Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
MOE Key Laboratory of Macromolecule Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
J Mater Chem B. 2022 Apr 6;10(14):2454-2462. doi: 10.1039/d1tb01828k.
Thrombus and restenosis after stent implantation are the major complications because traditional drugs such as rapamycin delay the process of endothelialization. Nitric oxide (NO) is mainly produced by endothelial nitric oxide synthase (eNOS) on the membrane of endothelial cells (ECs) in the cardiovascular system and plays an important role in vasomotor function. It strongly inhibits the proliferation of smooth muscle cells (SMCs) and ameliorates endothelial function when ECs get hurt. Inspired by this, introducing NO to traditional stent coating may alleviate endothelial insufficiency caused by rapamycin. Here, we introduced SNAP as the NO donor, mimicking how NO affects , into rapamycin coating to alleviate endothelial damage while inhibiting SMC proliferation. Through wicking effects, SNAP was absorbed into a hierarchical coating that had an upper porous layer and a dense polymer layer with rapamycin at the bottom. Cells were cultured on the coatings, and it was observed that the injured ECs were restored while the growth of SMCs further diminished. Genome analysis was conducted to further clarify possible signaling pathways: the effect of cell growth attenuated by NO may cause by affecting cell cycle and enhancing inflammation. These findings supported the idea that introducing NO to traditional drug-eluting stents alleviates incomplete endothelialization and further inhibits the stenosis caused by the proliferation of SMCs.
支架植入术后的血栓和再狭窄是主要并发症，因为传统药物如雷帕霉素会延迟内皮化过程。一氧化氮（NO）主要由心血管系统内皮细胞（ECs）的膜上的内皮型一氧化氮合酶（eNOS）产生，在血管运动功能中发挥重要作用。当 ECs 受到伤害时，它强烈抑制平滑肌细胞（SMCs）的增殖并改善内皮功能。受此启发，将 NO 引入传统支架涂层中可能会减轻雷帕霉素引起的内皮功能不全。在这里，我们引入 SNAP 作为 NO 供体，模拟 NO 对细胞的影响，将其引入雷帕霉素涂层中，在抑制 SMC 增殖的同时减轻内皮损伤。通过芯吸作用，SNAP 被吸收到具有上层多孔层和底部具有雷帕霉素的致密聚合物层的分层涂层中。将细胞培养在涂层上，观察到受伤的 ECs 得到恢复，而 SMCs 的生长进一步减少。进行了基因组分析以进一步阐明可能的信号通路：NO 对细胞生长的影响可能是通过影响细胞周期和增强炎症来实现的。这些发现支持了这样一种观点，即向传统的药物洗脱支架中引入 NO 可以减轻不完全的内皮化，并进一步抑制由 SMC 增殖引起的狭窄。
