Department of Vascular Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China.
Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
J Cardiovasc Transl Res. 2023 Oct;16(5):1021-1031. doi: 10.1007/s12265-023-10384-8. Epub 2023 Apr 25.
Vascular smooth muscle cells (VSMCs) are involved in restenosis of bypass grafts and cause artery graft occlusion. This study aimed to explore the role of Slit2 in phenotypic switching of VSMCs and its effect on restenosis of vascular conduits. An animal model of vascular graft restenosis (VGR) was produced in SD rats and assessed by echocardiography. The expression of Slit2 and Hif-1α was measured in vivo and in vitro. After Slit2 overexpression, the migration and proliferation of VSMCs were detected in vitro, and the restenosis rates and phenotype of VSMCs were tested in vivo. The arteries of the VGR model presented significant stenosis, and Slit2 was decreased in VSMCs of the VGR model. In vitro, Slit2 overexpression inhibited the migration and proliferation of VSMCs, but Slit2 knockdown promoted migration and proliferation. Hypoxia induced Hif-1α but reduced Slit2, and Hif-1α negatively regulated Slit2 expression. Moreover, Slit2 overexpression weakened the rate of VGR and maintained the patency of artery bypass grafts, which suppressed the phenotypic switching of VSMCs. Slit2 inhibited the synthetic phenotype transformation to inhibit the migration and proliferation of VSMCs and delayed the VGR via Hif-1α.
血管平滑肌细胞（VSMCs）参与旁路移植物再狭窄并导致动脉移植物闭塞。本研究旨在探讨 Slit2 在 VSMCs 表型转化中的作用及其对血管移植物再狭窄的影响。通过超声心动图在 SD 大鼠中产生血管移植物再狭窄（VGR）动物模型，并进行评估。在体内和体外测量 Slit2 和 Hif-1α 的表达。Slit2 过表达后，检测体外 VSMCs 的迁移和增殖，以及体内 VSMCs 的再狭窄率和表型。VGR 模型的动脉出现明显狭窄，VGR 模型中 VSMCs 的 Slit2 减少。体外，Slit2 过表达抑制 VSMCs 的迁移和增殖，但 Slit2 敲低促进迁移和增殖。缺氧诱导 Hif-1α 但降低 Slit2，Hif-1α 负调控 Slit2 表达。此外，Slit2 过表达减弱了 VGR 的速率并维持了旁路移植物的通畅，从而抑制了 VSMCs 的表型转换。Slit2 通过 Hif-1α 抑制合成表型转化，抑制 VSMCs 的迁移和增殖，从而延缓 VGR。
