首页> 外文期刊>American Journal of Physiology >Effect of stent coating alone on in vitro vascular smooth muscle cell proliferation and apoptosis.
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Effect of stent coating alone on in vitro vascular smooth muscle cell proliferation and apoptosis.

机译:单独使用支架涂层对体外血管平滑肌细胞增殖和凋亡的影响。

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摘要

Synthetic polymers, like methacrylate (MA) compounds, have been clinically introduced as inert coatings to locally deliver drugs that inhibit restenosis after stent. The aim of the present study was to evaluate the effects of MA coating alone on vascular smooth muscle cell (VSMC) growth in vitro. Stainless steel stents were coated with MA at the following doses: 0.3, 1.5, and 3 ml. Uncoated/bare metal stents were used as controls. VSMCs were cultured in dishes, and a MA-coated stent or an uncoated bare metal stent was gently added to each well. VSMC proliferation was assessed by bromodeoxyuridine (BrdU) incorporation. Apoptosis was analyzed by three distinct approaches: 1) annexin V/propidium iodide fluorescence detection; 2) DNA laddering; and 3) caspase-3 activation and PARP cleavage. MA-coated stents induced a significant decrease of BrdU incorporation compared with uncoated stents at both the low and high concentrations. In VSMCs incubated with MA-coated stents, annexin V/propidium iodide fluorescence detection showed a significant increase in apoptotic cells, which was corroborated by the typical DNA laddering. Apoptosis of VSMCs after incubation with MA-coated stents was characterized by caspase-3 activation and PARP cleavage. The MA-coated stent induced VSMC growth arrest by inducing apoptosis in a dose-dependent manner. Thus MA is not an inert platform for eluting drugs because it is biologically active per se. This effect should be taken in account when evaluating an association of this coating with antiproliferative agents for in-stent restenosis prevention.
机译:临床上已经引入了诸如甲基丙烯酸酯(MA)化合物之类的合成聚合物作为惰性涂层,以局部递送抑制支架后再狭窄的药物。本研究的目的是评估单独的MA涂层对体外血管平滑肌细胞(VSMC)生长的影响。用以下剂量的MA涂覆不锈钢支架:0.3、1.5和3 ml。使用未涂覆/裸露的金属支架作为对照。在培养皿中培养VSMC,并向每个孔中轻轻添加MA涂层支架或未涂层的裸金属支架。通过掺入溴脱氧尿苷(BrdU)来评估VSMC增殖。通过三种不同的方法分析细胞凋亡:1)Annexin V /碘化丙啶荧光检测; 2)DNA梯形图; 3)caspase-3激活和PARP裂解。在低浓度和高浓度下,与未涂层的支架相比,MA涂层的支架引起的BrdU掺入量显着降低。在装有MA涂层支架的VSMC中,膜联蛋白V /碘化丙啶荧光检测显示凋亡细胞显着增加,这通过典型的DNA梯形得到证实。与MA包被的支架一起孵育后,VSMC的凋亡以caspase-3激活和PARP裂解为特征。涂有MA的支架通过以剂量依赖的方式诱导细胞凋亡来诱导VSMC生长停滞。因此,MA并不是一种洗脱药物的惰性平台,因为它本身具有生物活性。在评估该涂层与抗增生剂的结合以预防支架内再狭窄时,应考虑到这种效果。

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