Lin28a up‐regulation is associated with the formation of restenosis via promoting proliferation and migration of vascular smooth muscle cells

Abstract

To explore the potential role of Lin28a in the development of restenosis after percutaneous transluminal angioplasty, double‐balloon injury surgery and mono‐balloon injury surgery were used to establish restenosis and atherosclerosis models, respectively, so as to better distinguish restenosis from atherosclerotic lesions. Immunohistochemical analysis revealed that significantly higher expression of Lin28a was observed in the iliac arteries of restenosis plaques than that of atherosclerosis plaques. Immunofluorescence studies showed the colocalization of Lin28a with α‐smooth muscle actin in restenosis plaques, rather than in atherosclerosis plaques, which suggested that Lin28a might be related to the unique behaviour of vascular smooth muscle cells (VSMCs) in restenosis. To further confirm above hypothesis, Lin28a expression was up‐regulated by transfection of Lenti‐Lin28a and inhibited by Lenti‐Lin28a‐shRNA transfection in cultured VSMCs, and then the proliferation and migration capability of VSMCs were detected by EdU and Transwell assays, respectively. Results showed that the proliferation and migration of VSMCs were significantly increased in accordance with the up‐regulation of Lin28a expression, while above behaviours of VSMCs were significantly suppressed after inhibiting the expression of Lin28a. In conclusion, the up‐regulation of Lin28a exerts its modulatory effect on VSMCs’ proliferation and migration, which may play a critical role in contributing to pathological formation of restenosis.

GRIA2/ENPP3 Regulates the Proliferation and Migration of Vascular Smooth Muscle Cells in the Restenosis Process Post-PTA in Lower Extremity Arteries

“…In present study, we used a double-balloon injury animal model, which consisted of two steps injuries: the first balloon injury was to induce atherosclerosis plaques and, after the plaques were established, the second balloon injury was performed in the same place to mimic the condition of PTA. We found the plaques developed after the two steps injuries are typically hyperplasia foci of VSMCs and extracellular matrix, which is more closely to human restenosis pathology than simple balloon injury protocol (Strauss et al, 1996;Zhou et al, 2016;Zou et al, 2020).…”

“…Then, a color Doppler ultrasonogram was used to examine the formation of the stenosed iliac arteries after PTA. For the atherosclerosis group, rats received a sham surgery on the same day as the first surgical injury in the restenosis group, and balloon-induced injuries of the iliac arteries were performed to develop models of atherosclerosis after 4 weeks (Zhou et al, 2015(Zhou et al, , 2016Zou et al, 2020).…”

Preparation of ROS‐Responsive Exosome Coating of Nitinol Material for Making the Neurointerventional Stent

“…In this study, endothelial cell immunofluorescence showed that vWF expression in the SMEN group was downregulated compared with that in the BN group, and VE‐cadherin was relatively upregulated, which was beneficial to maintain the integrity of the vascular endothelial cell barrier and reduce platelet adhesion. [ 30,31,58,59 ] Hence, these results suggested that the ROS‐responsive exosome coating could promote the proliferation and migration of endothelial cells and positively affect the endothelialization of NiTi alloy surfaces.…”

Effect of down-regulation of let-7c/g on triggering a double-negative feedback loop and promoting restenosis

“…In the RS group, RS plaques in the right iliac artery were induced by a "two-step injury protocol" [ 16 ] [Supplementary Figure 1, http://links.lww.com/CM9/B619 ]. First, a 1.5-mm, wire-guided balloon catheter (Medtronic, Minnesota, USA) was inserted into the iliac artery through the femoral artery, which was followed by inflation and hauling from the iliac artery to the femoral artery to induce endothelial damage.…”

“…In AS, VSMCs behave appropriately, stabilizing the plaque. [ 14 15 16 ] In contrast, the "malignant" behavior of VSMCs is the main feature of RS, and it leads to rapid obstruction of the already atherosclerotic vessel after treatment. The speedy formation of RS plaques formed the background and foundation of our research, since focusing on the differences between RS and AS may provide a more effective route to identify the specific protein targets of RS and reveal the molecular mechanisms underlying the excessive migration and proliferation of VSMCs after PTA.…”