Methotrexate Therapy Promotes Cell Coverage and Stability in in-Stent Neointima
Methotrexate Therapy Promotes Cell Coverage and Stability in in-Stent Neointima
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DOI：
10.1007/s10557-020-07121-7
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发表时间：
2021-01
影响因子：
3.4
通讯作者：
Xianglan Liu;Ruoxi Zhang;G. Fu;Yong Sun;Jian Wu;Maomao Zhang;Jinwei Tian;X. Gu;Yang Zheng;Chengming Shi;J. Hou;Bo Yu
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文献类型：
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作者：
Xianglan Liu;Ruoxi Zhang;G. Fu;Yong Sun;Jian Wu;Maomao Zhang;Jinwei Tian;X. Gu;Yang Zheng;Chengming Shi;J. Hou;Bo Yu
目的药物洗脱支架释放的抗增殖药物延迟了细胞覆盖和血管愈合，增加了晚期支架血栓形成的风险。我们评估了全身性甲氨蝶呤（MTX）对细胞覆盖率的潜在影响，体内和体外的血管愈合和炎症激活。方法我们在兔支架模型中的右颈总动脉中应用MTX，以使用连续光学相干断层扫描（OCT）分析来确定对细胞覆盖和炎症激活的影响，并阐明MTX在人脐静脉内皮细胞（HUVECs）中的分子机制。结果低剂量MTX可促进支架细胞覆盖和血管愈合，支架植入4周时支架未覆盖率（%）和支架未覆盖率（%）明显降低。MTX组还表现出较低的异质性、微血管和每支柱低信号强度层的发生率，表明支架植入12周时新生内膜不稳定。在体外，低剂量MTX通过靶向磷酸肌醇3-激酶（PI 3 K）/AKT信号通路，强烈抑制HUVEC凋亡，促进增殖，抑制炎症激活。结论低剂量MTX可能是支架植入后靶向炎症通路，通过抑制炎症反应促进早期细胞覆盖和新生内膜稳定的关键手段。
PurposeAnti-proliferative drugs released from drug-eluting stents delay cell coverage and vascular healing, which increases the risk of late stent thrombosis. We assessed the potential effects of systemic methotrexate (MTX) on cell coverage, vascular healing and inflammation activation in vivo and in vitro.MethodsWe applied MTX in the right common carotid artery in a rabbit stenting model to determine the impact on cell coverage and inflammation activation using a serial optical coherence tomography (OCT) analysis and elucidated the molecular mechanism of MTX in human umbilical vein endothelial cells (HUVECs).ResultsLow-dose MTX promoted the development of cell coverage and vascular healing, which was associated with fewer uncovered struts (%) and cross-sections with any uncovered struts (%) at 4 weeks of stenting. The MTX group also exhibited lower rates of heterogeneity, microvessels and per-strut low-signal-intensity layers, indicating neointimal instability at 12 weeks of stenting. In vitro, low-dose MTX strongly inhibited HUVEC apoptosis, promoted proliferation and inhibited inflammatory activation by targeting the phosphoinositide 3-kinase (PI3K)/AKT signalling pathway.ConclusionLow-dose MTX may be a key means of promoting early cell coverage via the inhibition of the inflammatory response and stability of neointima by targeting inflammatory pathways after stent implantation.