迷迭香酸抗动脉粥样硬化作用研究

本研究主要研究迷迭香酸是否能改善动脉粥样硬化(AS)。采用平行板流动腔模拟低剪切力(LSS)建立内皮细胞功能紊乱模型,使用DHE和DAF-FM DA探针检测细胞中ROS和NO的活性,分别使用qPCR法和Western blotting检测细胞中ICAM-1和VCAM-1的mRNA和蛋白表达来反应细胞炎症反应。采用高脂饲料(HCD)喂食斑马鱼建立斑马鱼AS模型,并在荧光显微镜下观察AS斑马鱼的脂质蓄积、炎症和氧化应激。结果发现,LSS诱导严重的内皮细胞功能紊乱,主要表现为:内皮细胞中ROS活性、ICAM-1和VCAM-1的mRNA和蛋白表达显著升高,而NO的活性显著降低。迷迭香酸的治疗可以有效改善LSS诱导的这些内皮细胞功能紊乱现象。结果也发现,HCD显著增加斑马鱼低剪切力处血管中的脂质蓄积,同时也诱导斑马鱼发生氧化应激和炎症反应。迷迭香酸治疗可以显著改善HCD诱导的这些AS症状。综上所述,迷迭香酸可以有效改善AS,并且其治疗AS的作用可能与其改善LSS诱导的内皮细胞功能紊乱作用有关。     

氰酸盐诱导人脐静脉内皮细胞氧化应激损伤

该研究探讨尿素水解产物氰酸盐(cyanate)对体外培养的血管内皮细胞氧化应激和功能障碍的作用。培养人脐静脉内皮细胞系(human umbilical vein endothelial cells,HUVECs),通过CCK8法检测氰酸盐对内皮细胞活力的影响;采用DCFH-DA法检测ROS水平;用比色法测定NO水平;分别用细胞免疫荧光和Western blot检测ICAM-1(intercelluar adhesion molecule-1)、e NOS(endothelial nitric oxide synthase)表达。氰酸盐呈浓度依赖性影响内皮细胞活力,与对照组相比,当氰酸盐浓度为1.00 mmol/L时,细胞活力受到明显抑制(P0.05);与正常组和阴性对照组(甘露醇组)相比,氰酸盐诱导内皮细胞内ROS水平明显升高;NO水平明显减少(P0.05)。免疫荧光结果显示,氰酸盐作用内皮细胞24 h后,ICAM-1荧光明显增强,e NOS明显减弱(P0.05)。Western blot结果显示,内皮细胞内ICAM-1水平随氰酸盐浓度升高和负荷时间延长上调,而e NOS水平下调(P0.05)。氰酸盐诱导血管内皮细胞氧化应激产生和功能障碍。     

白细胞与内皮细胞的粘附

白细胞与内皮细胞相互作用由粘附分子介导.整合素、免疫球蛋白及选择素家族的粘附分子在这两种细胞的粘附中起关键作用.粘附的起始阶段由选择素介导,随后由CD11/CD18复合物与ICAM-1形成更为紧密的结合.多种细胞因子及炎症反应可诱导粘附.抗粘附分子单抗、药物等可抑制粘附.     

肿瘤坏死因子alpha与子痫前期的关系

子痫前期是妊娠期特有疾病,是导致孕产妇及围生儿病死率的重要原因,其病因和发病机理仍未完全明确。目前,已被提出 和子痫前期的发生相关的因素包括遗传、氧化应激、异常滋养层细胞侵入、血管内皮细胞功能紊乱、营养缺乏、免疫缺陷等,其中 内皮细胞损伤导致的内皮细胞生理功能紊乱已经成为子痫前期病因学研究的热点。肿瘤坏死因子-alpha(tumor necrosis factor-alpha, TNF-alpha)在内皮细胞损害中发挥着重要作用,可能通过诱导炎性因子和血管内皮细胞黏附分子-1(VCAM-1)生成、抑制基质金属蛋 白酶(MMP)、影响血管活性物质、脂联素、瘦素和血管因子生成,介导子痫前期的发生。本文就TNF-琢与子痫前期发生的关系进行 综述。     

肥胖2型糖尿病患者血清脂联素、E-选择素、可溶性细胞黏附因子-1的表达及其与氧化应激的关系

目的:研究肥胖2型糖尿病患者血清脂联素、E-选择素、可溶性细胞黏附因子-1的表达及其与氧化应激的关系。方法:选择2015年06月至2017年01月在我院治疗的2型糖尿病患者72名,根据患者体重和腰围分为观察组与对照组,观察组为肥胖2型糖尿病患者,对照组为非肥胖2型糖尿病患者。分析两组患者临床指标检测结果及与氧化应激的相关性。结果:观察组血清脂联素(Adiponectin,ADPN)、超氧化物歧化酶(Superoxide Dismutase,SOD)水平[(6.05±1.01)μg/ml vs(7.83±1.25)μg/ml、(72.15±12.04)NU/ml vs(87.66±14.53) NU/ml]均明显低于对照组水平,且观察组E-选择素(Human soluble E-selectin, s E-selectin)、丙二醛(Malondialdehyde; malonic dialdehyde; Propanedial, MDA)、可溶性血管细胞黏附因子-1 (Human soluble vasccular cell adhesion molecule 1, s VCAM-1)、HOMA-胰岛素抵抗指数(Homeostasis model assessment for insulin resistance, HOMA-IR)水平[(66.81±11.10)μg/L vs (55.22±9.05)μg/L、(5.68±0.92)μmol/L vs (4.15±0.62)μmol/L、(1.84±0.25) mg/L vs (1.70±0.24) mg/L、(4.52±1.88) vs(2.23±1.15)]均明显高于对照组(P0.05);观察组患者甘油三酯(Triglyceride,TG)、胆固醇(total cholesterol, TC)、低密度脂蛋白胆固醇(Low-density lipoprotein, LDL-C)显著高于对照组,高密度脂蛋白胆固醇(High-density lipoprotein cholesterol, HDL-C)、糖化血红蛋白(Hemoglobin A1C, HbA1C)明显低于对照组(P0.05)。MDA与空腹血糖(fasting plasma glucose, FPG)、餐后2小时血糖(2 hours postprandial blood glucose, 2Hpg)、HbA1C、TG、TC、LDL-C、s E-selectin、s VCAM-1、HOMA-IR呈正相关关系(P0.05),与HDL3-C、ADPN、SOD呈负相关关系(P0.05);SOD与FPG、2Hpg、Hb A1C、TG、TC、LDL-C、s E-selectin、s VCAM-1、HOMA-IR、MDA呈负相关关系(P0.05),与HDL3-C、ADPN呈正相关关系(P0.05)。结论:肥胖易导致2型糖尿病患者的血清脂联素下降并抑制胰岛素的分泌,可溶性血管细胞黏附分子-1及E-选择素的高表达与肥胖2型糖尿病患者发生氧化应激有关。     

肿瘤坏死因子α与子痫前期的关系

子痫前期是妊娠期特有疾病,是导致孕产妇及围生儿病死率的重要原因,其病因和发病机理仍未完全明确。目前,已被提出和子痫前期的发生相关的因素包括遗传、氧化应激、异常滋养层细胞侵入、血管内皮细胞功能紊乱、营养缺乏、免疫缺陷等,其中内皮细胞损伤导致的内皮细胞生理功能紊乱已经成为子痫前期病因学研究的热点。肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)在内皮细胞损害中发挥着重要作用,可能通过诱导炎性因子和血管内皮细胞黏附分子-1(VCAM-1)生成、抑制基质金属蛋白酶(MMP)、影响血管活性物质、脂联素、瘦素和血管因子生成,介导子痫前期的发生。本文就TNF-α与子痫前期发生的关系进行综述。     

蒺藜皂苷对糖基化终产物形成及其诱导的内皮细胞功能障碍影响研究

本文探讨蒺藜皂苷(STT)对糖基化终产物(AGEs)形成及AGEs诱导的内皮细胞功能障碍的影响。以荧光法检测AGEs体外形成,MTT法检测细胞存活率,试剂盒方法检测细胞及培养上清液中的一氧化氮(NO)水平、诱导型NO合酶(iNOS)活力和超氧阴离子水平(O2-.)。结果显示STT促进AGEs形成,并加剧AGEs诱导的内皮细胞生长抑制,提高细胞NO分泌,增加iNOS活力和O2-.水平。与海可、替告皂苷元作用进行比较,发现STT的细胞损伤作用可能是海可皂苷元引起的。提示STT未能抑制体外AGEs形成,对AGEs引起的内皮细胞功能障碍无明显保护作用,反而可能通过增强iNOS酶活加剧细胞损伤。     

SURZB/Kir6.1通道开放剂纳他卡林对低氧致大鼠主动脉内皮细胞损伤的保护作用

目的:探讨纳他卡林对低氧引起大鼠主动脉内皮细胞损伤的保护作用及其机制。方法:选取大鼠主动脉内皮细胞作为体外低氧损伤的细胞模型,分为正常对照组、低氧模型组、纳他卡林低、中、高剂量组,利用MTT法测定细胞生存率,硝酸还原酶法检测一氧化氮(NO)释放,RT-PCR法检测细胞间粘附因子-1(ICAM-1)、内皮素-1(ET-1)、血管内皮生长因子(VEGF)mRNA水平。结果:纳他卡林三个剂量组均可逆转低氧所致的血管内皮细胞功能改变,包括提高内皮细胞生存活力和NO的释放水平,显著抑制低氧引发的内皮细胞ICAM-1,ET-1,VEGF mRNA表达量的上调。结论:纳他卡林对低氧诱发的血管内皮细胞分泌功能改变、细胞通透性增加及炎性因子的分泌均具有保护作用。     

BET蛋白通过调控NF-κB通路参与炎症基因转录

目的:探讨特异性抑制溴结构域(bromodomain and extra-terminal,BET)蛋白对血管内皮细胞激活与早期动脉粥样硬化形成的作用及其分子机制。方法:1.原代分离培养脐静脉内皮细胞和小鼠心脏血管内皮细胞后用肿瘤坏死因α(TNFα)刺激模拟炎症过程,以小分子化合物JQ1特异性抑制BET蛋白,分组如下:(1)对照组;(2)TNFα(25 ng/m L)处理组;(3)TNFα+JQ1处理组。采用Realtime-PCR及流式细胞术检测各组细胞炎症因子m RNA及蛋白水平的表达,采用5XκB荧光素酶报告基因检测各组核转录因子kappa B(NF-κB)转录活性。2.LDL受体基因敲除(LDLR-/-)小鼠随机分为2组:JQ1组(n=8,JQ1腹腔注射,50 mg/kg,每天一次)和对照组(n=8,DMSO溶媒组),同时给予高胆固醇饮食8周,采用免疫组化方法检测主动脉弓部血管细胞黏附分子-1(VCAM-1)表达水平。结果:与对照组相比,TNFα组炎症因子m RNA、蛋白表达明显上调(P0.01),使用JQ1干预后,炎症因子E选择素(E-selectin)、P选择素(P-selectin)、VCAM-1及白细胞介素-8(IL-8)m RNA及蛋白表达均明显下调(P0.01)。LDLR-/-小鼠高脂饮食诱导8周后JQ1显著下调了主动脉弓部VCAM-1蛋白表达。5XκB荧光素酶报告基因结果显示,与TNFα(-)相比,TNFα(+)组荧光素酶报告基因活性增强,JQ1可以显著下调报告基因活性(P0.01)。结论:BET蛋白通过调控NF-κB信号通路参与了血管内皮炎症基因转录;抑制BET蛋白下调了NF-κB目的基因表达从而减轻了内皮激活及高脂诱导的早期动脉粥样硬化病理改变。     

瑞舒伐他汀与阿托伐他汀对冠心病高脂血症患者血脂及血浆ADMA水平的影响

目的:探讨瑞舒伐他汀与阿托伐他汀对冠心病高脂血症患者血脂及血浆不对称二甲基精氨酸(ADMA)水平的影响。方法:选取2016年3月-2017年12月四川大学华西医院收治的冠心病高脂血症患者210例为研究对象,随机分为研究组与对照组,每组各105例,研究组患者给予瑞舒伐他汀治疗,对照组给予阿托伐他汀治疗,均连续治疗8周。比较两组患者治疗前及治疗8周后血脂水平、ADMA水平及血清炎症因子水平、血管内皮功能指标水平,记录两组患者的不良反应发生情况。结果:两组患者治疗前及治疗8周后甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平比较无统计学差异(P0.05),两组患者治疗8周后TG、TC、LDL-C水平均较治疗前降低(P0.05),而HDL-C水平与治疗前相比无统计学差异(P0.05)。两组患者治疗8周后ADMA、超敏C反应蛋白(hs-CRP)、白介素-6(IL-6)水平均较治疗前降低,且研究组低于对照组(P0.05)。治疗8周后两组患者内皮素-1(ET-1)水平较治疗前降低,一氧化氮(NO)水平较治疗前升高(P0.05),且研究组患者ET-1水平低于对照组,NO水平高于对照组(P0.05)。研究组与对照组患者在治疗期间均未发生难以耐受的不良反应。结论:与阿托伐他汀相比,应用瑞舒伐他汀治疗冠心病高脂血症患者可改善血管内皮功能和TG、TC、LDL-C水平,减轻炎症反应,降低ADMA水平,无严重不良反应发生,值得临床推广。     

Haemoglobin-induced oxidative stress is associated with both endogenous peroxidase activity and H2O2 generation from polyunsaturated fatty acids

Patients with increased haemolytic haemoglobin (Hb) have 10-20-times greater incidence of cardiovascular mortality. The objective of this study was to evaluate the role of Hb peroxidase activity in LDL oxidation. The role of Hb in lipid peroxidation, H(2)O(2) generation and intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was assessed using NaN(3), a peroxidase inhibitor, catalase, a H(2)O(2) decomposing enzyme and human umbilical vein endothelial cells (HUVECs), respectively. Hb induced H(2)O(2) production by reacting with LDL, linoleate and cell membrane lipid extracts. Hb-induced LDL oxidation was inhibited by NaN(3) and catalase. Furthermore, Hb stimulated ICAM-1 and VCAM-1 expression, which was inhibited by the antioxidant, probucol. Thus, the present study suggests that the peroxidase activity of Hb produces atherogenic, oxidized LDL and oxidized polyunsaturated fatty acids (PUFAs) in the cell membrane and reactive oxygen species (ROS) formation mediated Hb-induced ICAM-1 and VCAM-1 expression.     

The 18-kDa Translocator Protein Inhibits Vascular Cell Adhesion Molecule-1 Expression via Inhibition of Mitochondrial Reactive Oxygen Species

Translocator protein 18 kDa (TSPO) is a mitochondrial outer membrane protein and is abundantly expressed in a variety of organ and tissues. To date, the functional role of TSPO on vascular endothelial cell activation has yet to be fully elucidated. In the present study, the phorbol 12-myristate 13-acetate (PMA, 250 nM), an activator of protein kinase C (PKC), was used to induce vascular endothelial activation. Adenoviral TSPO overexpression (10–100 MOI) inhibited PMA-induced vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) expression in a dose dependent manner. PMA-induced VCAM-1 expressions were inhibited by Mito-TEMPO (0.1–0.5 μM), a specific mitochondrial antioxidants, and cyclosporin A (1–5 μM), a mitochondrial permeability transition pore inhibitor, implying on an important role of mitochondrial reactive oxygen species (ROS) on the endothelial activation. Moreover, adenoviral TSPO overexpression inhibited mitochondrial ROS production and manganese superoxide dismutase expression. On contrasts, gene silencing of TSPO with siRNA increased PMA-induced VCAM-1 expression and mitochondrial ROS production. Midazolam (1–50 μM), TSPO ligands, inhibited PMA-induced VCAM-1 and mitochondrial ROS production in endothelial cells. These results suggest that mitochondrial TSPO can inhibit PMA-induced endothelial inflammation via suppression of VCAM-1 and mitochondrial ROS production in endothelial cells.     

7-Ketocholesterol enhances the expression of adhesion molecules on human aortic endothelial cells by increasing the production of reactive oxygen species

Abstract

The aim of the present study was to assess the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), monocytic adhesion of human aortic endothelial cells (HAECs), and the production of intracellular reactive oxygen species (ROS), when HAECs were stimulated by 7-ketocholesterol. 7-ketocholesterol enhances surface expression of ICAM-1 and VCAM-1 as determined by EIA, induces their mRNA expression by RT-PCR, and stimulates adhesiveness of HAECs to U937 monocytic cells. We confirmed up-regulation of ROS production of HAECs treated with 7-ketocholesterol. Although the surface expression of ICAM-1 and VCAM-1 on HAECs treated with 7-ketocholesterol increased in a time-dependent manner, α-tocopherol inhibited this increase of the surface expression of ICAM-1 and VCAM-1. In the monocytic adhesion assay, adhesion of U937 to HAECs treated with 7-ketocholesterol was enhanced, but monoclonal anti-ICAM-1 and VCAM-1 antibodies reduced the endothelial adhesiveness. In conclusion, this study suggests that the endothelial adhesiveness to monocytic cells that was increased by 7-ketocholesterol was associated with enhanced expression of ICAM-1 and VCAM-1 mediated by ROS production.     

Glucose-dependent insulinotropic polypeptide (GIP) inhibits signaling pathways of advanced glycation end products (AGEs) in endothelial cells via its antioxidative properties

Glucose-dependent insulinotropic polypeptide (GIP) is one of the incretins, a gut hormone secreted from K cells in the intestine in response to food intake. It could be a potential therapeutic target for the treatment of patients with type 2 diabetes. However, effects of GIP on vascular injury remain unknown. Since interaction of advanced glycation end products (AGEs) with their receptor RAGE has been shown to play a crucial role in vascular damage in diabetes, this study investigated whether and how GIP blocked the deleterious effects of AGEs on human umbilical vein endothelial cells (HUVECs). GIP receptor was expressed in HUVECs. GIP, an analogue of cyclic AMP or inhibitors of NADPH oxidase inhibited the AGE-induced reactive oxygen species (ROS) generation in HUVECs. Furthermore, GIP reduced both RAGE mRNA and protein levels in HUVECs. GLP-1 also blocked the AGE-induced increase in mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and plasminogen activator inhibitor-1 in HUVECs. In addition, an antioxidant N-acetylcysteine mimicked the effects of GIP on RAGE and VCAM-1 gene expression in HUVECs. Our present study suggests that GIP could block the signal pathways of AGEs in HUVECs by reducing ROS generation and subsequent RAGE expression probably via GIP receptor-cyclic AMP axis.     

Cryptotanshinone inhibits oxidized LDL-induced adhesion molecule expression via ROS dependent NF-κB pathways

Adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, play important roles in the initial stage of atherosclerosis. Cryptotanshinone (CPT), a natural compound isolated from Salvia miltiorrhiza Bunge, exhibits anti-atherosclerotic activity although the underlying mechanisms remain elusive. In this study, the protective effect of CPT against oxidized low-density lipoprotein (ox-LDL)-induced adhesion molecule expression was investigated in human umbilical vein endothelial cells. Ox-LDL significantly induced ICAM-1, VCAM-1, and E-selectin expression at the mRNA and protein levels but reduced eNOS phosphorylation and NO generation, which were reversed by CPT pretreatment. Sodium nitroprusside, a NO donor, N-acetyl-L-cysteine (NAC), a reactive oxygen species (ROS) scavenger, and BAY117082, a NF-κB inhibitor, inhibited ox-LDL-induced ICAM-1, VCAM-1, and E-selectin expression. Ox-LDL-induced ROS production was significantly inhibited by CPT and NAC. Furthermore, ox-LDL activated the NF-κB signaling pathway by inducing phosphorylation of IKKβ and IκBα, promoting the interaction of IKKβ and IκBα, and increasing p65 nuclear translocation, which were significantly inhibited by CPT. In addition, CPT, NAC, and BAY117082 inhibited ox-LDL-induced membrane expression of ICAM-1, VCAM-1, E-selectin, and endothelial–monocyte adhesion and restored eNOS phosphorylation and NO generation. Results suggested that CPT inhibited ox-LDL-induced adhesion molecule expression by decreasing ROS and inhibiting the NF-κB pathways, which provides new insight into the anti-atherosclerotic mechanism of CPT.     

7-Ketocholesterol enhances the expression of adhesion molecules on human aortic endothelial cells by increasing the production of reactive oxygen species

The aim of the present study was to assess the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), monocytic adhesion of human aortic endothelial cells (HAECs), and the production of intracellular reactive oxygen species (ROS), when HAECs were stimulated by 7-ketocholesterol. 7-ketocholesterol enhances surface expression of ICAM-1 and VCAM-1 as determined by EIA, induces their mRNA expression by RT-PCR, and stimulates adhesiveness of HAECs to U937 monocytic cells. We confirmed up-regulation of ROS production of HAECs treated with 7-ketocholesterol. Although the surface expression of ICAM-1 and VCAM-1 on HAECs treated with 7-ketocholesterol increased in a time-dependent manner, alpha-tocopherol inhibited this increase of the surface expression of ICAM-1 and VCAM-1. In the monocytic adhesion assay, adhesion of U937 to HAECs treated with 7-ketocholesterol was enhanced, but monoclonal anti-ICAM-1 and VCAM-1 antibodies reduced the endothelial adhesiveness. In conclusion, this study suggests that the endothelial adhesiveness to monocytic cells that was increased by 7-ketocholesterol was associated with enhanced expression of ICAM-1 and VCAM-1 mediated by ROS production.     

HIV-1 Tat protein-induced VCAM-1 expression in human pulmonary artery endothelial cells and its signaling

Expression of cell adhesion molecule in endothelial cells upon activation by human immunodeficiency virus (HIV) infection is associated with the development of atherosclerotic vasculopathy. We postulated that induction of vascular cell adhesion molecule-1 (VCAM-1) by HIV-1 Tat protein in endothelial cells might represent an early event that could culminate in inflammatory cell recruitment and vascular injury. We determined the role of HIV-1 Tat protein in VCAM-1 expression in human pulmonary artery endothelial cells (HPAEC). HIV-1 Tat protein treatment significantly increased cell-surface expression of VCAM-1 in HPAEC. Consistently, mRNA expression of VCAM-1 was also increased by HIV-1 Tat protein as measured by RT-PCR. HIV-1 Tat protein-induced VCAM-1 expression was abolished by the NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC) and the p38 MAPK inhibitor SB-203580. Furthermore, HIV-1 Tat protein enhanced DNA binding activity of NF-kappaB, facilitated nuclear translocation of NF-kappaB subunit p65, and increased production of reactive oxygen species (ROS). Similarly to VCAM-1 expression, HIV-1 Tat protein-induced NF-kappaB activation and ROS generation were abrogated by PDTC and SB-203580. These data indicate that HIV-1 Tat protein is able to induce VCAM-1 expression in HPAEC, which may represent a pivotal early molecular event in HIV-induced vascular/pulmonary injury. These data also suggest that the molecular mechanism underlying the HIV-1 Tat protein-induced VCAM-1 expression may involve ROS generation, p38 MAPK activation, and NF-kappaB translocation, which are the characteristics of pulmonary endothelial cell activation.     

Effect of high glucose concentrations on expression of ELAM-1, VCAM-1 and ICAM-1 in HUVEC with and without cytokine activation

Diabetes mellitus is associated with an increased prevalence of endothelial dysfunction and development of atherosclerotic vascular diseases. We demonstrate here that hyperglycemia results in the expression of adhesion molecules on endothelial cells in vitro. Incubation of human umbilical vein endothelial cells (HUVEC) in a culture medium with 11.0 mM, 16.5 mM and 22.0 mM glucose concentrations induced the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial-leukocyte adhesion molecule-1 (ELAM-1). This effect was detectable after 24 h incubation of HUVEC with a high glucose concentration. The effect of high glucose concentration on TNF-alpha induced expression of ELAM-1, VCAM-1 and ICAM-1 was negligible, if at all. These results show that even a short-term exposure of endothelial cells (ECs) to high glucose concentration leads to their activation associated with increased expression of adhesion molecules such as ELAM-1, VCAM-1 and ICAM-1.