Arresten对人脐静脉内皮细胞增殖和凋亡影响的研究

目的:观察血管生成抑制因子Arrest-en对人脐静脉内皮细胞Huvec增殖和凋亡的影响.探讨VEGFR在其中的作用.方法:应用MTT法检测不同浓度的Arresten对Huvec细胞增殖的影响;流式细胞仪检测Arresten对Huvec细胞凋亡的影响;半定量RT-PCR和蛋白质印迹法分别检测VEGFR mRNA水平及VEGFR蛋白水平的表达.结果:MTT比色法显示,Arresten对Huvec细胞增殖具有抑制作用,随着浓度的增加,Arresten对Hhvec细胞增殖抑制作用也增强;但当浓度增加到800 ng/L后其增殖抑制率不再提高,而此浓度时Huvec细胞的凋亡率达到峰值的(59±0.3)%.经过Ar-resten处理.Huvec细胞的VEGFR mRNA表达及VEGFR蛋白表达均显著下降.结论:Airest-gn通过降低Huvec细胞的VEGFR表达而抑制Huvec细胞增殖并促进Huvec细胞凋亡,这可能是Arresten抑制血管生成的机制之一.     

TNP-470抑制小鼠恶性腹腔积液形成的实验研究

目的 :研究血管生成抑制剂TNP 4 70对小鼠恶性腹腔积液形成的抑制作用。方法 :将小鼠肝癌腹水型细胞系Hca F2 5接种于小鼠腹腔 (2× 10 5/鼠 )。将 10 0只小鼠随机分成对照组 (0 9%NS) ,化疗组 (DDP 1mg/kg) ,TNP 4 70低、中、高剂量组 (30mg/kg、6 0mg/kg、90mg/kg)。自第 2天起分别腹腔内给药 (0 2ml/鼠 ) ,隔日给药 ,共 7次。第 15天处死部分小鼠测各项指标 ,余小鼠观察生存期。结果 :化疗组 ,TNP 4 70低、中、高剂量组的腹水抑制率分别为 74 77% ,5 2 33%、80 11%和 92 89% ;腹膜瘤结节的形成率分别为 10 0 % ,70 %、80 %、5 0 %和 30 %。在生存时间上 ,各治疗组较对照组明显延长生存期 (P <0 0 5 )。结论 :TNP 4 70具有抑制小鼠恶性腹腔积液的形成和延长小鼠生存时间的作用。     

血管内皮生长因子在肝癌血管内皮细胞体外管腔形成中量效和时效局限性的实验研究

目的：利用体外管腔形成模型,研究血管内皮生长因子（VEGF）对肿瘤血管内皮细胞（TECs）调控的精准性,探讨以 VEGF 为靶点的抗肿瘤药物在临床应用中出现缺陷的潜在机制。方法采用 CD31免疫磁珠分选人肝癌标本中的 TECs,在含 Matrigel 基质胶的96孔板中,分别与不同浓度 VEGF 共培养,观察不同时间的 TECs 体外管腔形成能力,以正常人脐静脉血管内皮细胞（ HUVECs）为对照。结果1）体外分离培养的 TECs 拟血管内皮细胞梭状形态,其96％的细胞表达内皮细胞特异性标记 CD31;2）TECs 在微小量（基础培养条件,2 ng·mL -1）VEGF165时,体外管腔形成较少或不成腔,而对照组 HUVECs 却能形成明显的管腔并分支成网;当附加10 ng·mL -1 VEGF165时,在4 h 观察到 TECs 如同 HUVECs 形成了管腔,在6 h 出现明显的分支网;然而,当附加20 ng·mL -1 VEGF165时,在6 h 观察到 TECs 形成的管腔明显减少;统计分析显示,10 ng·mL -1 VEGF165组 TECs 成管能力比2 ng·mL -1 VEGF165组高出6倍（ P ﹤0.001）,而20 ng·mL -1 VEGF165组 TECs 成管能力显著下降至10 ng·mL -1 VEGF165组的4.5倍（P ﹤0.001）;3）10 ng·mL -1 VEGF165组在培养4、6、8 h 均可见 TECs 管腔形成,但以6 h 为显著;在20 h 时,TECs 的管腔消失,而对照组 HUVECs 却还有明显的管腔分支网。结论肝癌 TECs 体外管腔形成对 VEGF165既有依赖性但又有量-效局限性,过高 VEGF 浓度能抑制性影响 TECs（而不是 HUVECs）管腔形成能力。在 VEGF 的刺激下,TECs 体外管腔形成的时效性短于 HUVECs。我们的实验结果提示,临床应用抗 VEGF 的抗肿瘤药物疗效不一可能与 VEGF 在 TECs 体外管腔形成的量效和时效的局限性有关。     

血管生成抑制剂TNP-470抑制肝癌生长和转移的实验研究

目的　研究血管生成抑制剂TNP 470对肝细胞癌生长和转移的抑制作用。方法　把高转移人肝癌模型(LCI D2 0 )的肿瘤组织小块种植于裸鼠皮下 ,将 2 4只裸鼠随机分成对照组、治疗组。第 2天起分别给予溶剂 ( 3%酒精 )、TNP 470 ( 30mg kg)隔天皮下注射 ,共 8次。 结果　对照组、治疗组皮下瘤重分别为 ( 2 0 4± 0 34)g、( 0 98± 0 34) g(P<0 0 0 1) ;两组AFP分别为 ( 76 8 6± 2 82 3) μg L ,( 93 4±5 8 6 ) μg L (P <0 0 0 1) ,两组肺转移率分为5 0 % ( 6 12 )、8 3 % ( 1 12 ) (P <0 0 5 )。结论　血管生成抑制剂TNP 470能显著抑制肝细胞癌的生长和转移     

大肠癌组织血内皮生长因子表达与血管生成和细胞增殖关系的研究

目的：研究血管内皮生长因子（VEGF）在大肠癌组织中的表达及其与血管生成和细胞增殖的关系。方法：应用免疫组织化学方法检测98例大肠癌组织中VEGF表达及微血管密度（MVD）、PCNA标记指数（PCNA LI）,并分析VEGF与MVD、PCNA LI的相关性。结果：98例大肠癌中,VEGF表达阳性36例（３６．７％）;VEGF表达阳性的肿瘤其ＭＶＤ和ＰＣＮＡ ＬＩ显著高于VEGF阴性（Ｐ＜０．０５）。VEGF表达与ＭＶＤ、ＰＤＮＡ LI显示正相关（P＜0．05）。有转移组（有包淋结转移移和远处转移VEGF表达明显高于无转移,VEGF表达随肿瘤分期的升高而增高。结论：VEGF在大肠癌血管生成和细胞增殖中起重要作用。     

血管生成抑制剂TNP—470抑制Lewis肺癌生长和转移的实验研究

目的采用Ｌｅｗｉｓ肺癌来验证血管生成抑制剂ＴＮＰ－４７０对肿瘤生长和转移的抑制作用。方法将Ｌｅｗｉｓ肺癌细胞接种于Ｃ５７ＢＬ小鼠皮下（２．４×１０６／鼠）。将２０只小鼠随机分成对照组和治疗组,自第２天起分别给予溶剂（３％酒精）０．２ｍｌ和ＴＮＰ－４７０（４０ｍｇ／ｋｇ）,隔天给药１次,共８次。第２２天时,测定对照组和治疗组的皮下瘤重及肺转移率,分别进行ｔ检验和χ２检验。结果两组皮下瘤重分别为３．７７±１．０５ｇ和１．９８±０．９６ｇ（Ｐ＝０．０００９）;两组肺转移率分别为８０％和３０％（Ｐ＝０．０３）。结论血管生成抑制剂ＴＮＰ－４７０能明显抑制Ｌｅｗｉｓ肺癌的生长和转移。     

血管内皮抑制素抗肿瘤作用

血管内皮抑制素(endostatin)是继血管抑素(angiostatin)后发现的另一种特异性内源性血管生成抑制剂,能阻断促进肿瘤血管生长的多种途径,特异地抑制血管内皮细胞的增殖和迁移,从而抑种制肿瘤的生长和转移,又具有抗瘤谱广、毒性低和无获得性耐药性等优点,而且与多种治疗方法联合具有协同作用.     

Endostatin对结肠癌生长和转移抑制作用的实验研究

背景与目的:结肠癌的生长、转移是血管生成依赖性的,血管生成抑制剂有望通过抑制肿瘤血管生成,诱导结肠癌细胞凋亡,有效地抑制结直肠癌的生长和转移。肿瘤的抗血管生成治疗对选择手术时机和方式、制定综合治疗方案,提高结肠癌患者5年生存率都具有重要意义。本实验研究血管生成抑制因子Endostatin对结肠癌生长和转移的抑制作用,并探讨其对结肠癌细胞凋亡的影响。方法:采用人结肠腺癌细胞株SW1116完整组织块裸鼠原位种植,建立类似于临床的结肠癌转移裸鼠模型。种植后第1周开始皮下注射Endostatin,每天一次,剂量为0mg/kg(对照组)、5mg/kg、10mg/kg、20mg/kg(治疗组),共用6周。种植后第7周处死动物,测量原位肿瘤瘤重、抑瘤率、肿瘤微血管密度(intratumoralmicrovesseldensity,MVD)、肿瘤细胞凋亡指数(apoptoticindex,AI),观察肿瘤细胞腹膜、肝、其他脏器转移及腹水情况。结果:Endostatin剂量为0mg/kg、5mg/kg、10mg/kg、20mg/kg时,原位肿瘤瘤重分别为(1.31±0.36)g、(0.42±0.17)g、(0.21±0.09)g、(0.13±0.05)g;抑瘤率分别为0%、67.9%、84.0%、90.1%;MVD分别为(12.8±4.1)、(5.9±2.5)、(2.2±1.4)、(0.74±O.3);AI分别为(3.87±2.61)%、(6.89±5.18)%、(13.24±4.76)%、(20.97±9.04)%;腹膜转移率分别为9     

肿瘤新生血管生成抑制药物研究进展

新生血管生成抑制药物可以从不同途径阻断新生血管的生成,达到治疗肿瘤的目的.目前新牛血管生成抑制药物可分为阻断促血管生成因子作用通路的物、直接抑制内皮细胞药物、抑制基底膜降解的药物、抑制细胞整合素的药物、表皮生长因子受体抑制剂和其他种类,有较好的应用前景.     

小管形成实验在肿瘤微血管形成中的应用研究

肿瘤的增殖与侵袭有赖于肿瘤新生微血管的形成,破坏或者抑制此过程就能切断肿瘤生长的“营养与能源”,因此肿瘤血管生成抑制因子、抗血管生成的药物及研究方法已成为人们研究的热点。本文就小管形成实验在肿瘤微血管生成的应用及影响小管实验管腔形成的各项因素做一综述。     

PTEN抑制人脐静脉内皮细胞ECV304的增殖和VEGF的表达

目的:探讨与张力蛋白同源的10号染色体缺失的磷酸酶基因(phosphatase and tensin hemology deleted on chromo-some ten gene,PTEN)对人脐静脉内皮细胞ECV304细胞增殖、凋亡,及血管内皮生长因子(vascular endothelial growth factor,VEGF)及其受体1(VEGF receptor 1,VEGFR1)的影响。方法:将携带有野生型PTEN及绿色荧光蛋白(green fluorescent protein,GFP)基因的腺病毒Ad-PTEN-GFP及空载体腺病毒Ad-GFP感染ECV304细胞,MTT实验、Hoechst3342染色法及流式细胞术检测ECV304细胞的增殖和凋亡。实时荧光定量PCR法检测Ad-PTEN-GFP感染后ECV304细胞中PTEN、VEGF和VEG-FR1 mRNA表达水平,ELISA检测ECV304细胞培养上清中VEGF的水平。鸡胚尿囊膜(chick chorioallantoic membrane,CAM)血管生长实验检测PTEN对鸡胚血管生长的影响。结果:与Ad-GFP相比,Ad-PTEN-GFP感染能明显抑制ECV304细胞的增殖,诱导细胞凋亡,5 d时增殖抑制率可达(50.38±5.42)%、细胞凋亡率达(73.3±5.3)%。当感染复数为100时,Ad-PTEN-GFP组ECV304细胞的VEGF及VEGFR1 mRNA表达水平分别为未感染组的(13.40±1.32)%及(46.12±5.20)%。同时,Ad-PTEN-GFP感染能够明显抑制CAM体内血管生长[血管指数(57.6±3.37)%vs(92.2±4.37)%,P<0.05]。结论:PTEN能显著抑制人脐静脉内皮细胞ECV304的增殖、促进其凋亡,其机制可能与抑制VEGF和VEGFR1表达,抑制血管新生有关。     

瞬时转染Arresten基因对血管内皮细胞迁移的影响

目的研究瞬时转染Arresten基因对血管内皮细胞迁移的影响,并为后续动物实验探索最佳体内转染DNA-脂质体比例.方法以不同比例之质粒DNA-Lipofectamine 2000转染肝癌细胞系HepG-2细胞,瞬时转染经RT-PCR证实目的基因已转入细胞内48 h后收集上清,上清液与血管内皮细胞以划痕法共培养,计算迁移率.结果不同比例转染细胞的上清液均可抑制内皮细胞的迁移,以DNA-脂质体比例1:1,抑制率最高.结论瞬时转染Arresten基因可抑制血管内皮细胞的迁移,并为后续动物实验奠定一定的基础.     

Selective growth inhibition by sangivamycin of human umbilical vein endothelial cells

In the course of our screening for selective growth inhibitors of human umbilical vein endothelial cells (HUVECs), we isolated sangivamycin from the culture filtrate of Streptomyces. It inhibited the growth of HUVECs at approximately 30 times lower concentration than that needed to inhibit the growth of WI-38 human fibroblasts. Structurally-related nucleosides, such as toyocamycin, tubercidin, and formycins A and B, did not show the differential inhibition. Although sangivamycin is known to inhibit protein kinase C, other protein kinase C inhibitors did not inhibit the growth of HUVECs selectively. Sangivamycin effectively inhibited S-phase induction in HUVECs, like TNP-470 and LLnL, known selective inhibitors. However, unlike them sangivamycin did not induce p21 expression. On the other hand, sangivamycin was found to inhibit DNA synthesis selectively in HUVECs. Thus, sangivamycin was shown to be a new selective growth inhibitor of HUVECs acting on DNA synthesis.     

X射线照射对人脐静脉内皮细胞焦亡的影响

目的：探讨X射线照射对人脐静脉内皮细胞（HUVEC）焦亡的影响。方法：单次10 Gy X射线照射HUVEC细胞,采用ELISA法检测照射后0~72 h HUVEC分泌细胞因子IL-1β、IL-6、TNF-α和IL-18的浓度,Western blot法检测照射后6~48 h HUVEC内Caspase-1的活化水平,采用透射电子显微镜检测照射后72 h HUVEC形态的变化。采用流式细胞术检测单次10 Gy以及多次小剂量（2.5 Gy/d,连续4 d）照射后HUVEC焦亡率的变化。结果：10 Gy X射线照射后0~72 h HUVEC中IL-1β、IL-6、TNF-α和IL-18浓度与对照组（0 Gy组）相比均明显升高（P<0.05）。10 Gy X射线照射后6~48 h细胞内Caspase-1活化水平升高（P<0.05）,细胞呈现体积增大肿胀状态。单次10 Gy照射组和多次小剂量照射组细胞焦亡率均明显高于空白对照组（P<0.01）;此外,单次10 Gy照射组细胞焦亡率较多次小剂量照射组细胞升高约1倍（P<0.01）。结论：X射线照射可引起人脐静脉内皮细胞HUVEC焦亡;在总剂量相同情况下,单次大剂量照射引起的HUVEC焦亡水平明显高于多次小剂量照射。     

Radiosensitivity and sublethal damage repair in human umbilical cord vein endothelial cells

The assessment of the comparative radiosensitivity of different parenchymal cells is potentially of great importance in clinical radiotherapy. Previous studies from various laboratories using vessel regeneration techniques have demonstrated that endothelial cells are quite radioresistant, having a Do in excess of 250 rads. The present studies were undertaken to investigate the radiosensitivity of human endothelial cells obtained from umbilical cord veins (HEC) using "colony formation" as an endpoint, and to evaluate their ability to repair sublethal radiation damage (SLD). The endothelial origin of the cells in the surviving colonies was demonstrated by their positive staining for factor VIII antigen. The survival curve for HEC has a Do of about 165 rads, with a moderate initial shoulder. Dose fractionation studies demonstrate a moderate capability to repair SLD, comparable to other human cells studied including fibroblasts and other normal diploid cells in vitro. These studies indicate that HEC, being a terminally differentiated cell type with various differentiated markers, may prove useful in radiobiological and radiocarcinogenesis studies.     

阿魏酸对人脐静脉血管内皮细胞辐射损伤的保护作用及其机制

目的：研究阿魏酸对电离辐射所致人脐静脉血管内皮细胞（HUVEC）损伤的保护作用,及其对辐射敏感蛋白Thbd和γH2AX的影响,探讨阿魏酸的抗辐射作用与机制。方法：以4~16 Gy的⁶⁰Co γ射线照射HUVEC细胞,照后48 h以MTS法检测细胞活力,探索适宜照射剂量。以10 Gy γ射线照射HUVEC细胞,分别于照射后1、3、6、12、24和48 h提取细胞总蛋白,蛋白质印迹法检测蛋白Thbd和γH2AX的表达水平。并于照射前2 h,预防性给予细胞0.001~1 μmol/L的阿魏酸,照后48 h检测细胞活力、Thbd和γH2AX蛋白表达水平的改变。结果：与未照射组（0 Gy）比较,HUVEC受到10 Gy γ射线照射后48 h,细胞活力约降低30%（P < 0.05）。以此剂量照射,照后1 h Thbd约降至正常水平的0.6（P < 0.05）,照射后48 h γH2AX约升高至正常水平的5倍（P < 0.05）。与照射对照组比较,0.1和1 μmol/L 的阿魏酸作用后,受照HUVEC的细胞活力提高（P < 0.05）,Thbd蛋白表达升高（P < 0.05）,γH2AX蛋白表达降低（P < 0.05）。结论：0.1~1 μmol/L的阿魏酸可调节10 Gy γ射线照射后HUVEC的Thbd和γH2AX蛋白的表达水平,从而促进HUVEC增殖,提高其细胞活力,发挥抗辐射作用。     

Hyperthermia decreases cytokine-mediated adhesion molecule expression on human umbilical vein endothelial cells

Although hyperthermia has been used as an effective cancer treatment modality, its effects on metastasis of tumour cells are not clear. Since adhesion molecules play a key role in metastasis, we evaluated how the expression of adhesion molecules is influenced by hyperthermia. Human umbilical vein endothelial cells were incubated in vitro for 1 h. at 39, 42, 43 and 44°C with and without addition of tumour-necrosis factor (TNF) or interferon-gamma (IFN-γ) and the expression of endothelial cell leukocyte adhesion molecule-1 (ELAM-1), intercellular adhesion molecule-1 (ICAM-1) and major histocompatibility complex (MHC) class-II molecule was measured. Expression of MHC class-II molecules and expression of unstimulated constituent ICAM-1's was not reduced by heat treatment. In contrast, expression of cytokine-induced ELAM-1's and ICAM-1's was significantly lower after heat treatment. The adhesion to HUVEC in vitro of HL-60 leukemia cells, which express sialyl-Lewis-x antigen as a ligand to ELAM-1, was diminished after incubation at 42°C and totally lost after treatment at 44°C. This suggests that any decrease in metastasis formation after heat treatment, which is occasionally observed, could be due to a reduced action of TNF or related cytokines on adhesion molecule induction and subsequent membrane expression by the endothelial cell. A possible underlying mechanism involved is a heat-induced alteration or blockage of the biosynthetic pathways required for synthesis of ELAM-1 and ICAM-1 proteins.     

Anti-angiogenic effects of a nutrient mixture on human umbilical vein endothelial cells

Matrix metalloproteinases (MMPs) have been recognized as key players in the degradation of the extracellular matrix (ECM) by migration and proliferation of endothelial cells and their subsequent invasion of the underlying stroma. The prevention of ECM degradation through the inhibition of MMP activity has been shown to be a promising therapeutic approach to block the invasion that occurs during angiogenesis. In previous studies, we demonstrated the anti-tumor effect of a nutrient mixture (NM) containing ascorbic acid, lysine, proline, green tea extract, arginine, N-acetyl cysteine, selenium, copper and manganese on various tumor cell lines in vivo and in vitro. The aim of the present study was to determine whether this mixture has anti-angiogenic effects on human umbilical vein endothelial cells (HUVECs). At near confluence, the HUVEC cell cultures were tested with NM at 0, 10, 50, 100, 500, and 1000 microg/ml in triplicate at each dose for proliferation, migration, MMP expression, and invasion. Cell proliferation was evaluated by MTT assay, invasion potential by Matrigel invasion, MMP expression by gelatinase zymography, and cell migration by a 2 mm-wide scratch in plates. For tube formation, HUVECs were cultured in previously polymerized Matrigel. NM inhibited HUVEC migration, MMP expression and invasion through Matrigel in a dose-dependent manner. Zymography showed a dose-dependent inhibition of MMP-2 expression with virtual total inhibition at a 500 microg/ml concentration. Invasion through Matrigel was totally inhibited at 500 microg/ml NM. NM reduced cell migration by scratch test in a dose-dependent fashion with total inhibition at a 500 microg/ml concentration. NM also inhibited the tube formation of HUVECs, but did not significantly inhibit cell proliferation. These results together with our earlier findings suggest that NM is a relatively non-toxic formulation with anti-angiogenic effects, such as inhibiting vascular tube formation and endothelial cell invasion and migration.     

异鼠李素通过减轻氧化应激延缓D-半乳糖诱导的人脐静脉内皮细胞衰老

目的：探讨沙棘中的重要成分异鼠李素（ISO）对细胞衰老的影响及机制。方法：采用D-半乳糖（D-Gal）诱导细胞衰老模型,取20～23代的人脐静脉内皮细胞（HUVEC）分为4组：对照组、D-Gal组、D-Gal+ISO组（5 μmol/L）、D-Gal+ISO组（10 μmol/L）。其中D-Gal浓度为10 g/L,干预时间为72 h。采用CCK-8试剂盒检测各组细胞活力;衰老相关β-半乳糖苷酶（SA-β-Gal）染色试剂盒检测细胞衰老状态;各相关试剂盒检测细胞总活性氧（ROS）水平、丙二醛（MDA）含量、总超氧化物歧化酶（SOD）活性和过氧化氢酶（CAT）活性。Western blot法检测衰老标志蛋白p21、p27和核因子NF-E2相关因子2（Nrf2）及其下游蛋白表达水平。结果：ISO浓度≤10 μmol/L时对HUVEC无明显毒性作用;与对照组比较,D-Gal能够诱导细胞衰老指标SA-β-Gal活性增加（P<0.05）;提高p21、p27表达水平,提高细胞总ROS水平和MDA含量,降低总SOD和CAT活性,降低Nrf2及下游蛋白表达水平（P<0.05）。与D-Gal组比较,ISO能够降低细胞SA-β-Gal活性,抑制p21、p27表达,降低细胞总ROS水平和MDA含量,提高总SOD和CAT活性,增强Nrf2及下游蛋白表达（P<0.05）。结论：ISO可以通过减轻氧化应激,延缓D-Gal诱导的HUVEC细胞衰老,在此过程中激活Nrf2通路可能是其发挥抗衰老作用的重要机制。     

Far-infrared radiation inhibits proliferation,migration, and angiogenesis of human umbilical vein endothelial cells by suppressing secretory clusterin levels

Far-infrared (FIR) radiation is known to lessen the risk of angiogenesis-related diseases including cancer. Because deficiency of secretory clusterin (sCLU) has been reported to inhibit angiogenesis of endothelial cells (EC), we investigated using human umbilical vein EC (HUVEC) whether sCLU mediates the inhibitory effects of FIR radiation. Although FIR radiation ranging 3–25 μm wavelength at room temperature for 60 min did not alter EC viability, further incubation in the culture incubator (at 37 °C under 5% CO₂) after radiation significantly inhibited EC proliferation, in vitro migration, and tube formation in a time-dependent manner. Under these conditions, we found decreased sCLU mRNA and protein expression in HUVEC and decreased sCLU protein secreted in culture medium. Expectedly, the replacement of control culture medium with the FIR-irradiated conditioned medium significantly decreased wound closure and tube formation of HUVEC, and vice versa. Furthermore, neutralization of sCLU with anti-sCLU antibody also mimicked all observed inhibitory effects of FIR radiation. Moreover, treatment with recombinant human sCLU protein completely reversed the inhibitory effects of FIR radiation on EC migration and angiogenesis. Lastly, vascular endothelial growth factor also increased sCLU secretion in the culture medium, and wound closure and tube formation of HUVEC, which were significantly reduced by FIR radiation. Our results demonstrate a novel mechanism by which FIR radiation inhibits the proliferation, migration, and angiogenesis of HUVEC, via decreasing sCLU.