Rat and human aortic smooth muscle cells display differing migration and matrix metalloproteinase activities in response to dexamethasone
Rat and human aortic smooth muscle cells display differing migration and matrix metalloproteinase activities in response to dexamethasone
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DOI：
10.1067/mva.2002.123332
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发表时间：
2002-06-01
影响因子：
4.3
通讯作者：
Gelabert, HA
中科院分区：
文献类型：
--
作者：
Pross, C;Farooq, MM;Gelabert, HA
目的：类固醇激素地塞米松抑制大鼠血管内膜增生，但对人血管内膜增生无明显影响。本研究探讨地塞米松对大鼠和人类平滑肌细胞迁移和基质金属蛋白酶（MMP）activity.Methods：大鼠主动脉平滑肌细胞从Sprague-Dawley大鼠收获的差异影响。人主动脉平滑肌细胞获自Clonetics。Boyden室迁移试验用化学引诱物（血小板衍生生长因子）和不同浓度的地塞米松（10（-9）至10（-5）mol/L）进行。培养基的酶谱被用来评估MMP活性，和Western blot分析用于定量的MMP-2和MMP-2的组织抑制剂（TIMP-2）的secretion.Results：地塞米松抑制大鼠主动脉平滑肌细胞迁移的剂量依赖性的方式。地塞米松浓度的增加不会影响人主动脉平滑肌细胞迁移。地塞米松以剂量依赖性方式抑制大鼠主动脉平滑肌细胞MMP-2活性，地塞米松对人主动脉平滑肌细胞MMP-2活性无影响。MMP-2分泌抑制地塞米松在大鼠主动脉平滑肌细胞，但在人主动脉平滑肌细胞保持不变。地塞米松增加大鼠主动脉平滑肌细胞TIMP-2的分泌，而人主动脉平滑肌细胞TIMP-2的分泌保持恒定。结论：地塞米松抑制大鼠主动脉平滑肌细胞迁移、MMP-2活性和MAP-2的分泌，并增加TIMP-2的分泌。在人主动脉平滑肌细胞中未观察到这些效应。这些发现可以解释为什么地塞米松在动物模型中抑制新生内膜增生，但在人类中无效。体外抑制人平滑肌细胞迁移可能有助于预测未来治疗药物治疗人新生内膜增生的有效性。
Objective: The steroid dexamethasone inhibits neointimal hyperplasia development in rats but not in humans. This study investigates the differential effects of dexamethasone on rat and human smooth muscle cell migration and matrix metalloproteinase (MMP) activity.Methods: Rat aortic smooth muscle cells were harvested from Sprague-Dawley rats. Human aortic smooth muscle cells were obtained from Clonetics. Boyden chamber migration assays were performed with chemoattractant (platelet-derived growth factor) and varying concentrations of dexamethasone (10(-9) to 10(-5) mol/L). Zymography of culture media was used to assess MMP activity, and Western blot analysis was used for quantification of MMP-2 and tissue inhibitor of MMP-2 (TIMP-2) secretion.Results: Dexamethasone inhibits rat aortic smooth muscle cell migration in a dose-dependent fashion. An increase in concentrations of dexamethasone does not effect human aortic smooth muscle cell migration. Rat aortic smooth muscle cell MMP-2 activity is inhibited with dexamethasone in a dose-dependent fashion, and human aortic smooth muscle cell MMP-2 activity is unchanged with dexamethasone. MMP-2 secretion is inhibited with dexamethasone in rat aortic smooth muscle cells but remains unaltered in human aortic smooth muscle cells. Dexamethasone increases rat aortic smooth muscle cell TIMP-2 secretion, and human aortic smooth muscle cell TIMP-2 secretion remains constant.Conclusion: Dexamethasone inhibits rat aortic smooth muscle cell migration, MMP-2 activity, and MAP-2 secretion and increases TIMP-2 secretion. These effects are not observed in human aortic smooth muscle cells. These findings may explain why dexamethasone inhibits neointimal hyperplasia in animal models but is ineffective in humans. Inhibition of human smooth muscle cell migration in vitro may be useful in predicting the effectiveness of future therapeutic agents for treatment of neointimal hyperplasia in humans.