Carotid and vertebral artery stenosis is a common clinical lesion and is caused by atherosclerosis in approximately 95% of patients. Surgical treatment of carotid stenosis includes traditional atherosclerotic plaque resection and minimally invasive endovascular angioplasty. Whether stenting can replace traditional surgery will depend on its safety and restenosis after stent implantation. Clinical results of large-scale stenting of carotid artery stenosis show that the restenosis rates at 6 and 12 months are 1.99% and 3.46%, respectively. This article presents a comprehensive overview of recent research advances in the mechanism and treatment of restenosis after endovascular stenting. The development of restenosis is the result of a homeostatic imbalance in the repair process after intimal injury. The essence of restenosis is the healing response after arterial injury, which is a complex biological process mediated by a series of vasoactive substances and growth factors. Vessel smooth muscle cell (VSMC) migration, proliferation and secretion are three important aspects of intimal proliferation, of which endothelial cell injury is the initiating factor of restenosis, and the balance between intimal proliferation and vascular remodeling determines the extent of restenosis. (a) Vascular smooth muscle cell overproliferation Endothelial cell injury, shedding, and basement membrane exposure cause platelet aggregation, and together with the injured endothelial cells, they secrete platelet-derived growth factor (PDGF), fibroblast growth factor (hFGF), and insulin-like growth factor (IGF), which act on the respective receptors on VSMC at the injury site through multiple pathways to cause The reduction of VSMC apoptosis is also involved in this process. (b) Activation of coagulation mechanism leads to local thrombosis mainly due to the injury of endothelial cells by angioplasty, resulting in tearing of the intima, exposure of the intima, release of various vasoactive molecules, promotion of vasoconstriction, and promotion of platelet adhesion in the injured area, secretion of coagulation factors, activation of thrombin and thus promotion of local thrombosis, which usually occurs within 24 hours after endovascular stenting. It usually occurs within 24 hours after endovascular stenting, and thrombus mechanization is one of the causes of restenosis. In addition, endothelial cell injury can produce inflammatory factors such as monocyte chemokines, which promote the adhesion and infiltration of inflammatory cells and cause local inflammatory reactions. (iii) Vascular remodeling Studies have shown that early VSMC hyperplasia after angioplasty often occurs within 2 weeks after surgery, but endothelial thickening persists until 12 weeks, so vascular remodeling plays an important role in the development of restenosis. Vascular remodeling is a physiological process of vascular repair, and remodeling results in changes in total vascular volume, particularly within the endoelastic plate. Extracellular matrix (ECM) plays a major role in the process of revascularization. Besides supporting and connecting tissue cells, it is also involved in complex signal transduction and functional regulatory roles, mainly on VSMC. In addition, local hemodynamic changes occur after stenting, manifested as local vascular shear force is significantly lower than the preoperative level, and the organism itself appears to retract the local vessel wall. Second, the prevention and control of restenosis In response to the above-mentioned factors for the occurrence of restenosis, corresponding prevention and control methods have been generated. Because the initiating factor of restenosis after stent implantation is endothelial and intimal damage, preventing or reducing intimal damage is the first measure to be adopted, such as not blocking the vessel for too long, maintaining continuous drip during operation, using balloons to remove emboli if necessary, choosing stents of suitable length and diameter, and performing pre-expansion and post-expansion if necessary, and striving for “no damage” or “less damage”. The operation should be “non-invasive” or “less-invasive”. Other methods include: gene therapy, stent modification, radiation therapy, drug therapy, etc. (i) Gene therapy All restenosis processes are potential targets for molecular therapy, and the main strategy is to modify the target cells D endothelial cells to express specific genes to play a role in inhibiting restenosis. The main molecular targets are cellular suicide genes (TK and CD genes), cell cycle regulatory genes (CDK inhibitors P21, P27, P53), anti-thrombotic genes (tissue fibrinogen activator, anti-platelet 2a/2b factor), genes that increase nitric oxide synthesis (e.g. NO synthase genes), cytokines that inhibit smooth muscle cell proliferation, vascular endothelial cell growth factor, antisense basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), antisense nucleic acid genes that inhibit vascular smooth muscle proliferation. Others, such as antioxidant HMG CoA inhibitors, reduce extracellular matrix, while integrins, vasodilator genes and fibroblast growth factor genes (FGF), act on multiple aspects of restenosis formation (including endothelial proliferation and vascular remodeling) with multiple biological effects, while amplifying their biological effects with paracrine mechanisms. Recent studies have used local injections at the site of vascular injury to introduce the superoxide dismutase EC-SOD gene into vascular endothelial cells outside the stent, which can secrete SOD and exhibit anti-stenosis effects through antioxidant effects. The expression of activating PKG mediated by adenovirus can reduce the formation of neovascularization and decrease the occurrence of restenosis. cGMP is mainly involved in apoptosis and relaxation of vascular smooth muscle through the PKG pathway, and reduces cell proliferation and migration. The construction of a new generation of adenovirus to improve its targeting, while reducing the immunogenicity and toxicity of the virus, improving the efficiency of gene transfer, screening more appropriate target genes, and using multi-gene multi-linked combined gene therapy is its direction, and it is believed that gene therapy to prevent restenosis into the clinic and achieve significant efficacy will become possible. (B) Endovascular radiation therapy Some studies have shown that the risk of arterial restenosis at 5 years is significantly lower when endovascular brachytherapy is used during angioplasty than when no radiation therapy is performed, and the effect can last for more than 5 years. The irradiation method generally uses γ and β radiation for external irradiation and intracavitary irradiation. It is generally accepted that the clinical efficacy of 15Gy-20Gy irradiation dose is more certain. Experimental and clinical follow-up observations have shown that radiotherapy can have certain side effects, such as thrombosis, telangiectasia, delayed endothelialization and aneurysm. Popma et al. concluded that beta radiation has the advantages of shorter irradiation time, less exposure, less operator damage and higher attenuation rate in the tissue compared to gamma radiation. It is believed that the main mechanisms of restenosis inhibition by radiotherapy are: inhibition of VSMC migration, induction of G1 phase block and consequent inhibition of VSMC proliferation. On the other hand, radiotherapy affects arterial remodeling, which is mainly manifested by the inhibition of proliferation of mesangial and epicardial smooth muscle cells by radiotherapy. The role of apoptosis in this process is uncertain. The inhibitory effect of radiation on macrophages is the main mechanism by which radiation inhibits VSMC. Similarly radiation therapy results in a decrease in collagen fibril and extracellular matrix content, smaller atheromatous plaques, and thinning of the mesothelium favoring vascular remodeling and inhibition of late vasoconstriction. (iii) Photodynamic therapy In recent years, the application of laser and UV intraluminal local irradiation to prevent restenosis has attracted the attention of clinical workers. The use of intravascular kinetic therapy can prevent endothelial proliferation and vascular remodeling after angioplasty. One study investigated the effect of ultrasound kinetic therapy on de novo endothelial hyperplasia after stent placement using the new sensitizer PAD-S31, and the results showed that PAD combined with ultrasound treatment significantly inhibited vascular de novo endothelial hypertrophy. PDT was shown to inhibit injurious restenosis without secondary inflammation and to promote endothelial regeneration. The mechanism of action is threefold: 1 administration of a certain dose of photosensitizer, activated by irradiation, transmits energy to molecular oxygen to produce singlet oxygen, releasing a large number of free radicals to damage cellular DNA, enzymes and protein structure and function, resulting in destruction of VSMC lysosomal enzymes leading to apoptosis, which in turn inhibits VSMC proliferation; 2 PDT can act on the extracellular matrix and inhibit VSMC migration; 3 PDT can cause collagen fiber cross-linking, which attenuates vascular retraction in the late stage of vascular remodeling. (iv) Ultrasound therapy Ultrasound under certain conditions can inhibit proliferating cells, which provides a new way to prevent restenosis after stent implantation. It has been shown that ultrasound can inhibit the adhesion, migration and proliferation of vascular smooth muscle, thus interfering with the repair process of injured vessels and preventing excessive proliferation of smooth muscle cells. One study used 700 KHz ultrasound to intravascularly irradiate porcine vessels after stent implantation and found that ultrasound significantly inhibited smooth muscle and intimal proliferation. However, tissues exhibit complexity and duality to different conditions of ultrasound. Most low-intensity, low-frequency ultrasound increases the synthesis of colloidal and non-colloidal proteins, while only stronger ultrasound can inhibit their synthesis; different ultrasound parameters have different effects on the synthesis and secretion of extracellular matrix, and in addition cells in different cell cycles have significant differences in sensitivity to ultrasound, and the search for appropriate ultrasound parameters will become an The search for appropriate ultrasound parameters will be an important goal. (V) Special stents 1. Stent restenosis after stent implantation is closely related to the stent, and the consistency of the stent site and the stenosis site makes the modification and modification of the stent the most concise and effective method. Recently, drug-coated stents have become a hot topic. The stent is based on a local drug release system, where a drug is physically dissolved in a matrix to cover the stent uniformly with a multimer and is slowly released into the tissue adjacent to the stent. Cimorrolimus, which has been used to inhibit renal graft rejection, effectively blocks the cell cycle and inhibits cellular hyperproliferation. By coating the stent surface with cimorrolimus, studies have shown a significantly lower 6-month restenosis rate (0%) for drug-coated stents compared to the standard stent group (26.6%) . Results for rapamycin, another immunosuppressant, showed restenosis rates of 8.9% and 36.3% for the drug stent versus the normal stent, and its inhibition of endothelial proliferation was durable at 2-year follow-up. Other drug stents, such as immunosuppressive agents, antineoplastic agents, 17-estradiol, and vascular endothelial growth factor-modified stents are under investigation. The main shortcomings of drug-coated stents are the potential systemic and local cytotoxicity, especially when stents are placed together or overlapping, or the delayed inflammatory response caused by the stent itself, which will cause delayed restenosis with damage to the vascular bed, other side effects are thrombosis and aneurysm formation. 2.Radioactive vascular stenting Radioactive vascular stenting is an emerging research direction, which is based on the role of intravascular brachytherapy on restenosis, its advantages include: it requires low activity, easy to protect, easy to operate, safe and convenient for clinical use, the main disadvantage is that the stents are skeletonized structure, the irradiation dose is not uniform, and at the same time there are stent “edge The main disadvantage is that the stents are skeletonized, the irradiation dose is not uniform, and there is a problem of “edge” restenosis. Nuclides include 55Co, 32P, 198Au and 103Pd, etc. From the results of current clinical trials, 32P radioactive stent can significantly reduce in-stent restenosis, and there is a dose-D-dependent relationship in the range of 27.7KBq for reducing neointimal hyperplasia in the stent, in which the inhibition of neutrophil activation may be one of the main mechanisms of radioactive stent to prevent restenosis. In addition, radioactive stents can inhibit neointimal formation by inhibiting or damaging the proliferation of vascular smooth muscle cells, and some studies suggest that radioactive stents can establish an electronic barrier after placement into the vessel and inhibit the migration of smooth muscle cells from the myocardium to the intima. 3.Magnetized stent Based on the magnetic field treatment can dilate the blood vessels and reduce the inflammatory response of the endothelium, magnetized endovascular stent has been developed, and the effective magnetic field strength of magnetized stent can last for more than 1~2 years. The mechanism of the inhibition of VSMC proliferation by magnetic field may be: 1 the effect of magnetic field on cell metabolism, the activity or function of enzymes required for cell metabolism is disturbed, the level of cell metabolism is reduced, and the cell proliferation ability is reduced; 2 the effect of magnetic field on cellular DNA synthesis cycle, the energy of magnetic field acts directly on the messenger transcription system of DNA synthesis, which reduces the rate of DNA synthesis and makes VSMC proliferation is inhibited]. It is believed that with the development of new material stents, stents with better performance in all aspects, such as biodegradable stents and vascular stents with dilatation properties, will be more widely used. In addition, drug therapy also plays an important role in the treatment of restenosis, including antiplatelet aggregation drugs, calcium antagonists, angiotensin-converting enzyme inhibitors, and traditional Chinese medicine.