Coronary artery disease (CAD) is the most common cardiovascular disorder. Vascular surgery strategies for coronary revascularization (either percutaneous or open) show a high rate of failure because of restenosis of the vessel, due to phenotypic switch of vascular smooth muscle cells (VSMCs) leading to proliferation and migration. We have previously reported that the inhibition of Kv1.3 channel function with selective blockers represents an effective strategy for the prevention of restenosis in human vessels used for coronary angioplasty procedures. However, delivery systems for controlled release of these drugs have not been investigated. Here we tested the efficacy of several formulations of elastin like recombinamers (ELRs) hydrogels to deliver the Kv1.3 blocker PAP-1 in various restenosis models. The dose and time course of PAP-1 release from ELRs click hydrogels was able to inhibit human VSMC proliferation in vitro as well as remodeling of human vessels in organ culture and restenosis in in vivo models. We conclude that this combination of active compound and advanced delivery method could improve the outcomes of vascular surgery in patients.

Statement of Significance

Vascular surgery strategies for coronary revascularization show a high rate of failure, because of occlusion (restenosis) of the vessel, due to vascular smooth muscle cells proliferation and migration. We have previously reported that blockers of Kv1.3 channels represent an effective anti-restenosis therapy, but delivery systems for their controlled release have not being explored. Here we tested the efficacy of several formulations of elastin like recombinamers (ELRs) hydrogels to deliver the Kv1.3 blocker PAP-1 in various restenosis models, both in vivo and in vitro, and also in human vessels. We demonstrated that combination of active compound and advanced delivery method could improve the outcomes of vascular surgery in patients.

中文翻译：

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基于弹性蛋白的重组体释放Kv1.3阻滞剂以预防内膜增生的装置：一项体外和体内研究。

冠状动脉疾病（CAD）是最常见的心血管疾病。冠状动脉血管重建术（经皮或开放性）的血管外科手术策略显示，由于血管再狭窄，血管平滑肌细胞（VSMC）的表型转换导致增殖和迁移，失败率很高。我们以前曾报道过，用选择性阻滞剂抑制Kv1.3通道功能代表了一种有效的策略，可预防用于冠状动脉成形术的人血管再狭窄。但是，尚未研究用于控制释放这些药物的递送系统。在这里，我们测试了多种弹性蛋白（例如重组蛋白（ELRs）水凝胶）在各种再狭窄模型中递送Kv1.3阻断剂PAP-1的功效。体外以及器官模型中人类血管的重塑和体内模型中的再狭窄。我们得出的结论是，这种活性化合物和先进的输送方法相结合可以改善患者血管手术的效果。

重要声明

由于血管的阻塞（再狭窄），由于血管平滑肌细胞的增殖和迁移，用于冠状动脉血运重建的血管外科手术策略显示出很高的失败率。我们先前曾报道过，Kv1.3通道的阻滞剂代表了一种有效的抗再狭窄疗法，但尚未探索其控释的传递系统。在这里，我们测试了多种弹性蛋白像重组蛋白（ELRs）水凝胶在体内和体外以及在人类血管中在各种再狭窄模型中递送Kv1.3阻断剂PAP-1的功效。我们证明了活性化合物和先进的输送方法的结合可以改善患者血管手术的效果。