to control animals. Elevated plasma concentrations of ADMA are also present in hypercholesterolemic and hypertensive patients, in patients with chronic heart failure, and in other patient groups at high risk of developing cardiovascular disease. Elevation of ADMA induces dysfunction of the endothelium, which becomes clinically evident by impaired endothelium-dependent vasodilation, hyperaggregability of platelets, and enhanced monocyte adhesion. Recent prospective studies suggest that endothelial dysfunction indicates an increased risk of future cardiovascular events. In line with these observations, we and others found evidence that ADMA is a novel cardiovascular risk factor.     

Origins of circulating endothelial cells and endothelial outgrowth from blood

Normal adults have a small number of circulating endothelial cells (CEC) in peripheral blood, and endothelial outgrowth has been observed from cultures of blood. In this study we seek insight into the origins of CEC and endothelial outgrowth from cultures of blood. Fluorescence in situ hybridization analysis of blood samples from bone marrow transplant recipients who had received gender-mismatched transplants 5-20 months earlier showed that most CEC in fresh blood had recipient genotype. Endothelial outgrowth from the same blood samples after 9 days in culture (5-fold expansion) was still predominantly of the recipient genotype. In contrast, endothelial outgrowth after approximately 1 month (102-fold expansion) was mostly of donor genotype. Thus, recipient-genotype endothelial cells expanded only approximately 20-fold over this period, whereas donor-genotype endothelial cells expanded approximately 1000-fold. These data suggest that most CEC in fresh blood originate from vessel walls and have limited growth capability. Conversely, the data indicate that outgrowth of endothelial cells from cultures of blood is mostly derived from transplantable marrow-derived cells. Because these cells have more delayed outgrowth but a greater proliferative rate, our data suggest that they are derived from circulating angioblasts.     

Asymmetric dimethylarginine and total homocysteine in plasma after oral methionine loading

Background: Elevation of homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) in plasma are believed to be involved in the pathogenesis of cardiovascular disease (CVD). In humans, oral methionine loading results in acute elevation of plasma Hcy. This is associated with impaired NO‐dependent vasodilatation, a mechanism that may explain the relationship between elevated Hcy and risk of CVD. ADMA, an endogenous competitive inhibitor of NO‐synthase, may be elevated in plasma of patients with CVD. It was proposed that ADMA is synthesized in a methionine‐dependent reaction which also forms Hcy. In this study plasma total homocysteine (tHcy) and ADMA concentrations were measured before and after oral methionine loading of human subjects. Methods: Plasma tHcy and ADMA levels were measured in 12 healthy males (age 32–58 years) before and after oral loading with L‐methionine (100?mg/kg body weight in orange juice). Results: At noon, 4?h after methionine loading, tHcy and ADMA levels (35.4±10.9 and 0.80±0.13?μmol/L, mean ±SD) were significantly higher than the corresponding values obtained at noon the day before (15.6±7.4 and 0.63±0.10?μmol/L, both p<0.001). Noon values 4?h after methionine loading were also significantly higher than values obtained immediately before the methionine load (13.7±5.9 and 0.66±0.10?μmol/L, both p<0.001). Reinvestigation of 8 of 12 subjects showed that at 4 and 8?h after compared with levels immediately before methionine loading there was a significant increase in tHcy (28.4±10.2 and 33.45±11.1 vs. 10.8±3.3?μmol/L, both p<0.001). However, the corresponding ADMA levels did not increase (0.73±0.17 and 0.76±0.22 vs. 0.70±0.10?μmol/L, both not significant). Conclusions: No clear evidence was found to support the supposition that methionine‐induced hyperhomocysteinaemia may be accompanied by elevated levels of ADMA, an endogenous competitive NO‐synthase inhibitor that may represent an alternative pathogenic mechanism for homocysteine‐associated impairment of endothelial NO‐dependent functions.     

Asymmetric dimethylarginine, homocysteine and renal function--is there a relation?

The adverse effect of hyperhomocysteinemia on the vascular wall can be partially explained by increasing plasma concentration of asymmetric dimethylarginine (ADMA), a potent inhibitor of nitric oxide synthase. The aim of the study was to compare ADMA and homocysteine levels in three groups of subjects: blood donors with normal homocysteine concentration (group A), patients with hyperhomocysteinemia and normal kidney function (group B) and hemodialysis patients who are known to be hyperhomocysteinemic (group C). Concentrations of homocysteine (enzymatic method), ADMA (enzyme-linked immunoassay) and creatinine (Jaffe method) in EDTA plasma were measured. Plasma ADMA levels were significantly higher in both groups with hyperhomocysteinemia (1.60+/-0.56 micromol/L in group B, 1.81+/-0.57 micromol/L in group C) when compared with those in blood donors (0.82+/-0.29 micromol/L, p<0.001 in both cases). Significant positive correlations were found between concentrations of ADMA and homocysteine (r=0.42, p<0.0001), ADMA and creatinine (r=0.39 p<0.001), homocysteine and creatinine (r=0.69, p<0.0001), age and homocysteine (r=0.47, p<0.001), age and ADMA (r=0.57, p<0.001) and age and creatinine (r=0.37, p<0.001). Increased ADMA concentrations in hyperhomocysteinemic patients were confirmed, but multiple linear regression analysis showed that this significant correlation is only apparent due the dependence of both parameters on age.     

Asymmetric dimethylarginine and total homocysteine in plasma after oral methionine loading

BACKGROUND: Elevation of homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) in plasma are believed to be involved in the pathogenesis of cardiovascular disease (CVD). In humans, oral methionine loading results in acute elevation of plasma Hcy. This is associated with impaired NO-dependent vasodilatation, a mechanism that may explain the relationship between elevated Hcy and risk of CVD. ADMA, an endogenous competitive inhibitor of NO-synthase, may be elevated in plasma of patients with CVD. It was proposed that ADMA is synthesized in a methionine-dependent reaction which also forms Hcy. In this study plasma total homocysteine (tHcy) and ADMA concentrations were measured before and after oral methionine loading of human subjects. METHODS: Plasma tHcy and ADMA levels were measured in 12 healthy males (age 32-58 years) before and after oral loading with L-methionine (100 mg/kg body weight in orange juice). RESULTS: At noon, 4 h after methionine loading, tHcy and ADMA levels (35.4 +/- 10.9 and 0.80 +/- 0.13 micromol/L, mean +/- SD) were significantly higher than the corresponding values obtained at noon the day before (15.6 +/- 7.4 and 0.63 +/- 0.10 micromol/L, both p<0.001). Noon values 4 h after methionine loading were also significantly higher than values obtained immediately before the methionine load (13.7 +/- 5.9 and 0.66 +/- 0.10 micromol/L, both p<0.001). Reinvestigation of 8 of 12 subjects showed that at 4 and 8 h after compared with levels immediately before methionine loading there was a significant increase in tHcy (28.4 +/- 10.2 and 33.45 +/- 11.1 vs. 10.8 +/- 3.3 micromol/L, both p<0.001). However, the corresponding ADMA levels did not increase (0.73 +/- 0.17 and 0.76 +/- 0.22 vs. 0.70 +/- 0.10 micromol/L, both not significant). CONCLUSIONS: No clear evidence was found to support the supposition that methionine-induced hyperhomocysteinaemia may be accompanied by elevated levels of ADMA, an endogenous competitive NO-synthase inhibitor that may represent an alternative pathogenic mechanism for homocysteine-associated impairment of endothelial NO-dependent functions.     

Lycopene affects proliferation and apoptosis of four malignant cell lines.

The beneficial effect of lycopene from tomatoes on a variety of chronic diseases and particularly its association with decreased incidence of prostate and breast cancer seems to be well established. The aim of the study was to examine its anti-proliferative and apoptotic effect on other malignant cell lines. Cells of the following lines were incubated with 1.0, 2.0, and 4.0microM of lycopene: human colon carcinoma (HuCC), B chronic lymphocytic leukemia (EHEB), human erythroleukemia (K562) and Raji, a prototype of Burkitt lymphoma cell line. The results showed that lycopene exerted a significant dose-dependent effect on the proliferation capacity of K562, Raji and HuCC lines, whereas this effect was observed in EHEB cells only with the highest dose used in the study. Increased apoptotic rate was found after incubation of HuCC cells with 2.0 and 4.0microM of lycopene and in Raji cells following incubation with 2.0microM. The findings point out that the anti-proliferative effect of lycopene on tumor cells and its effect on the apoptotic rate depends on its dosage and on the type of the malignant cells.     

Oxidized LDL activates fas-mediated endothelial cell apoptosis.

Oxidized low density lipoproteins (OxLDL) promote chronic inflammatory responses in the vasculature that give rise to atherosclerotic plaques. Fas ligand (FasL) is naturally expressed on the vascular endothelium where it can induce apoptosis in Fas-expressing immune cells as they enter the vessel wall. Although vascular endothelial cells are normally resistant to Fas-mediated cell death, OxLDL were shown to induce apoptosis in cultured endothelial cells and endothelium of arterial explants by a process that could be inhibited with Fas L neutralizing antibodies. OxLDL-induced cell death was also reduced in the aortic endothelium cultured from gld (FasL-/-) and lpr (Fas-/-) mice as compared with wild-type mice. OxLDL acted by sensitizing endothelial cells to death signals from the Fas receptor. Thus, the ability of OxLDL to promote Fas-mediated endothelial cell suicide may be a feature that contributes to their atherogenicity.     

Asymmetric dimethylarginine concentration and early recurrence of atrial fibrillation after electrical cardioversion

Background: The purpose of this study was to determine whether high asymmetric dimethylarginine (ADMA) levels could predict early recurrence of atrial fibrillation (AF) after successful electrical cardioversion (CV).
Methods : Seventy patients with persistent AF, but without known heart disease, who underwent elective electrical CV were enrolled. Blood samples for ADMA determination were drawn from all patients just before the CV.
Results : The study population comprised 64 patients (men 73%, age 62.56 ± 7.72 years, duration of AF 6.00 ± 1.90 months) in whom sinus rhythm was restored. After 1-month follow-up, 30 (47%) patients had recurrence of AF. The median ADMA concentration was significantly higher in patients with AF recurrence (1.93 μmol/L vs 1.43 μmol/L; P = 0.001). AF recurrence was associated with higher pre-CV ADMA levels (odds ratio [OR]= 4.20; 95% confidence interval [CI], 1.44–12.22; P = 0.001). On multivariate analysis, ADMA was the only independent predictor of arrhythmia recurrence (OR = 4.19; 95%CI, 1.12–15.77; P = 0.034).
Conclusion : Our data suggest that high levels of ADMA are associated with an increased risk of AF recurrence within 1 month after electrical CV, supporting the hypothesis that ADMA might participate in the process of atrial remodeling.