ROLE OF AGE IN VASCULAR SMOOTH MUSCLE CELL MIGRATION AND INVASION

血管平滑肌细胞(VSMCs)的迁移是动脉粥样硬化中的一个重要事件。 许多血管疾病的发病机制。该病的发病率和流行率 血管疾病随着年龄的增长而增加，影响大约50%的男性(通过 65岁)和女性(到75岁)。我们调查了迁徙， 青年(AGE)来源的VSMC的增殖和分化行为 3-6mo)和老年(24mo)大鼠。VSMC的两个群体(新生内膜和 各年龄组球囊导管损伤后取内侧动脉。 新血管内膜和中膜VSMCs的细胞形态和形态不同 关于基因表达的。我们在这里展示了它们的体外迁移作为对 到PDGF的渐变也不同。具体地说，早期通过(P2-P5)年长 与(P2-P5)相比，内侧VSMC表现出75%的迁移行为 年轻的内侧VSMC。后半段(P&gt；10)年轻的中间人和老年的中间人 VSMC具有相似的迁移特性。另外，杨格 新生内膜(P2-P5)细胞的迁移率比年轻的中膜(P2-P5)细胞大75%。 P5)细胞。两组人的增殖率和细胞大小相似， 即刻早期基因c-fos和je表达上调 (MCP-1)对PDGF的响应。中层细胞表现出钝的 细胞内钙离子对离子霉素的响应及细胞内钙离子浓度下降50% CamkinaseII的激活与新生内膜细胞的比较。 有趣的是，将Calponin正义DNA(A)导入新生内膜细胞 中间细胞的遗传标记)使它们较少迁移，而反义 Calponin没有显示出任何效果。当所有群体的VSMC增长受阻时， 他们的迁徙行为不到年龄/表型匹配的20% 正在增殖的细胞。除PDGF外，年轻增殖期的迁移 细胞需要自分泌的生长因子--碱性成纤维细胞生长因子。奥尔 相比之下，单元格似乎不需要这个额外的因素 要发生的迁移。我们观察到72kD的IV型明胶酶和 受体酪氨酸激酶(RTK)激活对PDGF的反应是依赖的 关于细胞的表型状态，如报告278-04和815-02所详述。 未来的研究表征这些差异，并进一步采用 每组细胞特有的遗传标记应该提供重要的 了解这些与年龄相关的行为差异的信息 VSMC 迁移。

The migration of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of many vascular disease. The incidence and prevalence of vascular disease increase with age, affecting approximately 50% of men (by age 65) and women (by age 75). We investigated the migratory, proliferative, and differentiative behavior of VSMC derived from young (age 3-6 mo) and old (age 24 mo) rats. Two populations of VSMC (neointimal and medial) were obtained following balloon catheter injury for each age group. Neointimal and medial VSMCs differ in their cellular morphology and pattern of gene expression. We show here that their in vitro migration in response to PDGF gradient differs, as well. Specifically, early passage (P2-P5) old medial VSMC exhibit 75% more migratory behavior as compared with (P2-P5) young medial VSMC. At later passages (P>10) young medial and old medial VSMC exhibit similar migratory characteristics. In addition, young neointimal (P2-P5) cells show 75% greater migration than young medial (P2- P5) cells. Both groups showed similar proliferation rates and cell sizes, and both upregulated expression of the immediate-early genes,c-fos and JE (MCP-1) in response to PDGF. The medial cells exhibited a blunted intracellular calcium in response to Ionomycin and a 50% reducti on in CamKinaseII activation as compared to neointimal cells. Interestingly, transfection of neointimal cells with Calponin sense DNA (a genetic marker of medial cells) rendered them less migratory while antisens Calponin showed no effect. When VSMC from all groups were growth-arrested, their migratory behavior was less than 20% that of age/phenotype matched proliferating cells. In addition to PDGF, migration of young proliferating cells requires the autocrine production of the growth factor, basic FGF. Ol cells,in contrast, do not appear to require this additional factor for migration to occur. We have observed that 72 kD Type IV gelatinase and receptor tyrosine kinase (RTK) activation in response to PDGF is dependent on phenotypic state of the cell as detailed in reports 278-04 and 815-02. Future studies characterizing these differences and further employing genetic markers specific to each group of cells should provide important information in understanding these age-associated behavioral differences in VSMC migration.