咖啡酸苯乙酯对激活的大鼠血管平滑肌细胞增殖的抑制作用

目的探讨脂多糖（lipopolysaccharide,LPS）激活血管平滑肌细胞（vascular smooth muscle cells,VSMC）后,咖啡酸苯乙酯（caffeic acid phenethyl ester,CAPE）对细胞过度增殖的影响。方法采用不同浓度的CAPE处理LPS激活的VSMC。MTT法用于检测细胞的生长情况;免疫细胞化学法检测增殖核抗原（PCNA）和存活素（Survivin）蛋白的阳性率;流式细胞仪检测细胞周期分布。结果5、10、20、40、80 mg/L CAPE处理LPS激活的VSMC后,MTT检测发现细胞的生长明显受到抑制并呈剂量和时间依赖;VSMC经CAPE处理72 h后,细胞中PCNA和Survivin蛋白阳性表达率随药物剂量增加而显著降低（P<0.05）;细胞周期分析表明5、10、20 mg/L CAPE处理VSMC 24 h后,对照组和实验组G0/G1期细胞百分率分别为（40±4.3）%和（52±6）%,（65±1）%,（76±4）%,S期细胞百分率由对照组的（32.4%±2.6）%逐渐下降20 mg/L组的（11.2%±1.4）%,呈剂量依赖性（P<0.05）。结论CAPE可能通过调控细胞周期,减少PCNA和Survivin蛋白的表达而发挥细胞增殖抑制作用,其效能与作用时间和药物剂量存在一定的相关性。     

糖皮质激素对脂多糖诱导小鼠巨噬细胞增殖和细胞因子的影响

目的：探讨脂多糖(LPS)和长期大剂量应用地塞米松对小鼠巨噬细胞RAW264.7增殖活化及细胞因子表达的影响。方法不同剂量地塞米松(10、50、100、150 mg/L)作用于小鼠巨噬细胞RAW264.724 h 后,1 mg/L LPS 再作用于细胞24 h,应用 CCK-8检测RAW264.7细胞增殖情况,ELISA检测炎症因子 IL-6和趋化因子 IL-8的表达水平。结果1 mg/L LPS 促进RAW264.7细胞增殖并激活细胞产生大量 IL-6和 IL-8,不同剂量地塞米松干预细胞24 h 后,RAW264.7细胞增殖情况受到抑制,呈浓度依赖性。炎症因子 IL-6和趋化因子 IL-8表达水平也随地塞米松浓度增加而降低。结论小剂量LPS 促进巨噬细胞增殖并活化产生大量细胞因子。而长期大剂量应用地塞米松抑制巨噬细胞的生长增殖,同时抑制炎症因子及趋化因子的表达,降低机体清除病原体的能力,造成了免疫抑制患者发生难以控制的感染。     

姜黄素对血管平滑肌细胞增殖及cyclinD1和p21wafl/cipl蛋白表达的影响

目的 观察姜黄素(curcumin)抑制大鼠血管平滑肌细胞(VSMC)增殖和诱导细胞周期停滞的作用,以及对细胞周期蛋白cyclinDl,p21wafl/cipl表达的影响.方法 采用组织贴块法体外培养大鼠VSMC,MTT法测定姜黄素对VSMC增殖的抑制作用,流式细胞仪分析细胞周期分布,Western印迹法检测cyclinDl,p21wafl/cipl蛋白的变化.结果 MTT示不同浓度姜黄素(7.5～120 μmol/L)在24～72 h范围内,浓度和时间依赖性抑制VSMC增殖;30 μmol/L以上浓度姜黄素显著抑制增殖的VSMC细胞周期进程,使S及G2/M期减少(P<0.05),G0/G1期增加(P<0.05);30 μmol/L的姜黄素可抑制cyclinDl表达,促进p21wafl/cipl蛋白表达.结论 姜黄素具有明确的抑制VSMC增殖和细胞周期停滞的作用,其与cyclinDl,p21wafl/cipl蛋白变化有关.     

泽泻汤对氧化型低密度脂蛋白诱导血管平滑肌细胞增殖的影响

目的观察泽泻汤对血管平滑肌细胞(VSMC)周期蛋白Cyclin D1、Cyclin E、增殖细胞核抗原(PCNA)和p27表达的影响,探讨泽泻汤在氧化型低密度脂蛋白(ox-LDL)诱导的VSMC增殖中的作用和机制。方法通过体外50 mg/L ox-LDL诱导VSMC,建立VSMC增殖的动脉粥样硬化细胞模型;应用空白血清及20%泽泻汤含药血清干预。MTS法检测泽泻汤含药血清对VSMC增殖的影响;Western blot检测增殖相关蛋白Cyclin D1、Cyclin E、PCNA和p27表达水平。结果 50 mg/L ox-LDL可明显诱导VSMC增殖。与ox-LDL组比较,泽泻汤含药血清可显著抑制ox-LDL诱导的VSMC增殖,下调细胞Cyclin D1、Cyclin E和PCNA的表达,同时促进p27蛋白表达。结论泽泻汤具有抗VSMC增殖的作用,机制可能与上调p27蛋白和抑制Cyclin D1、Cyclin E、PCNA表达有关。     

胆固醇对血管平滑肌细胞增殖及迁移的作用

目的探讨胆固醇对血管平滑肌细胞增殖及迁移的作用。方法体外培养人血管平滑肌细胞株(VSMC),以12.5 mg/L、25.0 mg/L、50.0 mg/L不同浓度胆固醇(CH)分别作用细胞24 h、48 h、72 h后,MTT法检测VSMC的增殖情况;流式细胞术检测细胞进入S期的数量;EDU试剂盒检测CH作用后细胞的DNA合成;划痕实验检测VSMC迁移情况;Real-time PCR检测细胞中miR145的表达水平。结果 12.5 mg/L、25.0 mg/L、50.0 mg/L CH作用VSMC后可增加细胞活力,促进细胞增殖,与对照组比较,进入S期的VSMC细胞数量明显增多,细胞迁移增加(P0.05);与对照组比较,25.0 mg/L、50.0 mg/L CH可诱导VSMC DNA合成增加,并且明显降低miR-145的表达水平(P0.05)。结论 CH可诱导VSMC进入S期细胞增多,促进细胞增殖,并且增加细胞的DNA合成及细胞迁移,其机制可能与抑制miR-145的表达有关。     

咖啡酸苯乙酯对LPS诱导大鼠KC表达细胞因子的影响

目的 观察CAPE对LPS活化大鼠KC表达合成细胞因子IL-6和TNF-α的影响.方法 经在体灌流消化大鼠肝脏分离KC细胞,培养于RPMI-1640培养基中,用LPS活化KC细胞,经CAPE处理后,用实时定量RT-PCR检测KC细胞中IL-6和TNF-α基因表达,用ELISA方法检测培养基中IL-6和TNF-α蛋白含量.结果 对于LPS诱导活化的KC细胞,CAPE剂量依赖地降低KC细胞中IL-6和TNF-α mRNA表达,分别在10 μmol/L和20 μmol/L时差异具有统计学意义,KC合成IL-6和TNF-α蛋白也显著降低.结论 CAPE具有降低LPS活化KC表达合成IL-6和TNF-α作用.     

姜黄素对血管平滑肌细胞增殖及cyclinD1和p21waf1/cip1蛋白表达的影响

目的 观察姜黄素（curcumin）抑制大鼠血管平滑肌细胞(VSMC)增殖和诱导细胞周期停滞的作用,以及对细胞周期蛋白cyclinD1,p21waf1/cip1表达的影响。方法 采用组织贴块法体外培养大鼠VSMC,MTT法测定姜黄素对VSMC增殖的抑制作用,流式细胞仪分析细胞周期分布,Western印迹法检测cyclinD1,p21waf1/cip1蛋白的变化。结果 MTT示不同浓度姜黄素(7.5～120 μmol/L)在24～72 h范围内,浓度和时间依赖性抑制VSMC增殖;30 μmol/L以上浓度姜黄素显著抑制增殖的VSMC细胞周期进程,使S及G2/M期减少(P<0.05),G0/G1期增加(P<0.05);30 μmol/L的姜黄素可抑制cyclinD1表达,促进p21waf1/cip1蛋白表达。结论 姜黄素具有明确的抑制VSMC增殖和细胞周期停滞的作用,其与cyclinD1,p21waf1/cip1蛋白变化有关。     

盐酸地尔硫(艹卓)对血管平滑肌细胞增殖与凋亡的影响

目的 探讨合贝爽对血管平滑肌细胞(VSMC)增殖和凋亡的影响及其作用机制.方法 将VSMC随机分为五组,分别为空白组、模型组(AngⅡ10<'-7>mol/L)和模型+合贝爽1、2、3组(剂量分别为10<'-5>、10<'-6>、10<'-7>mol/L),应用MTT法检测VSMC的生长率,TUNEL法检测凋亡率,RT-PCR检测Bcl-2、Bax、Fas和P53 mRNA的表达.结果 合贝爽抑制VSMC增殖,促进VSMC凋亡,抑制抗凋亡基因Bcl-2的表达,促进促凋亡基因Bax、Fas和P53的表达.结论 合贝爽使VSMC增殖减少,凋亡增加,其机制可能与抑制抗凋亡基因Bcl-2表达、促进促凋亡基因Bax、Fas和P53表达有关.     

MiR-92a-3p_R+1和miR-92a-1-5p在ox-LDL诱导大鼠VSMC表型转化和增殖中的作用

目的探讨miR-92a-3p_R+1和miR-92a-1-5p在氧化型低密度脂蛋白(ox-LDL)诱导大鼠血管平滑肌细胞(VSMC)表型转化和增殖中的作用及其与ERK1/2信号通路的相关性。方法分离、培养大鼠VSMC,以ox-LDL(50 mg/L)诱导VSMC,采用ERK1/2特异性抑制剂U0126(10μmol/L)阻断ox-LDL(50 mg/L)诱导VSMC的ERK1/2信号激活,MicroRNA微阵列分析VSMC的miR-92a-3p_R+1和miR-92a-1-5p表达,CCK-8法和Brdu流式细胞术检测细胞增殖;免疫荧光法检测VSMC收缩表型标志蛋白SM22α的变化;Western blot检测VSMC的ERK1/2通路信号激活情况(ERK、p-ERK)、表型标志蛋白SM22α、细胞周期相关蛋白(PCNA、cyclin D1、p21、p27)的表达情况。结果 ox-LDL诱导下,VSMC的miR-92a-3p_R+1和miR-92a-1-5p表达明显上调,VSMC的ERK1/2磷酸化水平明显增加,SM22α的表达降低,同时细胞周期相关蛋白PCNA、cyclin D1高表达,p21、p27低表达;ERK1/2通路特异性抑制剂U0126干预后,ERK1/2磷酸化水平受抑制,相应的VSMC miR-92a-3p_R+1和miR-92a-1-5p表达明显下调(P0.05),VSMC增殖显著下降,SM22α的表达上调(P0.05),提示VSMC由合成表型转化为收缩表型,并下调PCNA、cyclin D1的表达,上调p21、p27蛋白的表达(P0.05),说明其表型转化和增殖明显受抑制。结论 miR-92a-3p_R+1和miR-92a-1-5p在ox-LDL诱导VSMC表型转化和增殖中起重要作用,并与ERK1/2信号通路密切相关。     

山茱萸多糖对肺癌A549细胞凋亡的影响及机制

目的探讨山茱萸多糖对人肺癌A549细胞凋亡作用的影响及机制。方法收集对数生长期A549细胞,加入终质量浓度分别为25、50、100 mg/mL的山茱萸多糖20μL,分别培养24、48、72 h,MTT法测定细胞增殖抑制率和山茱萸多糖的半抑制浓度(IC50)。倒置显微镜下观察50 mg/mL山茱萸多糖作用后细胞形态变化。免疫组化SP法检测Survivin蛋白表达,用免疫组化评分(IHS)表示。结果山茱萸多糖作用后A549细胞生长受到明显抑制,细胞增殖抑制率呈明显的量效、时效关系;倒置显微镜下观察到细胞凋亡的典型改变,免疫组化SP法染色显示Survivin表达降低,Survivin蛋白的IHS随浓度增加呈明显下降趋势。结论山茱萸多糖能诱导A549细胞凋亡,其机制可能与下调Survivin表达有关。     

Survivin在柔红霉素诱导白血病细胞凋亡作用机制中的研究

目的：探讨Survivin在柔红霉素（DNR）作用机制中的作用,为进一步探讨白血病细胞对DNR耐药机制提供研究方向。方法：实验选用高表达Survivin的Molt-4细胞,逆转录-聚合酶链式反应（RT-PCR）检测DNR作用后Survivin mRNA的表达,免疫组织化学链霉亲和素-生物素-过氧化物酶复合物（SABC）方法检测DNR作用后Survivin蛋白的表达,免疫印迹方法检测DNR作用后Caspase-3、Caspase-8、Caspase-9蛋白的表达。结果：Survivin mRNA和蛋白表达水平随DNR浓度加大和作用时间延长而降低,差异有统计学意义（P〈0.05）;Caspase-3与Caspase-9蛋白活化片断随DNR浓度加大和作用时间延长而增多（P〈0.05）,Caspase-8未见明显活化片断。结论：①Survivin在DNR作用机制中发挥重要作用;②DNR可能通过线粒体途径诱导白血病细胞凋亡,Caspase-3和Caspase-9在凋亡通路中发挥重要作用。     

Effect of caffeic acid phenethyl ester on proliferation and apoptosis of colorectal cancer cells in vitro

ABM: To study the effect of caffeic add phenethyl ester (CAPE) on proliferation, cell cycle, apoptosis and expression of β-catenin in cultured human colorectal cancer (CRC) cell line HCT116. METHODS: HCT116 cells were treated with CAPE at serial concentrations of 80,40,20,10,5,2.5 mg/L. The proliferative status of HCT116 cells was measured by using methaben-zthiazuron (MTT) assay. Cell cycle was analyzed by using flow cytometry (FCM) with propidium iodide (PI) labeling method. The rate of apoptosis was detected by using FCM with annexin V-FITC and PI double labeling method, β-catenin levels were determined by Western blotting, β-catenin localization in HCT116 was determined by indirect immunofluorescence. RESULTS: After HCT116 cells were exposed to CAPE (80, 40, 20, 10, 5, and 2.5 mg/L) for 24, 48, 72, 96 h, CAPE displayed a strong growth inhibitory effect in a dose- and time-dependent manner against HCT116 cells. FCM analysis showed that the ratio of G0/G1 phase cells increased, S phase ratio decreased and apoptosis rate increased after HCT116 cells were exposed to CAPE (10, 5, and 2.5 mg/L) for 24 h. CAPE treatment was associated with decreased cytoplasmic β-catenin, nuclear p-catenin and a concurrent increase in β-catenin protein expression at cell-cell junctions. CONCLUSION: CAPE could inhibit HCT116 cell proliferation and induce cell cycle arrest and apoptosis. Decreased β-catenin protein expression may mediate the anti-proliferative effects of CAPE.     

葛根素对血管平滑肌细胞增殖及增殖细胞核抗原和凋亡抑制蛋白表达的影响

目的:通过观察葛根素对培养的脐动脉平滑肌细胞增殖细胞核抗原(PCNA)和凋亡抑制蛋白(Survivin)表达的影响,探讨葛根素抑制平滑肌细胞增殖的机制。方法:分离培养人脐动脉平滑肌细胞,加入不同浓度葛根素与细胞孵育,采用免疫组化法检测血管平滑肌细胞的PCNA表达;提取RNA,采用Rt-PCR检测Survivin表达水平,并经核苷酸序列分析验证,灰度扫描测定Survivin/GAPDH(s/G)比率。结果:葛根素抑制血管平滑肌细胞的PCNA表达(P=0.0000);葛根素组Survivin/磷酸甘油醛脱氢酶(GAPDH)(s/G)比率较对照组低。结论:葛根素具有抑制血管平滑肌细胞增殖的作用。     

葛根素抑制凝血酶诱导的血管平滑肌细胞增殖

目的　观察葛根素对T诱导的血管平滑肌细胞(VSMC)增殖的影响。方法　建立凝血酶(T)诱导的大鼠血管平滑肌细胞增殖模型,以细胞计数法和流式细胞仪DNA含量测定的方法观察T及葛根素对VSMC增殖和DNA合成的影响。结果　T对VSMC有明显促增殖作用,促增殖效应在2 4小时末达峰,且T浓度在0 . 1U/L～1 . 0U/L之间有剂量依赖关系;葛根素呈剂量依赖性地抑制T诱导的细胞增殖与DNA合成。结论　葛根素能抑制T诱导的VSMC增殖。     

Effect of caffeic acid phenethyl ester on proliferation and apoptosis of hepatic stellate cells in vitro

AIM: To investigate the role of nuclear factor-κB (NF-κB)inhibitor caffeic acid phenethy1 ester (CAPE) in the proliferation, collagen synthesis and apoptosis of hepatic stellate cells (HSCs) of rats. METHODS: The HSCs from rats were isolated and cultured in Dulbecco's Modified Eagle's Medium (DMEM) and treated with CAPE. The proliferation and collagen synthesis of HSCs were determined by 3H-TdR and 3H-proline incorporation respectively, and the expression of type Ⅰ, Ⅲ procollagen genes was further explored byin situ hybridization. Apoptosis cell indices (AIs) were examined using terminal deoxynucleotidyl transferase- mediated DIG-dUTP nick end labeling (TUNEL). RESULTS: Tn activated HSC in culture, CAPE significantly inhibited 3H-TdR and 3H-proline incorporation by HSCs at concentrations of 5 μmol/L and 10 μmol/L respectively. CAPE also reduced the type I procollagen gene expression (P＜0.05)at higher concentration. Apoptosis of HSC was induced by CAPE and the AIs were time-and dose-dependently increased from 2.82+0.73 % to 7.66±1.25 % at 12 h (P＜0.01) and from 3.15±0.88 % to 10.6L±2.88 % at 24 h (P＜0.01). CONCLUSION: CAPE inhibits proliferation and collagen synthesis of HSC at lower concentration and induces HSC apoptosis at higher concentration.     

Survivin is highly expressed in CD34(+)38(-) leukemic stem/progenitor cells and predicts poor clinical outcomes in AML

Survivin, a member of the inhibitors of apoptosis protein family, plays important roles in cell proliferation and survival and is highly expressed in various malignancies, including leukemias. To better understand its role in acute myeloid leukemia (AML), we profiled survivin expression in samples obtained from 511 newly diagnosed AML patients and in CD34(+)38(-) AML stem/progenitor cells using a validated reverse-phase protein array; we correlated its levels with clinical outcomes and with levels of other proteins in the same sample set. We found that survivin levels were higher in bone marrow than in paired peripheral blood leukemic cells (n = 140, P = .0001) and that higher survivin levels significantly predicted shorter overall (P = .016) and event-free (P = .023) survival in multivariate Cox model analysis. Importantly, survivin levels were significantly higher in CD34(+)38(-) AML stem/progenitor cells than in bulk blasts and total CD34(+) AML cells (P < .05). Survivin expression correlated with the expressions of multiple proteins involved with cell proliferation and survival. Particularly, its expression strongly correlated with HIF1α in the stem/progenitor cell compartment. These results suggest that survivin is a prognostic biomarker in AML and that survivin, which is overexpressed in AML stem/progenitor cells, remains a potentially important target for leukemia therapy.     

生存素反义寡核苷酸诱导肝癌细胞凋亡的实验研究

目的　生存素 (survivin)是近年来发现的凋亡抑制蛋白家族新成员 ,在多数恶性肿瘤组织中丰富表达。因此 ,观察生存素反义寡核苷酸转染对肝癌细胞凋亡、增殖、细胞对化疗药物敏感性的影响。方法　设计合成特异性靶向生存素的反义寡核苷酸 (ASODN)。肝癌细胞株hepG2 分为 6组 :空白对照组、脂质体转染对照组、正义链转染对照组、2 0 0、40 0和 6 0 0nmol/LASODN转染组。作用 2 0h后收获各组细胞。倒置显微镜观察细胞形态变化 ,Westernblot法检测各组细胞生存素表达情况 ,流式细胞术检测各组细胞增殖和凋亡指数 ,MTT法检测 5 氟尿嘧啶 (5 FU)和顺铂 (DDP)对各组细胞的生长抑制率。结果　各ASODN转染组细胞生存素表达有不同程度减弱 ,细胞变圆、折光增强、漂浮、细胞碎片形成等 ,而各对照组细胞生长良好 ;各ASODN转染组细胞凋亡指数明显高于各对照组 (P <0 .0 5 ) ,以 6 0 0nmol/L转染组最为明显 (P <0 .0 5 ) ,而各对照组间差异无显著性 (P >0 .0 5 ) ;各ASODN转染组细胞增殖指数明显低于各对照组 (P <0 .0 5 ) ,以 6 0 0nmol/L转染组最为明显 (P <0 .0 5 ) ,而各对照组间差异无显著性 (P >0 .0 5 ) ;等浓度化疗药物 5 FU和DDP对各ASODN转染组细胞的抑制率明显高于各对照组(P <0 .0 5 ) ,以 6 0 0nmol/L     

阿司匹林对血管平滑肌细胞增殖及增殖细胞核抗原表达的影响

目的探讨阿司匹林对大鼠血管平滑肌细胞增殖的影响及相关机制。方法体外培养大鼠主动脉平滑肌细胞,用不同浓度的阿司匹林处理,并且设置对照组,采用MTT法检测阿司匹林对血管平滑肌细胞增殖活性的影响,用免疫细胞化学和逆转录聚合酶链反应检测阿司匹林作用后血管平滑肌细胞中增殖细胞核抗原的表达。结果较高浓度(5×10-3mol/L)的阿司匹林对血管平滑肌细胞的增殖有明显抑制作用(P<0.05),相对抑制率为31.5%。与对照组相比,该浓度组血管平滑肌细胞中增殖细胞核抗原的蛋白和mRNA表达量均显著降低(P<0.05)。结论阿司匹林可能通过降低增殖细胞核抗原的表达来抑制血管平滑肌的增殖,对心血管系统具有抗血小板聚集之外的保护作用。     

脂多糖刺激RAW264.7和Ana-1形态改变及细胞因子表达的差异

目的 比较两株小鼠来源的巨噬细胞株RAW264.7和Ana-1经脂多糖(lipopolysaccharide,LPS)诱导后在形态及细胞因子表达等方面的差异.方法 MTT法检测小同终浓度(0.1 mg/L、1 mg/L、10 mg/L、100 mg/L)LPS作用后两株细胞增殖活力,确定最佳作用浓度.选择1 mg/L LPS刺激RAW264.7和Ana-1细胞,ELISA法分别于0 h、4 h、8 h、12 h、24 h检测两株细胞肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)、IL-6和IL-10的表达量.结果 LPS终浓度为1 mg/L时两株细胞存活率分别为(162.05±28.14)%、(159.92±20.43)%,显著大于同细胞其他浓度组别(P<0.01);1 mg/L LPS刺激后,两株细胞各细胞因子表达均为随时间呈先增多后减少趋势,峰值出现时间RAW264.7细胞早于Ana-1细胞.TNF-α的表达4 h时RAW264.7细胞高于Ana-1(P<0.01),8 h、12 h时低于后者(P<0.05);IL-1β的表达各时间点比较RAW264.7均高于Ana-1(P<0.05);IL-6的表达各时间点比较RAW264.7均低于Ana-1(P<0.05);IL-10的表达于刺激后4 h,RAW264.7细胞高于Ana-1细胞(P<0.05).结论 当LPS浓度为1 mg/L时,Ana-1与RAW264.7细胞存活率均最强;经LPS刺激后,RAW264.7细胞TNF-α、IL-6、IL-1β、IL-10表达高峰早于Ana-1细胞,各细胞因子表达量各有侧重.研究者进行炎症相关实验时对Ana-1和RAW264.7的选择需考虑两者之间的差异.     

Angiotensin II increases the expression of lectin-like oxidized low-density lipoprotein receptor-1 in human vascular smooth muscle cells via a lipoxygenase-dependent pathway

BACKGROUND: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a membrane protein that can act as a surface endocytosis receptor for oxidized LDL (ox-LDL). As increased cellular uptake of ox-LDL by macrophages and activated smooth muscle cells may transform these cells into foam cells, potential interactions among LDL oxidation, ox-LDL uptake, and regulators of vascular smooth muscle cell function are of obvious interest. The objective of this study was to examine the effect of angiotensin II (AII) on the expression of LOX-1 and ox-LDL degradation in human vascular smooth muscle cells (VSMC) METHODS: We performed in vitro experiments in a human VSMC line (T/G HA-VSMC) derived from normal aortic VSMC, using standards methods. RESULTS: We found that AII (10(-7) mol/L) increased the expression of LOX-1 (approximately 2.5-fold, P < .0001) in association with higher degradation of ox-LDL by HA-SMC (from 4019 +/- 529 ng/mg cell protein to 6207 +/- 287 ng/mg cell protein; P = .0033). AII also increased the expression of 12-lipoxygenase (12-LO) and 15-lipoxygenase (15-LO) by approximately 2.2-fold (P = .03) and approximately 3-fold (P = .006), respectively. In addition, AII (10(-7) mol/L) increased the release of 12- and 15-hydroxyeicosatetraenoic acid from VSMC within 10 min approximately 3-fold (P = .03) and 50% (P < .05), respectively. CONCLUSIONS: Our study findings provide evidence that angiotensin II upregulates LOX-1 and 12-LO and 15-LO expression in human VSMC, thereby potentially providing mechanisms for both accelerated LDL oxidation within the cell and the internalization of exogenous ox-LDL, two processes that could increase the susceptibility of human VSMC to further transformation into foam cells.