Recent findings demonstrate that adventitial fibroblasts are endowed with several characteristics previously attributed to medial smooth muscle cells. Rapid activation of adventitial fibroblast, which proliferate, mig...Recent findings demonstrate that adventitial fibroblasts are endowed with several characteristics previously attributed to medial smooth muscle cells. Rapid activation of adventitial fibroblast, which proliferate, migrate, and undergo differentiation to myofibroblasts after balloon induced coronary injury. Myofibroblasts are involved in remodeling of adventitia and may contribute to the formation of the neointima. This review will illustrate the morphologic features, phenotypic modulation of myofibroblasts and its role in vascular remodeling, which raises the possibility of targeted therapies.展开更多
血管外膜成纤维细胞迁移参与形成新生内膜是一些血管疾病的共同发病过程。研究高血压动物模型的外膜成纤维细胞是否与对照组不同将有利于阐述高血压血管重塑的机制。本实验比较自发性高血压大鼠(spontaneously hy-pertensive rats,SHR)...血管外膜成纤维细胞迁移参与形成新生内膜是一些血管疾病的共同发病过程。研究高血压动物模型的外膜成纤维细胞是否与对照组不同将有利于阐述高血压血管重塑的机制。本实验比较自发性高血压大鼠(spontaneously hy-pertensive rats,SHR)与正常对照大鼠(Wistar-Kyoto rats,WKY)的血管外膜成纤维细胞在体外培养条件下迁移能力的差别,并对其机制进行了探讨。采用大鼠胸主动脉的培养血管外膜成纤维细胞,用Transwell技术测定培养细胞的迁移能力。用实时定量PCR技术检测mRNA表达。结果表明,在血清和bFGF趋化作用下,SHR培养血管外膜成纤维细胞的迁移活性显著强于WKY(每个视野平均迁移细胞数目,血清:35.20±5.26 vs 22.2±3.27,P<0.05;bFGF:30.23±4.54vs 19.20±4.47,P<0.05)。进一步研究发现,SHR培养血管外膜成纤维细胞中的骨桥蛋白(osteopontin,OPN)mRNA水平显著高于WKY(1863.23±43.91 vs 326.24±68.29,P<0.01)。反义OPN(100 μmol/L)对血清诱导的SHR血管外膜成纤维细胞迁移有抑制作用(每个视野平均迁移细胞数目 38.60±5.98 vs 26.61±3.84,P<0.05)。而正义及错配义OPN组均无此效应。反义OPN对SHR细胞迁移的抑制作用呈浓度依赖性。上述结果证实SHR培养血管外膜成纤维细胞的迁移能力强于WKY。展开更多
文摘Recent findings demonstrate that adventitial fibroblasts are endowed with several characteristics previously attributed to medial smooth muscle cells. Rapid activation of adventitial fibroblast, which proliferate, migrate, and undergo differentiation to myofibroblasts after balloon induced coronary injury. Myofibroblasts are involved in remodeling of adventitia and may contribute to the formation of the neointima. This review will illustrate the morphologic features, phenotypic modulation of myofibroblasts and its role in vascular remodeling, which raises the possibility of targeted therapies.
基金This work was supported by the National Natural Science foundation of China(M3007030330270544).
文摘血管外膜成纤维细胞迁移参与形成新生内膜是一些血管疾病的共同发病过程。研究高血压动物模型的外膜成纤维细胞是否与对照组不同将有利于阐述高血压血管重塑的机制。本实验比较自发性高血压大鼠(spontaneously hy-pertensive rats,SHR)与正常对照大鼠(Wistar-Kyoto rats,WKY)的血管外膜成纤维细胞在体外培养条件下迁移能力的差别,并对其机制进行了探讨。采用大鼠胸主动脉的培养血管外膜成纤维细胞,用Transwell技术测定培养细胞的迁移能力。用实时定量PCR技术检测mRNA表达。结果表明,在血清和bFGF趋化作用下,SHR培养血管外膜成纤维细胞的迁移活性显著强于WKY(每个视野平均迁移细胞数目,血清:35.20±5.26 vs 22.2±3.27,P<0.05;bFGF:30.23±4.54vs 19.20±4.47,P<0.05)。进一步研究发现,SHR培养血管外膜成纤维细胞中的骨桥蛋白(osteopontin,OPN)mRNA水平显著高于WKY(1863.23±43.91 vs 326.24±68.29,P<0.01)。反义OPN(100 μmol/L)对血清诱导的SHR血管外膜成纤维细胞迁移有抑制作用(每个视野平均迁移细胞数目 38.60±5.98 vs 26.61±3.84,P<0.05)。而正义及错配义OPN组均无此效应。反义OPN对SHR细胞迁移的抑制作用呈浓度依赖性。上述结果证实SHR培养血管外膜成纤维细胞的迁移能力强于WKY。
基金This work was supported by the National Basic Research Priorities Programme of China(No.2004CB518603)and Key Project of Basic Research from Shanghai Science and Technology Committee(No.05JC14038).
文摘我们以往的研究表明,TGF-β1可以诱导血管外膜成纤维细胞(adventitiai fibroblasts,AFs)向肌成纤维细胞(myo- fibroblasts,MFs)分化。为寻找可能涉及MF分化的基因,本实验采用寡核苷酸芯片技术动态检测细胞表型转化过程中基因表达的变化,实时定量RT-PCR验证芯片结果。在芯片上的15866条总探针组中,2121个探针组在TGF-β1刺激后至少一个时间点的表达发生2倍以上变化,其中1318个基因表达上调,761个基因表达下调,还有少数基因(42个)在不同的时间点既有上调又有下调表达。在1231个已知功能基因中,分泌磷蛋白1(secreted phosphoprotein 1,APPI)、Rho- associated coiled-coil forming kinase 2(ROCK2)的表达趋势与标志基因α-平滑肌肌动蛋白(α-SM-actin)的表达趋势相同,TGF-β1诱导MF分化过程中上调了电压门控性钾通道Shal家族成员2(potassium voltage-gated channel,Shal-related family and mem- ber 2,KCND2)的表达,这些基因参与了MF的分化；此外,还发现内皮素1(endothelin 1,EDN1)、补体成分、NADPH氧化酶4(NADPH oxidase 4,NOX4)和NAD(P)H dehydrogenase,quinone 1(NQO1)可能参与了MF分化。本实验用寡核苷酸芯片技术验证了通过其它技术证实的同MF分化相关的基因,并发现了新的涉及该过程的基因,基因表达谱研究有利于鉴定参与细胞分化的基因和通路。
