Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Neurosurgical Institute of Fudan University, Shanghai, China.
J Nanobiotechnology. 2021 Apr 29;19(1):123. doi: 10.1186/s12951-021-00867-8.
An endovascular covered-stent has unique advantages in treating complex intracranial aneurysms; however, in-stent stenosis and late thrombosis have become the main factors affecting the efficacy of covered-stent treatment. Smooth-muscle-cell phenotypic modulation plays an important role in late in-stent stenosis and thrombosis. Here, we determined the efficacy of using covered stents loaded with drugs to inhibit smooth-muscle-cell phenotypic modulation and potentially lower the incidence of long-term complications.
Nanofiber-covered stents were prepared using coaxial electrospinning, with the core solution prepared with 15% heparin and 20 µM rosuvastatin solution (400: 100 µL), and the shell solution prepared with 120 mg/mL hexafluoroisopropanol. We established a rabbit carotid-artery aneurysm model, which was treated with covered stents. Angiography and histology were performed to evaluate the therapeutic efficacy and incidence rate of in-stent stenosis and thrombosis. Phenotype, function, and inflammatory factors of smooth-muscle cells were studied to explore the mechanism of rosuvastatin action in smooth-muscle cells.
Heparin-rosuvastatin-loaded nanofiber scaffold mats inhibited the proliferation of synthetic smooth-muscle cells, and the nanofiber-covered stent effectively treated aneurysms in the absence of notable in-stent stenosis. Additionally, in vitro experiments showed that rosuvastatin inhibited the smooth-muscle-cell phenotypic modulation of platelet-derived growth factor-BB induction and decreased synthetic smooth-muscle-cell viability, as well as secretion of inflammatory cytokines.
Rosuvastatin inhibited the abnormal proliferation of synthetic smooth-muscle cells, and heparin-rosuvastatin-loaded covered stents reduced the incidence of stenosis and late thrombosis, thereby improving the healing rates of stents used for aneurysm treatment.
血管内覆膜支架在治疗复杂颅内动脉瘤方面具有独特优势；然而，支架内狭窄和晚期血栓形成已成为影响覆膜支架治疗效果的主要因素。平滑肌细胞表型调节在晚期支架内狭窄和血栓形成中起着重要作用。在这里，我们确定了使用载药覆膜支架抑制平滑肌细胞表型调节并降低长期并发症发生率的疗效。
采用同轴电纺法制备纳米纤维覆膜支架，芯溶液由 15%肝素和 20µM 瑞舒伐他汀溶液（400:100µL）组成，壳溶液由 120mg/mL 六氟异丙醇组成。我们建立了兔颈动脉动脉瘤模型，并用覆膜支架进行治疗。通过血管造影和组织学评估来评估治疗效果以及支架内狭窄和血栓形成的发生率。研究平滑肌细胞的表型、功能和炎症因子，以探讨瑞舒伐他汀在平滑肌细胞中的作用机制。
肝素-瑞舒伐他汀载药纳米纤维支架抑制合成型平滑肌细胞的增殖，且纳米纤维覆膜支架在无明显支架内狭窄的情况下有效治疗动脉瘤。此外，体外实验表明，瑞舒伐他汀抑制血小板衍生生长因子-BB 诱导的平滑肌细胞表型调节，降低合成型平滑肌细胞活力和炎性细胞因子的分泌。
瑞舒伐他汀抑制合成型平滑肌细胞的异常增殖，肝素-瑞舒伐他汀载药覆膜支架降低狭窄和晚期血栓形成的发生率，从而提高用于治疗动脉瘤的支架的愈合率。
