槲皮素对肺动脉平滑肌细胞酪氨酸磷酸化蛋白表达及大鼠低氧性肺动脉高压的影响

肺血管构型重建是慢性缺氧性肺动脉高压的病理学基础,主要表现为中膜平滑肌细胞增殖及迁移,而平滑肌细胞的增殖依赖于多种生长因子的作用,尤其是血小板衍生生长因子（ＰＤＧＦ）。我们通过酪氨酸蛋白激酶（ＴＰＫ）抑制剂槲皮素（Ｑｕｅｒｃｅｔｉｎ）来观察ＰＤＧＦ诱导的肺动脉平滑肌细胞（ＰＡＳＭＣ）酪氨酸磷酸化蛋白的表达及其对大鼠低氧性肺动脉高压的影响。材料与方法　（１）材料：ＰＤＧＦＢＢ,Ｑｕｅｒｃｅｔｉｎ,抗磷酸化酪氨酸（均购自美国Ｓｉｇｍａ公司）,ＡＳＭ６８Ｋ图象分析仪（德国Ｌｅｉｔｅ公司）;流式细胞仪…     

动脉粥样硬化斑块组织中血小板衍化生长因子基因表达的研究

本实验在用透射电子显微镜观察动脉粥样硬化（ＡＳ）家兔血管平滑肌细胞（ＶＳＭＣ）超微结构的基础上，又用组织原位杂交技术检测了血小板衍化生长因子（ＰＤＧＦ）基因在ＡＳ家兔主动脉壁表达水平及分布。结果表明，高脂饮食ＡＳ家兔主动脉内膜增厚，斑块内有大量增生的ＳＭＣ，以合成型为主，在ＡＳ斑块边缘区及新生斑块区ＳＭＣ内可见大量ＰＤＧＦ－ＡｍＲＮＡ表达阳性颗粒，未见ＰＤＧＦ－Ｂ基因表达阳性颗粒。正常对照组家兔动     

精氨酸加压素促血管平滑肌细胞增殖效应及其对IL－6分泌的影响

我们以培养的ＳＤ大鼠血管平滑肌细胞（ＶＳＭＣｓ）为模型，动态观察了精氨酸加压素（ＡＶＰ）对ＶＳＭＣｓ增殖作用和白细胞介素－６（ＩＬ－６）分泌功能的影响，亦对ＩＬ－６与ＶＳＭＣｓ增殖效应的关系进行了研究，旨在探讨ＡＶＰ和ＩＬ－６在高血压发病中的意义。结果表明：（１）ＡＶＰ对培养大鼠ＶＳＭＣｓ具有明显促增殖效应，随剂量增加和时间延长其作用加强；（２）ＶＳＭＣｓ可自身分泌ＩＬ－６，ＡＶＰ对其分泌有明显的抑制作用，且作用时间愈长，抑制作用愈显著；（３）ＩＬ－６作用于ＶＳＭＣｓ可明显促进其ＤＮＡ合成。上述结果提示，ＡＶＰ与ＩＬ－６可能均参与了高血压的发病。     

莲心碱对自发性高血压大鼠血管平滑肌细胞增殖及对PDGF—B,bFGF,c …

用［＾３Ｈ］胸腺嘧啶核苷（［＾３Ｈ］ＴｄＲ）掺入法、电镜、免疫组化和原位杂交方法，在自发性高血压大鼠（ＳＨＲ）观察了莲心碱（Ｌｉｌｅｎ）对血管平滑肌细胞（ＶＳＭＣ）增殖的作用及对生长因子ＰＤＧＦ－Ｂ、ｂＦＧＦ及其相关癌基因ｃ－ｓｉｓ和ｃ－ｍｙｃ表达的影响。结果发现Ｌｉｅｎ在降低ＳＨＲ血压同时，能减少ＶＳＭＣ的线粒体，粗面内质网和［＾３Ｈ］ＴｄＲ掺入量，并能逆转ＶＳＭＣ增殖对ＰＤＧＦ０Ｂ、ｂＦＧＦ抗     

巨噬细胞集落刺激因子与血管平滑肌细胞增殖

目的一些以血管平滑肌细胞（ＶＳＭＣ）增殖为特点的血管疾病，在病变部位常有巨噬细胞浸润。本研究巨噬细胞集落刺激因子（ＭＣＳＦ）在ＶＳＭＣ生长调节中的作用。方法实验采用培养大鼠主动脉ＶＳＭＣ，细胞增殖观察指标采用氚标胸腺嘧啶核苷掺入法，并用Ｎｏｒｔｈｅｒｎｂｌｏｔ技术测定原癌基因表达。结果（１）Ｌ９２９细胞上清液（富含ＭＣＳＦ）及重组ＭＣＳＦ以剂量依赖关系刺激氚标胸腺嘧啶核苷掺入；（２）ＶＳＭＣ在接受刺激后表达某些原癌基因，如ｃｆｏｓ、ｃｍｙｃ、ｅｒｇ１和ＪｕｎＢ；（３）凝血酶、ＰＤＧＦ、ｂＦＧＦ与ＭＣＳＦ在促增殖作用上具有协同作用。结论ＭＣＳＦ与其它生长因子协同作用，通过自分泌／旁分泌机制调控ＶＳＭＣ增殖，从而可能在血管病变的形成和进展中起重要作用     

缺氧性血管收缩反应时血浆MDA和RBC中SOD的变化及绞股蓝总皂甙的影响

本文研究缺氧性肺血管收缩反应（ＨＰＶ）时狗血浆丙二醛（ＭＤＡ）含量和红细胞超氧化物歧化酶（ＳＯＤ）的变化及绞股蓝总皂甙（ＧＰ）的影响．吸入１０％Ｏ２５ｍｉｎ狗肺动脉压明显升高，此时血浆ＭＤＡ有升高趋势，但差异无统计学意义．缺氧前后ＲＢＣ中ＳＯＤ活力无明显变化．静注ＧＰ（２０ｍｇ／ｋｇ体重）后２５ｍｉｎ血浆ＭＤＡ显著降低，但不影响ＲＢＣ中ＳＯＤ活力．结果提示，ＧＰ有抗氧化作用，但氧自由基可能与狗急性ＨＰＶ的发生无明显关系．     

血小板衍生生长因子与缺氧性肺动脉高压

缺氧刺激血管内皮细胞产生释放血小板衍生生长因子（ＰＤＧＦ），ＰＤＧＦ与肺血管收缩、血管平滑肌细胞分裂增殖有密切关系。本就ＰＤＧＦ一般生物学特性、受体结构及在缺氧性肺动脉高压形成中的机制作一综述。     

精氨酸加压素促血管平滑肌细胞增殖效应及其对IL—6分泌的…

我们以培养的ＳＤ大鼠血管平滑肌细胞（ＶＳＭＣｓ）为模型，动态观察了精氨酸加压素（ＡＶＰ）对ＶＳＭＣｓ增殖作用和白细胞介素－６（ＩＬ－６）分泌功能的影响，亦对ＩＬ－６与ＶＳＭＣｓ增殖效应的关系进行了研究，旨在探讨ＡＶＰ和ＩＬ－６在高血压发病中的意义。结果表明：（１）ＡＶＰ对培养大鼠ＶＳＭＣｓ具有明显保增殖效应，随剂量增加和时间延长其作用加强；（２）ＶＳＭＣｓ可自身分泌ＩＬ－６ＡＶＰ对其分泌有明显的抑     

反义c—myc寡核苷酸对AVP诱导鼠血管平滑肌细胞增殖的抑制作用

目的：探讨ＡＶＰ对鼠血管平滑肌细胞（ＶＳＭＣ）增殖的影响和反义ｃ－ｍｙｃ寡核苷酸对ＡＶＰ作用的干预效应。方法：以培养ＳＤ大鼠ＶＳＭＣ为模型,采用培养细胞计数,蛋白质定量和细胞周期分析方法及ｍＲＮＡ打点杂交技术,动蛋白质定量和细胞周期分析方法及ｍＲＮＡ打点杂交技术,动态观察ＡＶＰ对ＶＳＭＣ增殖的影响和反义ｃ－ｍｙｃ寡核苷酸的干预效果。结果：（１）ＡＶＰ促ＶＳＭＣ数目增加,在４８ｈ时与对照组比较,有统     

转染血管紧张素Ⅱ受体（AT1）反义核苷酸对血管平滑肌细胞增殖的 …

目的：评价转染ＡＴ１我核菩酸（ＡＴ１Ａ）对血管平滑肌细胞（ＶＳＭＣｓ）血管紧张Ⅱ（ＡｎｇⅡ）受体亚型ｍＲＮＡ表达、蛋白激酶Ｃ（ＰＫＣ）、丝裂素活化蛋白激酶Ｐ＾３８（Ｐ＾３８ＭＡＰＫ）蛋白表达,及蛋白核酸合成的作用。方法：ＲＴ－ＰＣＲ克隆ＡＴ１ ｃＤＮＡ序列（４７６ｂｐ）,将克隆的ＡＴ１ ｃＤＮＡ反向插入ＰｃＤＮＡ３．１,构建一完整的含ＡＴ１Ａ的质粒（ＰＡＴ１Ａ）,测序鉴定。转染培养的大鼠ＶＳＭＣｓ     

Effects of tetrandrine on growth factor-induced DNA synthesis and proliferative response of rat pulmonary artery smooth muscle cells

The objective of the present study was to investigate the effect of tetrandrine (a plant alkaloid isolated from Stephenia tetrandra) on growth factor-induced DNA synthesis and proliferative responses of rat pulmonary artery smooth muscle cells. Male rat and bovine pulmonary artery smooth muscle cells (PASMC) were cultured in Medium 199 containing FBS (10%). DNA synthesis was monitored from [(3)H]-thymidine uptake and cell proliferation by direct cell counting. In the present study FBS (1% v/v) caused a small increase in DNA synthesis above basal levels in rat and bovine PASMC (6% and 11% respectively). Platelet-derived growth factor (PDGF, 50 ng/ml), fibroblast growth factor (FGF, 50 ng/ml) or interleukin-1alpha (IL-1alpha, 100 pg/ml) alone increased rat PASMC proliferation (69-85%) and DNA synthesis above basal levels (76-92%). The addition of these growth factors in combination with FBS (1%) resulted in higher increases in DNA synthesis above basal levels (rat PASMC:PDGF, 465%; FGF, 421%; IL-1alpha, 406%; bovine PASMC:PDGF, 279%). Tetrandrine (10(-5) M) inhibited FBS (10%)-induced rat PASMC proliferation (90.5%) and DNA synthesis (89.0%). Tetrandrine significantly inhibited cell proliferation (86.5-98.5%) and DNA synthesis (79.9-89.0%) induced by FBS (1%) in combination with one of the following mitogens; PDGF (50 ng/ml), FGF (50 ng/ml), IL-1alpha (100 pg/ml). The inhibitory effects of tetrandrine were observed between 10(-6) and 10(-5)M and PASMC viability was not affected by tetrandrine below 3x10(-5) m. In summary, these results suggest that tetrandrine can exert anti-proliferative effects against a range of mitogenic stimuli for vascular smooth muscle cells in vitro. Such effects may contribute to the inhibitory effect of tetrandrine on pulmonary vascular remodelling associated with pulmonary hypertension.     

Regulation of iodothyronine deiodinase and roles of thyroid hormones in human coronary artery smooth muscle cells

Thyroid hormones have been reported to have significant effects on the peripheral vascular system, including relaxation of vascular smooth muscle cells and prevention of atherosclerosis. To exert its biological activity, thyroxine (T4) needs to be converted to 3,5,3'-triiodothyronine (T3) by type 1 and type 2 iodothyronine deiodinases. We have previously identified type 2 iodothyronine deiodinase (D2) expression in cultured human coronary artery smooth muscle cells (hCASMCs). In the present study, we have characterized the regulation of D2 expression in hCASMCs by stable prostacyclin analogue beraprost sodium (BPS) and platelet derived growth factor (PDGF), and the roles of thyroid hormones in the functions of hCASMCs. BPS increased D2 expression, whereas PDGF suppressed BPS stimulated D2 expression without affecting cAMP production in hCASMCs. PDGF increased DNA synthesis, while BPS, T3 or T4 suppressed PDGF stimulated DNA synthesis in hCASMCs. Inhibition of D2 activity by 3,3',5'-triiodothyronine (rT3) partially restored T4 suppression of PDGF stimulated DNA synthesis in hCASMCs. PDGF increased migration activity, whereas BPS, T3 or T4 suppressed PDGF stimulated migration activity of hCASMCs. These results suggest that D2 expression is increased by BPS and suppressed by PDGF in hCASMCs, and that intracellular thyroid hormone activation may be involved in the suppression of DNA synthesis and migration activity of hCASMCs.     

丝氨酸—苏氨酸蛋白激酶2蛋白表达在低氧致大鼠肺动脉平滑肌细胞增殖中的作用

目的通过观察低氧致大鼠肺动脉平滑肌细胞丝氨酸/苏氨酸蛋白激酶2蛋白表达水平变化与低氧致肺动脉平滑肌细胞增殖的关系,探讨丝氨酸/苏氨酸蛋白激酶2在低氧肺血管重建中的调控作用。方法组织块法培养肺动脉平滑肌细胞,采用蛋白印迹技术检测蛋白表达水平,采用甲基噻唑基四唑法、氚—胸腺嘧啶核苷掺入法检测肺动脉平滑肌细胞增殖。结果低氧刺激肺动脉平滑肌细胞不断增殖,常氧下氚—胸腺嘧啶核苷掺入检测值为0.372±0.059,随着低氧处理时间的延长氚—胸腺嘧啶核苷掺入检测值不断升高,其中低氧12 h达到0.703±0.100,与常氧组比较差异显著;常氧下甲基噻唑基四唑检测值为8374.39±545.31,随着低氧处理时间的延长,甲基噻唑基四唑检测值不断升高,低氧24 h达到11208.35±678.82,与常氧组比较差异显著。各组均检测出丝氨酸/苏氨酸蛋白激酶2蛋白的表达,图像定量分析显示各组蛋白表达与细胞增殖改变密切相关。结论丝氨酸/苏氨酸蛋白激酶2信号通路可能在低氧肺动脉高压中调节肺动脉平滑肌细胞增殖。     

慢性缺氧改变肺内动脉平滑肌细胞环氧合酶基因的表达

目的研究慢性缺氧对肺动脉平滑肌细胞环氧合酶基因表达的影响.方法根据常氧(PaO2152mmHg)及慢性缺氧(PaO240±5nmHg)的不同培养条件,将平滑肌细胞分为常氧组和慢性缺氧组,采用半定量RT-PCR技术检测大鼠肺内动脉平滑肌细胞环氧合酶(COX)基因的表达及其对急性缺氧刺激的反应.结果COX-1mRNA的表达不受缺氧及传代的影响,而COX-2mRNA的表达随慢性缺氧时间延长而增加,在4、6代慢性缺氧培养组均高于同代常氧组水平(P＜0.05).急性缺氧后COX-2mRNA增加的幅度在慢性缺氧组均大于同代常氧组,以第四代最为显著.结论慢性缺氧可增强急性缺氧时肺内动脉平滑肌细胞COX-2基因的表达,在慢性缺氧所致肺血管对缺氧的反应性降低中可能起作用.     

Antiproliferative effect of sildenafil on human pulmonary artery smooth muscle cells

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and by obstructive changes of the pulmonary vasculature including smooth muscle cell proliferation which leads to medial hypertrophy and subsequent luminal narrowing. Sildenafil, an orally active inhibitor of cGMP phosphodiesterase–type–5, exerts pulmonary vasodilator activity in PAH patients. We evaluated the effects of sildenafil on growth of cultured human pulmonary artery smooth muscle cells (PASMC). The results indicate that sildenafil reduced DNA synthesis stimulated by PDGF and dose dependently inhibited PASMC proliferation. These effects were paralleled by a progressive increase in cGMP content, followed by an accumulation of cAMP. The treatment with 8–bromo–cGMP or dibutyryl–cAMP mimicked all the effects of sildenafil. On the other hand, treatment of PASMC with inhibitors of cGMP–dependent protein kinase (PKG) or cAMP–dependent protein kinase (PKA) reversed the antiproliferative effect of sildenafil. In addition, sildenafil inhibited the phosphorylation of ERK, a converging point for several pathways leading to cell proliferation. This effect was partially reduced by PKG inhibition and completely abolished by PKA inhibition.We conclude that sildenafil exerts an antiproliferative effect on human PASMC that is mediated by an interaction between the cGMP–PKG and the cAMP–PKA activated pathways, leading to inhibition of PDGF–mediated activation of the ERK.     

BMP-2 gene expression and effects on human vascular smooth muscle cells

Bone morphogenetic proteins (BMPs) and their serine/threonine kinase receptors have been identified in atherosclerotic arteries and vascular smooth muscle cells, respectively. Thus, BMPs (the largest subfamily of the TGF-beta superfamily) have been implicated in the pathogenesis of atherosclerosis. However, the origins of BMP biosynthesis and the functional roles of BMP in blood vessels are unclear. The present study explored BMP-2 gene expression in various human blood vessels and vascular cell types. Functional in vitro studies were also performed to determine the effects of recombinant human BMP-2 on migration (transwell assay) and proliferation ([3H]-thymidine incorporation) of human aortic vascular smooth muscle cells (HASMC). RT-PCR experiments revealed BMP-2 gene expression in normal and atherosclerotic human arteries as well as cultured human aortic and coronary vascular smooth muscle cells, human umbilical vein endothelial cells (HUVECs) and human macrophages. In cellular migration studies, incubation with BMP-2 produced efficacious (相似文献   

L-精氨酸对低氧性肺动脉高压大鼠肺动脉平滑肌细胞凋亡的影响

目的 探讨L-精氨酸(L-Arg)对低氧性肺动脉高压大鼠不同节段肺动脉平滑肌细胞凋亡的影响。方法 将Wistar大鼠(n=19)随机分为对照组(n=7)、低氧组(n=6)及低氧 L-Arg组(n=6)。经右心导管法测定各组大鼠肺动脉压力和右室(RV)/左室 室间隔(LV S)比值,以分光光度法间接测定血浆一氧化氮(NO)含量,通过TUNEL法检测各组大鼠不同节段的肺动脉平滑肌细胞凋亡数目,并计算肺动脉平滑肌细胞凋亡数目与肺动脉平滑肌细胞数目比值。结果 低氧组大鼠肺动脉平均压(PAMP)显著高于对照组[(2.71±0.29)kPa vs(2.05±0.14)kPa,P<0.01],低氧 L-Arg组大鼠的PAMP显著低于低氧组[(2.23±0.18)kPa vs(2.71±0.29)kPa,P<0.05];低氧组大鼠RV/(LV S)比值显著高于对照组[(0.42±0.03)kPa vs(0.30±0.05)kPa,P<0.01],低氧 L-Arg组大鼠RV/(LV S)比值显著低于低氧组[(0.36±0.02)kPa vs(0.42±0.03)kPa,P<0.01];低氧组大鼠血浆NO含量明显低于对照组[(3.54±0.47)μmol/L vs(4.79±0.17)μmol/L,P<0.05],低氧 L-Arg组大鼠血浆NO含量显著高于低氧组[(5.21±0.26)μmol/L vs(3.54±0.47)μmol/L,P<0.01];低氧组大鼠与终末细支气管伴行的肺动脉和与呼吸细支气管伴行的肺动脉平滑肌细胞凋亡数目与平滑肌细胞数目比值明显低于对照组[(0.051±0.016     

Key role of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in pulmonary vascular remodeling and vascular angiogenesis associated with hypoxic pulmonary hypertension

We have found that 15-hydroxyeicosatetraenoic acid (15-HETE) induced by hypoxia was an important mediator in the regulation of hypoxic pulmonary hypertension, including the pulmonary vasoconstriction and remodeling. However, the underlying mechanisms of the remodeling induced by 15-HETE are poorly understood. In this study, we performed immunohistochemistry, pulmonary artery endothelial cells migration and tube formation, pulmonary artery smooth muscle cells bromodeoxyuridine incorporation, and cell cycle analysis to determine the role of 15-HETE in hypoxia-induced pulmonary vascular remodeling. We found that hypoxia induced pulmonary vascular medial hypertrophy and intimal endothelial cells migration and angiogenesis, which were mediated by 15-HETE. Moreover, 15-HETE regulated the cell cycle progression and made more smooth muscle cells from the G(0)/G(1) phase to the G(2)/M+S phase and enhanced the microtubule formation in cell nucleus. In addition, we found that the Rho-kinase pathway was involved in 15-HETE-induced endothelial cells tube formation and migration and smooth muscle cell proliferation. Together, these results show that 15-HETE mediates hypoxia-induced pulmonary vascular remodeling and stimulates angiogenesis via the Rho-kinase pathway.     

Intermedin modulates hypoxic pulmonary vascular remodeling by inhibiting pulmonary artery smooth muscle cell proliferation

BackgroundHypoxic pulmonary arterial hypertension (PAH) is a disabling disease with limited treatment options. Hypoxic pulmonary vascular remodeling is a major cause of hypoxic PAH. Pharmacological agents that can inhibit the remodeling process may have great therapeutic value.ObjectiveTo examine the effect of intermedin (IMD), a new calcitonin gene-related peptide family of peptide, on hypoxic pulmonary vascular remodeling.MethodsRats were exposed to normoxia or hypoxia (∼10% O₂), or exposed to hypoxia and treated with IMD, administered by an implanted mini-osmotic pump (6.5 μg/rat/day), for 4 weeks. The effects of IMD infusion on the development of hypoxic PAH and right ventricle (RV) hypertrophy, on pulmonary vascular remodeling, on pulmonary artery smooth muscle cell (PASMC) proliferation and apoptosis, and on the activations of l-arginine nitric oxide (NO) pathway and endoplasmic reticulum stress apoptotic pathway were examined.ResultsRats exposed to hypoxia developed PAH and RV hypertrophy. IMD treatment alleviated PAH and prevented RV hypertrophy. IMD inhibited hypoxic pulmonary vascular remodeling as indicated by reduced wall thickness and increased lumen diameter of pulmonary arterioles, and decreased muscularization of distal pulmonary vasculature in hypoxia-exposed rats. IMD treatment inhibited PASMC proliferation and promoted PASMC apoptosis. IMD treatment increased tissue level of constitutive NO synthase activity and tissue NO content in lungs, and enhanced l-arginine uptake into pulmonary vascular tissues. IMD treatment increased cellular levels of glucose-regulated protein (GRP) 78 and GRP94, two major markers of endoplasmic reticulum (ER) stress, and increased caspase-12 expression, the ER stress-specific caspase, in lungs and cultured PASMCs.ConclusionsThese results demonstrate that IMD treatment attenuates hypoxic pulmonary vascular remodeling, and thereby hypoxic PAH mainly by inhibiting PASMC proliferation. Promotion of PASMC apoptosis may also contribute to the inhibitory effect of IMD. Activations l-arginine–NO pathway and of ER stress-specific apoptosis pathway could be the mechanisms mediating the anti-proliferative and pro-apoptotic effects of IMD.     

Novel Nox inhibitor VAS2870 attenuates PDGF-dependent smooth muscle cell chemotaxis, but not proliferation

OBJECTIVE: Reactive oxygen species (ROS) produced by NAD(P)H oxidases (Nox) play a significant role in the pathophysiology of cardiovascular diseases. Expression and activity of NAD(P)H oxidases are regulated by growth factors such as angiotensin II and platelet-derived growth factor (PDGF). We characterized the effects of the novel Nox inhibitor VAS2870 on PDGF-dependent ROS liberation and cellular events in vascular smooth muscle cells (VSMC). METHODS AND RESULTS: PDGF-BB increased NAD(P)H oxidase activity (lucigenin-enhanced chemiluminescence) and intracellular ROS levels (detected by confocal laserscanning microscopy using 2,7-DCF) to 229+/-9% and 362+/-54% at 1 and 2 h, respectively. Preincubation with VAS2870 (10 and 20 microM) completely abolished PDGF-mediated NAD(P)H oxidase activation and ROS production. Since ROS are involved in various growth factor-induced cellular functions, the influence of VAS2870 on PDGF-induced DNA synthesis and chemotaxis was determined. PDGF promoted a 4.2+/-0.2-fold increase of VSMC migration (modified Boyden chamber, p<0.01) and increased DNA synthesis by maximally 3.2+/-0.4-fold (BrdU incorporation, p<0.01) in a concentration-dependent manner. Preincubation with VAS2870 (0.1-20 microM) did not affect PDGF-induced cell cycle progression. However, it abolished PDGF-dependent chemotaxis of VSMC in a concentration-dependent manner (100% inhibition at 10 microM). These findings were related to PDGF-dependent signaling events. Western blot analyses using phospho-specific antibodies revealed that the downstream signaling molecules Akt, Erk, and Src were activated by PDGF. However, VAS2870 blocked PDGF-dependent activation of Src, but not of Akt and Erk, in a concentration-dependent manner. CONCLUSIONS: VAS2870 effectively suppresses growth factor-mediated ROS liberation in VSMC. Furthermore, it completely inhibits PDGF-dependent VSMC migration, whereas it does not affect DNA synthesis. These divergent effects reflect the critical role of Src activity, which-in contrast to Akt and Erk-appears to be redox-sensitive and is absolutely required for PDGF-induced chemotaxis, but not cell cycle progression.