血小板源生长因子对大鼠血管平滑肌细胞表达血管细胞粘附分子1的影响

目的本实验研究血小板源生长因子对血管平滑肌细胞表达血管细胞粘附分子1的影响以及对血管平滑肌细胞与单核细胞粘附的作用。方法利用基因芯片和RT-PCR技术检测鼠主动脉血管平滑肌细胞经血小板源生长因子处理0min、20min、6h后血管平滑肌细胞表达血管细胞粘附分子1的mRNA表达变化;细胞粘附实验观察血管平滑肌细胞经血小板源生长因子分别处理0min、20min、6h后与单核细胞粘附情况。结果血小板源生长因子对鼠血管平滑肌细胞表达血管细胞粘附分子1的表达有显著的诱导作用,其诱导作用在20min即已出现(P<0.05),6h时明显增强(P<0.01)。细胞粘附实验显示随着血小板源生长因子的作用时间的延长,血管平滑肌细胞与单核细胞的粘附率增高,血小板源生长因子处理20min和6h后粘附率是对照组的1.92倍和3.04倍(P<0.05)。结论血小板源生长因子明显诱导血管平滑肌细胞中血管平滑肌细胞表达血管细胞粘附分子1的表达,促进血管平滑肌细胞与单核细胞的粘附,从而参与了损伤早期,白细胞向内膜下迁移的炎症反应。     

洛伐他汀对血管平滑肌细胞基质金属蛋白酶3表达的影响

观察洛伐他汀对免血管平滑肌细胞基质金属蛋白酶3表达的影响及其作用机制。用Westem blot检测基质金属蛋白酶3蛋白水平，采用电泳迁移率变动分析法测定AP-1结合活性，用逆转录聚合酶链反应检测基质金属蛋白酶3mRNA水平。结果发现，自细胞介素1α和血小板源生长因子BB联合作用于免血管平滑肌细胞。可明显增加基质金属蛋白酶3的表达，洛伐他汀抑制这种刺激作用，使基质金属蛋白酶3的表达减低，且呈浓度依赖性；该抑制作用可被甲羟戊酸和双香叶酯基焦磷酸盐所逆转，而不被角鲨烯所逆转。白细胞介素1α和血小板源生长因子BB联合作用后使兔血管平滑肌细胞胆1结合活性和基质金属蛋白酶3mRNA水平明显增高，洛伐他汀抑制白细胞介素1α和血小板源生长因子BB上调AP-1结合活性的作用，但对基质金属蛋白酶3mRNA水平无明显影响。结果提示，洛伐他汀不依赖其调脂作用抑制血管平滑肌细胞基质金属蛋白酶3的生成，从而在理论上有抗动脉粥样硬化和增加斑块稳定性的作用。     

大鼠脑出血后血管内皮生长因子和基质金属蛋白酶9的表达及七叶皂苷钠的影响

目的探讨血管内皮生长因子和基质金属蛋白酶9在脑出血后的作用及七叶皂苷钠的影响。方法85只大鼠随机分为脑出血模型组(20)、治疗组A(20)、治疗组B(20)、假手术组(20)和正常对照组(5),采用胶原酶复制大鼠基底节区脑内血肿模型,通过免疫组织化学动态测定不同时间点(6 h、24 h、48 h和96 h)鼠脑内血肿周围脑组织中血管内皮生长因子和基质金属蛋白酶9的表达;并同时检测七叶皂苷钠干预后两者在相应时间点的动态变化。结果血管内皮生长因子和基质金属蛋白酶9在脑出血模型组出血后6 h表达明显增加,分别为12.67±1.50和9.27±1.28,24~96 h显著增加且均处于高峰(P<0.01);在出血后6~96 h两者的表达呈正相关,相关系数为0.479(P<0.01)。在七叶皂苷钠治疗组血管内皮生长因子、基质金属蛋白酶9的表达量明显受到抑制(特别是治疗B组抑制效果更明显),量效关系呈负相关其决定系数分别为0.107和0.083。结论1.脑出血后血管内皮生长因子的表达水平提高可能有协同诱导基质金属蛋白酶9的表达作用。2.七叶皂苷钠可能通过抑制基质金属蛋白酶9和血管内皮生长因子的相关途径发挥抗脑水肿作用。     

E1A激活基因阻遏子蛋白与细胞膜受体IGF2R（11～13）结构域作用抑制人血管平滑肌细胞迁移

目的 研究人E1A激活基因阻遏子基因(CREG)蛋白在人血管平滑肌细胞迁移中的作用.方法 构建含有myc和His标签的野生型CREG(wtCREG)和去糖基化突变型CREG(mCREG)真核表达载体pcDNA3.1myc-His/wt/mCREG.转染人293F细胞株,Ni-NTA亲合层析方法纯化获得wtCREG和mCREG蛋白;将重组wtCREG(400 nmol/L)及mCREG蛋白(400 nmol/L),分别加入体外培养的低表达CREG的人血管平滑肌细胞OB2中,应用Western blot、细胞刮伤实验、明胶酶电泳方法观察两种重组人CREG蛋白对人血管平滑肌细胞迁移和分化等生物学行为的影响;通过不同浓度(2、4、8 mg/L)的胰岛素生长因子2受体(M6P/IGF2R)中和抗体与人M6P/IGF2R细胞外结构域蛋白小肽分别进行阻断实验,分析M6P/IGF2R是否参与介导CREG蛋白对平滑肌细胞迁移的调控.结果 刮伤实验发现,加入最佳效应浓度的wtCREG和mCREG蛋白24h后,OB2组细胞的迁移能力均明显下降;明胶酶电泳和Western blot检测结果也证实,两种重组CREG蛋白均可以使细胞外基质金属蛋白酶2、基质金属蛋白酶9的合成及活性减少,而组织金属蛋白酶抑制物表达则明显增加;同时,Western blot分析也证实,平滑肌细胞分化标志蛋白myocardin、SM α-actin、肌球蛋白重链和caldesmin表达增加,LM-1和FN表达减少.提示两种重组CREG蛋白均能够抑制体外培养的人血管平滑肌细胞迁移,促进其分化.IGF2R中和抗体和IGF2R小肽阻断实验证实:不同浓度的Anti-M6P/IGF2R能有效阻断两种CREG蛋白对人血管平滑肌细胞迁移和细胞外基质合成的调控作用.并且,M6P/IGF2R的第11 ～13结构域小肽片段对wt/mCREG蛋白的生物学效应也有明显的阻断作用.结论 重组CREG蛋白可能通过细胞膜表面M6P/IGF2R的11 ～13结构域抑制人血管平滑肌细胞迁移和细胞外基质分泌,维持细胞分化.     

凝血酶对大鼠血管平滑肌细胞血小板源性生长因子基因表达的影响

为了研究凝血酶对血管平滑肌细胞血小板源性生长因子基因表达的影响 ,探讨凝血酶刺激血管平滑肌细胞增殖的机制 ,通过培养SD大鼠胸主动脉血管平滑肌细胞 ,以3 H -TdR掺入率作为评价凝血酶促血管平滑肌细胞增殖的指标 ;用反转录聚合酶链反应检测凝血酶对血管平滑肌细胞血小板源性生长因子A链mRNA表达的影响 ;用Dotblot检测凝血酶对血管平滑肌细胞血小板源性生长因子B链mRNA表达的影响。结果表明 ,凝血酶促血管平滑肌细胞增殖呈浓度依赖性和时间依赖性 ,血管平滑肌细胞在基础状态下可检测到血小板源性生长因子A和B链mRNA表达 ,凝血酶刺激血管平滑肌细胞后 2h血小板源性生长因子A链mRNA表达开始增加 ,4～ 6h达高峰 ,持续 12h ,2 4～ 48h恢复正常。提示凝血酶对血管平滑肌细胞具有较强的促增殖作用 ,凝血酶促血管平滑肌细胞的增殖作用部分可能是通过诱导血管平滑肌细胞血小板源性生长因子A链mRNA的表达来实现的。     

同型半胱氨酸对大鼠血管平滑肌细胞基质金属蛋白酶2表达的影响

目的观察同型半胱氨酸对大鼠血管平滑肌细胞基质金属蛋白酶2表达的影响,探讨其致动脉粥样硬化可能的机制。方法体外培养大鼠主动脉平滑肌细胞,加入不同浓度的同型半胱氨酸分别作用24、48和72 h,采用免疫印迹法和明胶酶谱分析法检测细胞培养基中基质金属蛋白酶2的表达。结果同型半胱氨酸浓度在0.5~1.0 mmol/L时促进血管平滑肌细胞基质金属蛋白酶2的表达;浓度在5.0 mmol/L以上时抑制血管平滑肌细胞基质金属蛋白酶2的表达。同一浓度同型半胱氨酸作用72 h明显强于24 h和48 h。结论同型半胱氨酸可影响血管平滑肌细胞基质金属蛋白酶2的表达,在动脉粥样硬化中可能起着一定的促进作用。     

凝血酶对大鼠血管平滑肌细胞血小板源生长因子受体基因表达的影响

为了研究凝血酶对血管平滑肌细胞血小板源生长因子受体基因表达的影响 ,探讨凝血酶刺激血管平滑肌细胞增殖的机制 ,通过培养SD大鼠胸主动脉血管平滑肌细胞 ,用斑点杂交检测凝血酶对血管平滑肌细胞血小板源生长因子受体mRNA的表达。结果发现培养的血管平滑肌细胞在基础状态下可表达血小板源生长因子α受体和 β受体mRNA ,凝血酶在作用于血管平滑肌细胞 2～ 12h抑制了血管平滑肌细胞血小板源生长因子α受体 β受体mRNA的表达 ,2 4～ 48h后血管平滑肌细胞血小板源生长因子α受体 β受体mRNA的表达恢复到基础状态。提示凝血酶对血管平滑肌细胞具有较强的促增殖作用 ;凝血酶显著降低了血管平滑肌细胞血小板源生长因子α受体 β受体mRNA的表达     

白细胞介素-1β和肿瘤坏死因子-α对血管平滑肌细胞及基质金属蛋白酶-2骨桥蛋白基因表达的影响

促炎细胞因子白细胞介素－ １β和肿瘤坏死因子－ α是血管平滑肌细胞的强效促分裂原,为了探讨其促血管平滑肌细胞增殖是否与细胞外基质降解及粘附蛋白合成有关,本文以体外培养的血管平滑肌细胞为研究对象,应用Ｎｏｒｔｈｅｒｎ 印迹及基质金属蛋白酶－ ２ 活性酶图分析方法动态观察白细胞介素－ １β、肿瘤坏死因子－ α对血管平滑肌细胞表达基质金属蛋白酶－２ 及骨桥蛋白的影响。结果发现,白细胞介素－１β和肿瘤坏死因子－ α均可显著诱导基质金属蛋白酶－ ２ 及骨桥蛋白的基因表达,血管平滑肌细胞受两种细胞因子刺激１２ ｈ 后,基质金属蛋白酶－２ 及骨桥蛋白ｍＲＮＡ表达活性最高,分别达到对照细胞的３ 倍左右和１０ 倍以上。对细胞培养基基质金属蛋白酶活性进行酶图分析的结果发现,肿瘤坏死因子－α及白细胞介素－１β作用于血管平滑肌细胞１２ 及２４ ｈ 时,基质金属蛋白酶降解明胶的活性约为对照细胞培养基的２ 倍和１．５ 倍。提示这类细胞因子可同时在多位点上对血管平滑肌细胞的迁移与增殖发挥促进作用。     

血小板源性生长因子影响血管弹性蛋白酶表达

探讨球囊损伤后血管平滑肌细胞丝氨酸弹性蛋白酶表达增加的机理。用球囊导管损伤Wistar系雄性大鼠主动脉或颈总动脉。以血小板源性生长因子A和大鼠胰腺丝氨酸弹性蛋白酶的地高辛标记RNA探针进行原位杂交，并用抗5-溴脱氧尿嘧啶抗体进行双重染色。用抗血小板源性生长因子从、抗血小板源性生长因子BB、抗胰腺弹性蛋白酶、抗人增殖细胞核抗原等抗体进行免疫染色或免疫双重染色。电镜观察细胞的超微结构。结果发现：①在球囊损伤后O．5～4h，血小板源性生长因子mRNA表达细胞多于弹性蛋白酶mRNA表达细胞；②增殖细胞和迁移细胞既有血小板源性生长因子mRNA和其蛋白表达，又有弹性蛋白酶mRNA和其蛋白表达；③迁移细胞多为增殖细胞核抗原染色阳性．细胞内可见到核分裂像。提示血小板源性生长因子可能是刺激中膜平滑肌细胞增殖、迁移并使其弹性蛋白酶增加的影响因子之一。     

血小板源生长因子和血管紧张素Ⅱ对血管平滑肌细胞中p57基因表达的影响

为观察血小板源生长因子BB和血管紧张素Ⅱ对血管平滑肌细胞p57蛋白和基因表达的影响及其在血管平滑肌细胞增殖增生中的作用。用贴壁法培养鼠胸主动脉平滑肌细胞,加入血小板源生长因子BB 20ug/L或血管紧张素Ⅱ 1umol/L刺激24h,用Western蛋白印迹法检测p57蛋白水平,用DNA芯片技术检测p57 mRNA的表达量,结果发现,血小板源生长因子BB刺激组p57 mRNA和p57蛋白表达量明显高于血管紧张素Ⅱ刺激组,分别为后者的2．47倍和1．7倍,而血管紧张素Ⅱ刺激组p57蛋白表达量与对照组接近,保持在较低水平,研究结果提示,在血小板源生长因子刺激引起的血管平滑肌细胞增殖过程中p57基因表达明显增高,p57基因的高表达可能起抑制血管平滑细胞过度增殖的作用。     

抗纤维化短肽N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸对大鼠心脏成纤维细胞胶原合成与降解的调节作用

目的探讨N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸（AcSDKP）对血小板源性生长因子（PDGF）诱导的大鼠心脏成纤维细胞增殖、胶原合成和降解代谢的调节作用。方法分离培养新生大鼠心脏成纤维细胞。采用^3H-TdR和。H-脯氨酸掺入法分别检测心脏成纤维细胞增殖与胶原蛋白合成。Western blot法检测心脏成纤维细胞Ⅰ、Ⅲ型胶原蛋白表达和基质金属蛋白酶（MMP）-1蛋白的表达。明胶酶谱法检测心脏成纤维细胞MMP-2和MMP-9活性的表达。结果PDGF促进心脏成纤维细胞增殖、胶原合成,Ⅰ、Ⅲ型胶原表达,以及MMP-2、MMP-9活性和MMP-1表达。AcSDKP对PDGF介导的心脏成纤维细胞增殖、胶原合成均有抑制作用。AcSDKP上调由PDGF介导的心脏成纤维细胞MMP-2、MMP-9活性和MMP-1的表达。结论AcSDKP抑制PDGF介导的心脏成纤维细胞增殖和胶原的合成,上调MMPs活性或表达,促进胶原的降解,这些可能与AcSDKP抗心脏纤维化作用相关。     

The Effect of Ras Inhibition on the Proliferation, Apoptosis and Matrix Metalloproteases Activity in Rat Hepatic Stellate Cells

In vivo inhibition of Ras by its antagonist farnesylthiosalicylic acid (FTS) prevents and reverses liver fibrosis in a rat model. In this study we showed the in vitro effects of Ras inhibition in a rat hepatic stellate cell line, HSC-T6. The IC₅₀ of FTS that inhibited PDGF-induced proliferation was 15 μM. FTS, by itself or in combination with PDGF, induced a three- to fivefold increase in the number of apoptotic stellate cells but did not induce apoptosis in cells cultured with TGFβ1. We observed increased activity of MMP-9 and MMP-2 induced by FTS in combination with PDGF or TGFβ. FTS, alone or in the presence of PDGF and TGFβ, reduced collagen I mRNA expression. In conclusion, the in vivo amelioration of liver fibrosis by FTS may be explained by its ability to inhibit hepatic stellate cell proliferation, induce apoptosis and MMP-2 and MMP-9 activity, and decrease collagen I expression.     

Sinomenine reduces invasion and migration ability in fibroblast-like synoviocytes cells co-cultured with activated human monocytic THP-1 cells by inhibiting the expression of MMP-2, MMP-9, CD147

CD147 expressed by monocytes, macrophages, and synoviocytes cells can stimulate the production of matrix metalloproteinases (MMPs) associated with the development of rheumatoid arthritis (RA). We investigated the effects of Sinomenine (SIN) on invasion and migration ability and gene expression of CD147, MMP-2, MMP-9 of fibroblast-like synoviocytes cells (FLS) co-cultured with activated human monocytic THP-1 cells (A-THP-1) in vitro. SIN is a pure alkaloid extracted from the Chinese medical plant Sinomenium acutum. FLS cells were co-cultured with THP-1 cells which were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA). Cells were treated with different concentrations of SIN. Invasion and migration ability of cells was tested by transwell assays. Western blot analysis and zymographic analysis were adopted to detect the expression of CD147 and MMPs, respectively. RT–PCR was used to determine the expression of mRNA of CD147, MMP-2, and MMP-9. The invasion and migration ability of the co-cultured cells was significantly inhibited by SIN in a concentration-dependent fashion, and at the same time, the levels of CD147, MMP-2, MMP-9 were markedly down-regulated. This inhibitory effect was most notable at concentrations of 0.25 and 1.00 mM (P < 0.01). Our results point to a possible mechanism of SIN on treatment of RA is the inhibitory effect of SIN on cell invasion and migration ability, which strongly correlates with repressing the expression of CD147, MMP-2, and MMP-9.     

槲皮素对人胃癌细胞侵袭和MMP-2表达的影响

目的:观察槲皮素(Quercetin,Que)对人胃癌细胞侵袭的影响,并探讨其可能机制.方法:采用不同浓度的槲皮素处理胃癌BGC-823细胞后,以软琼脂集落培养试验检测癌细胞锚着不依赖性增殖,以Boyden小室模型方法检测癌细胞侵袭能力,采用荧光实时定量PCR检测癌细胞基质金属蛋白酶-2(matrix metallopeptidase-2,MMP-2)基因mRNA水平,以Western blot方法检测癌细胞MMP-2基因蛋白水平变化.结果:不同浓度的胃癌BGC-823细胞经槲皮素处理后,恶性增殖和侵袭能力均明显下降,且呈剂量依赖性(P<0.005,P<0.005).槲皮素处理组MMP-2基因mRNA和蛋白水平均明显下调,且呈时间和浓度依赖性,即随着作用时间的延长和槲皮素作用浓度的增加,MMP-2的mRNA和蛋白水平逐渐下降,差异均有统计学意义(P<0.001,P<0.001).结论:槲皮素可明显抑制胃癌BGC-823细胞侵袭能力,其机制可能与下调MMP-2基因表达有关.     

Differential effects of PDGF-BB on matrix metalloproteases and cytokine release in fibroblasts of Type 2 diabetic patients and normal controls in vitro

AIMS/HYPOTHESIS: The complex process of wound healing is regulated by various growth factors. The systemic character of diabetes mellitus favors the chronification of diabetic wounds. In this study, the in vitro effects of platelet-derived growth factor (PDGF)-BB on the expression of cytokines and matrix metalloproteases (MMPs) in fibroblasts of Type 2 diabetic patients and healthy controls were investigated. METHODS: We studied six Type 2 diabetic patients (mean Hba1(c)=7.5%) and six healthy controls. For proliferation studies, cultivated fibroblasts, prepared from biopsies taken from the thigh, were stimulated with different concentrations of PDGF. After 48 h, the expression of MMPs and cytokines was measured. We analysed the mRNA expression by RT-PCR (TaqMan), tissue protein levels by zymography, and cell supernatant levels by ELISA. RESULTS: Levels of MMP-mRNA were elevated in diabetic fibroblasts compared with healthy controls. At baseline, MMP-2 protein levels were significantly increased in the fibroblast of diabetic patients (P=.019). For MMP-9, a trend towards higher levels (P=.3) was found. After incubation with PDGF, a significant reduction of MMP-9 (P=.01) and MMP-13 (P=.04) was found. Analysis of cytokine release in cell culture supernatant showed elevated levels of interleukin (IL)-8 at baseline conditions. MMP-1 and MMP-2 levels in the supernatant were concentration-dependently reduced. CONCLUSIONS: This study, for the first time, demonstrates elevated MMPs in cultivated fibroblasts (derived from intact skin and not from an open wound) of diabetic patients compared with healthy controls under in vitro conditions. Therefore, our data support the hypothesis of alterations of wound healing in diabetic patients on the cellular level, reflecting the systemic character of the disease.     

In vitro migratory potential of rat quiescent hepatic stellate cells and its augmentation by cell activation.

In liver injury, hepatic stellate cells are considered to depart from the sinusoidal wall and accumulate in the necrotic lesion through migration and proliferation. In this study, we investigated the migratory capacity of quiescent stellate cells in vitro and analyzed the relationship with proliferative response. Freshly isolated stellate cells that were seeded in the upper chamber of Cell Culture Insert (Becton Dickenson, Franklin Lakes, NJ) started to migrate to the lower chamber at 1 day and increased in migration index to 19% at 2 days. Cells in the lower chamber were stretched in shape with many lipid droplets and showed quiescent properties, i.e., negative expression of alpha-smooth muscle actin (alpha-SMA) or platelet-derived growth factor receptor-beta (PDGFR-beta). Migratory capacity in quiescent cells was also shown in the Matrigel-coated insert. Matrix metalloproteinase-2 (MMP-2) messenger RNA expression was low just after isolation, but was enhanced as migration became prominent. Migrating cells further showed higher proliferative activity than resting ones. The presence of PDGF/BB and Kupffer cells accelerated stellate cell migration by the chemotactic mechanism and concurrently augmented proliferation, whereas that of dexamethasone and interferon-gamma (IFN-gamma) attenuated migration as a result of general suppression effects. Compared with quiescent ones, alpha-SMA and PDGFR-beta-positive activated stellate cells obtained by 14-day culture exhibited more rapid and prominent migration, being regulated by mediators in a similar manner as described previously. These data indicate that quiescent stellate cells undergo migration, which is linked to proliferation and enhanced by PDGF/BB and Kupffer cells, suggesting the involvement of this function in the initial phase of development of postnecrotic fibrosis.     

The role of protein-tyrosine phosphorylation and gelatinase production in the migration and proliferation of smooth muscle cells

BACKGROUND: It has been reported that matrix metalloproteinase (MMP) was expressed in coronary arterial atherosclerotic lesions. However, not much is known about the relationship between the production of MMP and the progression of atherosclerosis. PURPOSE AND METHOD: To demonstrate the association between the protein-tyrosine phosphorylation (PTP) and the activation of extracellular MMP in the proliferation and migration of vascular smooth muscle cells (VSMCs), the effect of platelet-derived growth factor (PDGF) and vanadate (an inhibitor of protein-tyrosine phosphatase and an activator of certain protein-tyrosine kinases) on mitogenesis ([3H]thymidine incorporation after 24 hours), migration, PTP (Western blot analysis using anti-phosphotyrosine antibodies), and production of MMP (gelatin zymography) was examined in cultured VSMCs. RESULTS: Both vanadate (1-5 micromol/l) and PDGF (1-10 ng/ml) caused a dose-dependent increase in thymidine incorporation and migration and produced 72-kDa type IV gelatinase (MMP-2) in VSMCs. The combination of vanadate and PDGF resulted in a dose-dependent synergistic effect on thymidine incorporation and MMP-2 production. Western blot analysis revealed that PDGF caused an increase in PTP, extracellular signal-regulated kinases (ERK1, ERK2) and PDGF receptor in VSMCs. Vanadate given together with PDGF induced a marked increase in the intensity of tyrosine phosphorylation in these proteins. Tyrosine kinase inhibitors (genistein and herbimycin A) and a synthetic inhibitor of MMP (1,10-phenanthroline) and an anti-MMP-2 neutralizing antibody inhibited the mitogenic effect induced by vanadate and/or PDGF. CONCLUSIONS: The data suggest that the proliferation and migration of cultured VSMCs was closely related to the stimulation of MMP-2 production that was induced through activation of PTK.     

Effects of PDGF-C and PDGF-D on monocyte migration and MMP-2 and MMP-9 expression

Background and aimsAtherosclerosis is a chronic inflammatory process involving the activity of several cytokines and growth factors. Platelet-derived growth factor-A (PDGF-A) and PDGF-B are important mitogens and chemoattractants for monocytes as well as smooth muscle cells. We sought to identify the role of PDGF-C and PDGF-D, two new members of the PDGF family, in monocyte migration and differentiation. We also assessed their effects in regulating matrix metalloproteinase-2 (MMP-2) and MMP-9, which are important for cell migration.Methods and resultsPDGF-C and PDGF-D were expressed in macrophages, smooth muscle cells, and endothelial cells in human atherosclerotic plaques, as shown by immunohistochemical analysis. PDGF-C and PDGF-D mRNA and protein expression was induced after differentiation of THP-1 monocytes to macrophages, and both PDGF-C and PDGF-D induced MMP-9 mRNA expression in a concentration-dependent manner. Treatment of cells with PDGF-C or PDGF-D enhanced the secretion of MMP-2 and MMP-9 in a cell-dependent manner. In a migration assay using a Boyden chamber with 8 μm pore size, PDGF-C and PDGF-D attracted THP-1 monocytes in a concentration-dependent manner.ConclusionsOur data suggest that PDGF-C and PDGF-D, like PDGF-A and PDGF-B, play important roles in atherosclerosis by stimulating MMP activity and influencing monocyte migration.