L-calcium channel blockade induced by diltiazem inhibits proliferation, migration and F-actin membrane rearrangements in human vascular smooth muscle cells stimulated with insulin and IGF-1.
L-calcium channel blockade induced by diltiazem inhibits proliferation, migration and F-actin membrane rearrangements in human vascular smooth muscle cells stimulated with insulin and IGF-1.
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发表时间：
2003-09
影响因子：
0.8
通讯作者：
A. Ruiz-Torres;R. Lozano;J. Melón;R. Carraro
中科院分区：
文献类型：
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作者：
A. Ruiz-Torres;R. Lozano;J. Melón;R. Carraro
在动脉粥样硬化斑块形成过程中，平滑肌细胞（SMC）必须改变其分化表型才能增殖、迁移和合成胶原蛋白。这些表型变化是由胰岛素和IGF-1刺激的，我们研究了地尔硫卓产生的l型钙通道阻断剂对这些变化的影响。用溴脱氧尿苷DNA结合法测定有丝分裂活性，用Boyden室趋化指数测定迁移能力，用免疫荧光法测定与SMC运动相关的细胞骨架变化。地尔硫卓(10（-7)-10(-6)M）比igf -1更有效地降低胰岛素诱导的人血管SMC有丝分裂活性，但在10(-5)M时，抑制效果相似。地尔硫卓在基础条件下（p < 0.05）和添加胰岛素（p = 0.0001）和IGF-1 （p < 0.0001）后也显示出明显的迁移能力抑制。最后，地尔硫卓以相似的方式抑制胰岛素和IGF-1诱导的膜皱褶，并在大鼠主动脉SMC中获得类似的结果。我们得出结论，阻断l型钙通道的物质，如地尔硫卓，可以抑制体内导致SMC形成动脉粥样硬化斑块的过程。
During the atheroma plaque formation, smooth muscle cells (SMC) have to change their differentiated phenotype in order to proliferate, migrate and synthesize collagen. These phenotypic changes are stimulated by insulin and IGF-1, and we have studied the effect of L-type calcium channel blockade produced by diltiazem on such changes. Mitotic activity was measured using bromodeoxyuridine DNA incorporation, the migration capability as chemotaxis index in a Boyden chamber, and cytoskeleton changes related to SMC movement in immunofluorescence studies. Diltiazem (10(-7)-10(-6) M) reduced insulin-induced mitotic activity in cultured human vascular SMC more effectively than in IGF-1-induced mitotic activity, but at 10(-5) M, the inhibitory effects were similar. Diltiazem also showed a clear inhibition of migration ability, both under basal conditions (p < 0.05) and after addition of insulin (p = 0.0001) and IGF-1 (p < 0.0001). Finally, diltiazem inhibited membrane ruffling induced both by insulin and IGF-1 in a similar manner, and similar results were obtained with SMC from rat aorta. We conclude that substances blocking the L-type calcium channels such as diltiazem, could inhibit those processes which in vivo lead SMC to form the atheroma plaque.