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首页> 外文期刊>Journal of atherosclerosis and thrombosis. >Trichostatin A, an inhibitor of histone deacetylase, inhibits smooth muscle cell proliferation via induction of p21(WAF1).
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Trichostatin A, an inhibitor of histone deacetylase, inhibits smooth muscle cell proliferation via induction of p21(WAF1).

机译：Trichostatin A是组蛋白脱乙酰基酶的抑制剂，可通过诱导p21（WAF1）抑制平滑肌细胞增殖。

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The proliferation of vascular smooth muscle cells (VSMCs) can contribute to a variety of pathological states, including atherosclerosis and post-angioplasty restenosis. The p21(WAF1) cyclin-dependent kinase inhibitor regulates cell-cycle progression, senescence, and differentiation in injured blood vessels. Histone deacetylase (HDAC) inhibitors have shown utility in controlling proliferation in a wide range of tumor cell lines, possibly by inducing the expression of p21(WAF1). Our goal was to investigate the effect of trichostatin A (TSA), a specific and potent HDAC inhibitor, on the proliferation of vascular smooth muscle cells (VSMCs) isolated from rat thoracic aorta. TSA suppressed the HDAC activity of VSMCs in a dose-dependent manner and inhibited VSMC proliferation as demonstrated by cell number counting and the degree of [3H] thymidine incorporation. Further, TSA reduced the phosphorylation of Rb protein, a regulator of cell-cycle progression. TSA treatment also induced the expression of p21(WAF1) but not of p16(INK4), p27(KIP1) or p53. Finally, TSA inhibited HDAC activity of VSMCs from p21(WAF1) knock-out mice but had no effect on VSMC proliferation in these animals. In conclusion, TSA inhibits VSMC proliferation via the induction of p21(WAF1) expression and subsequent cell-cycle arrest with reduction of the phosphorylation of Rb protein at the G1-S phase.
机译：血管平滑肌细胞（VSMC）的增殖可导致多种病理状态，包括动脉粥样硬化和血管成形术后再狭窄。 p21（WAF1）细胞周期蛋白依赖性激酶抑制剂可调节受损血管中的细胞周期进程，衰老和分化。组蛋白脱乙酰基酶（HDAC）抑制剂已显示出可通过诱导p21（WAF1）的表达来控制各种肿瘤细胞的增殖。我们的目标是研究曲古抑菌素A（TSA）（一种特异且有效的HDAC抑制剂）对分离自大鼠胸主动脉的血管平滑肌细胞（VSMC）增殖的影响。 TSA以剂量依赖性方式抑制VSMC的HDAC活性，并抑制VSMC增殖，如细胞数计数和[3H]胸苷掺入程度所证明。此外，TSA减少了Rb蛋白的磷酸化，Rb蛋白是细胞周期进程的调节剂。 TSA处理还诱导了p21（WAF1）的表达，但不诱导p16（INK4），p27（KIP1）或p53的表达。最后，TSA抑制了来自p21（WAF1）基因敲除小鼠的VSMC的HDAC活性，但对这些动物中的VSMC增殖没有影响。总而言之，TSA通过诱导p21（WAF1）表达和随后的细胞周期停滞（通过减少G1-S期Rb蛋白的磷酸化作用）来抑制VSMC增殖。

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