ROLE OF AGE IN VASCULAR SMOOTH MUSCLE CELL MIGRATION AND INVASION

许多血管疾病的发生和发展依赖于 血管平滑肌细胞的迁移和增殖 它们与细胞外基质(ECM)相互作用。发病率和 血管疾病的患病率随着年龄的增长而增加，影响 大约50%的男性(到65岁)和女性(到75岁)。我们有 先前发现，增殖的VSMC会积极降解和 侵入重建的基底膜屏障(模拟为 围绕单个VSMC并将其分开的基底膜 从内弹力板形式的内皮细胞中 Vivo)对PDGF的反应，而血清的迁移和侵袭 饥饿/分化的VSMC低于20%(p<0.001)， 增殖细胞的数量。我们通过以下方式展示了VSMC迁移 这种细胞外基质屏障需要72kD的IV型明胶酶。在这个项目中 我们调查了迁移/侵袭性、增殖性和 幼年(3~6mo)和幼年VSMC的分化行为 老年(24mo龄)大鼠。VSMC的两个群体(新内膜和中膜) 各年龄组球囊导管损伤后取材。 早期传代(P2-P5)年轻新生内膜VSMC迁移能力增加75% 与(P2-P5)年轻的内侧VSMC相比，具有侵袭性行为。在… 晚期传代(P6-P16)年轻的中膜和年轻的新生内膜VSMC 类似的迁徙和入侵特征。相比之下，旧的 内侧(P2-P5)表现为攻击性、迁移性和侵袭性行为 陈旧性新生内膜(P2~P5)。当所有四个组的VSMC都在增长时 被捕后，它们的迁徙和入侵行为不到20% 年龄/表型相匹配的增殖细胞。我们观察到 72kD IV型明胶酶活性与受体酪氨酸的差异 增殖期和增殖期PDGF对蛋白激酶(RTK)激活的影响 应用VSMC基因标记物的分化VSMC未来研究 分化和增殖的VSMC，如钙蛋白、芯片28和 骨桥蛋白和72kD IV型明胶酶的表达 激活应该为理解以下内容提供重要信息 迁移/侵袭行为的年龄相关行为差异 VSMC的。

The development and progression of many vascular diseases depend on the migration and proliferation of vascular smooth muscle cells (VSMC) and their interaction with extracellular matrix (ECM). The incidence and prevalence of vascular disease increase with age, affecting approximately 50% of men (by age 65) and women (by age 75). We have found previously that proliferating VSMC aggressively degrade and invade a reconstituted basement membrane barrier (modeled to mimic the basement membrane which surrounds individual VSMC and separates them from endothelial cells in the form of the internal elastic lamina in vivo) in response to PDGF, while the migration and invasion of serum- starved/differentiated VSMC was less than 20% (p less than 0.001) that of proliferating cells. We demonstrated that VSMC migration through this ECM barrier requires 72 kD Type IV gelatinase. In this project we investigated the migratory/invasive, 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. Early passage (P2-P5) young neointimal VSMC exhibit 75% more migratory and invasive behavior as compared with (P2-P5) young medial VSMC. At later passages (P6-P16) young medial and young neointimal VSMC exhibit similar migratory and invasive characteristics. In contrast, old medial (P2-P5) show as aggressive migratory and invasive behavior as old neointimal (P2-P5). When VSMC from all four groups were growth arrested, their migratory and invasive behavior was less than 20% that of age/phenotype matched proliferating cells. We have observed differences in active 72 kD Type IV gelatinase and in receptor tyrosine kinase (RTK) activation in response to PDGF between proliferating and differentiated VSMC Future studies employing gene markers of differentiated and proliferating VSMC such as calponin, CHIP 28 and Osteopontin as well as 72 kD Type IV gelatinase expression and activation should provide important information in understanding these age-associated behavioral differences in migratory/invasive behavior of VSMC.