BACKGROUND: Vascular smooth muscle cell (VSMC) proliferation is involved in many types of arterial diseases, including neointima hyperplasia, in which Ca2+ has been recognized as a key player. However, the physiological role of Ca2+ release via inositol 1,4,5-trisphosphate receptors (IP3Rs) from endoplasmic reticulum in regulating VSMC proliferation has not been well determined.
RESULTS: Both in vitro cell culture models and in vivo mouse models were generated to investigate the role of IP3Rs in regulating VSMC proliferation. Expression of all 3 IP3R subtypes was increased in cultured VSMCs upon platelet-derived growth factor-BB and FBS stimulation as well as in the left carotid artery undergoing intimal thickening after vascular occlusion. Genetic ablation of all 3 IP3R subtypes abolished endoplasmic reticulum Ca2+ release in cultured VSMCs, significantly reduced cell proliferation induced by platelet-derived growth factor-BB and FBS stimulation, and also decreased cell migration of VSMCs. Furthermore, smooth muscle-specific deletion of all IP3R subtypes in adult mice dramatically attenuated neointima formation induced by left carotid artery ligation, accompanied by significant decreases in cell proliferation and matrix metalloproteinase-9 expression in injured vessels. Mechanistically, IP3R-mediated Ca2+ release may activate cAMP response element-binding protein, a key player in controlling VSMC proliferation, via Ca2+/calmodulin-dependent protein kinase II and Akt. Loss of IP3Rs suppressed cAMP response element-binding protein phosphorylation at Ser133 in both cultured VSMCs and injured vessels, whereas application of Ca2+ permeable ionophore, ionomycin, can reverse cAMP response element-binding protein phosphorylation in IP3R triple knockout VSMCs.
CONCLUSIONS: Our results demonstrated an essential role of IP3R-mediated Ca2+ release from endoplasmic reticulum in regulating cAMP response element-binding protein activation, VSMC proliferation, and neointima formation in mouse arteries.

UNASSIGNED: Vascular smooth muscle cells (VSMCs) are highly plastic. Vessel injury induces a phenotypic transformation from differentiated to dedifferentiated VSMCs, which involves reduced expression of contractile proteins and increased production of extracellular matrix and inflammatory cytokines. This transition plays an important role in several cardiovascular diseases such as atherosclerosis, hypertension, and aortic aneurysm. TGF-β (transforming growth factor-β) is critical for VSMC differentiation and to counterbalance the effect of dedifferentiating factors. However, the mechanisms controlling TGF-β activity and VSMC phenotypic regulation under in vivo conditions are poorly understood. The extracellular matrix protein TN-X (tenascin-X) has recently been shown to bind TGF-β and to prevent it from activating its receptor.
UNASSIGNED: We studied the role of TN-X in VSMCs in various murine disease models using tamoxifen-inducible SMC-specific knockout and adeno-associated virus-mediated knockdown.
UNASSIGNED: In hypertensive and high-fat diet-fed mice, after carotid artery ligation as well as in human aneurysmal aortae, expression of Tnxb, the gene encoding TN-X, was increased in VSMCs. Mice with smooth muscle cell-specific loss of TN-X (SMC-Tnxb-KO) showed increased TGF-β signaling in VSMCs, as well as upregulated expression of VSMC differentiation marker genes during vascular remodeling compared with controls. SMC-specific TN-X deficiency decreased neointima formation after carotid artery ligation and reduced vessel wall thickening during Ang II (angiotensin II)-induced hypertension. SMC-Tnxb-KO mice lacking ApoE showed reduced atherosclerosis and Ang II-induced aneurysm formation under high-fat diet. Adeno-associated virus-mediated SMC-specific expression of short hairpin RNA against Tnxb showed similar beneficial effects. Treatment with an anti-TGF-β antibody or additional SMC-specific loss of the TGF-β receptor reverted the effects of SMC-specific TN-X deficiency.
UNASSIGNED: In summary, TN-X critically regulates VSMC plasticity during vascular injury by inhibiting TGF-β signaling. Our data indicate that inhibition of vascular smooth muscle TN-X may represent a strategy to prevent and treat pathological vascular remodeling.

BACKGROUND: The transplantation of endothelial progenitor cells (EPCs) has been shown to reduce neointimal hyperplasia following arterial injury. However, the efficacy of this approach is hampered by limited homing of EPCs to the injury site. Additionally, the in vivo recruitment and metabolic activity of transplanted EPCs have not been continuously monitored.
METHODS: EPCs were labeled with indocyanine green (ICG)-conjugated superparamagnetic iron oxide nanoparticles (SPIONs) and subjected to external magnetic field targeting to enhance their delivery to a carotid balloon injury (BI) model in Sprague-Dawley rats. Magnetic particle imaging (MPI)/ fluorescence imaging (FLI) multimodal in vivo imaging, 3D MPI/CT imaging and MPI/FLI ex vivo imaging was performed after injury. Carotid arteries were collected and analyzed for pathology and immunofluorescence staining. The paracrine effects were analyzed by enzyme-linked immunosorbent assay.
RESULTS: The application of a magnetic field significantly enhanced the localization and retention of SPIONs@PEG-ICG-EPCs at the site of arterial injury, as evidenced by both in vivo continuous monitoring and ex vivo by observation. This targeted delivery approach effectively inhibited neointimal hyperplasia and increased the presence of CD31-positive cells at the injury site. Moreover, serum levels of SDF-1α, VEGF, IGF-1, and TGF-β1 were significantly elevated, indicating enhanced paracrine activity.
CONCLUSIONS: Our findings demonstrate that external magnetic field-directed delivery of SPIONs@PEG-ICG-EPCs to areas of arterial injury can significantly enhance their therapeutic efficacy. This enhancement is likely mediated through increased paracrine signaling. These results underscore the potential of magnetically guided SPIONs@PEG-ICG-EPCs delivery as a promising strategy for treating arterial injuries.

UNASSIGNED: The intimal hyperplasia (IH) and vascular remodelling that follows endovascular injury, for instance after post-angioplasty re-stenosis, results in downstream ischaemia and progressive end organ damage. Interferon gamma (IFNγ) is known to play a critical role in this process. In mouse models we have previously shown that fibrocytes expressing tissue factor (TF) are recruited early to the site of injury. Through thrombin generation and protease activated receptor-1 (PAR-1) activation, fibrocytes secrete angiopoietin-2, stimulate neointimal cell proliferation, inhibit apoptosis and induce CXCL-12 production, all of which contribute to the progressive IH that then develops. In this study we investigated the relationship between TF, angiopoietin-2 and IFNγ.
UNASSIGNED: IH developing in carotid arteries of wild-type mice 4 weeks after endoluminal injury contained a significant proportion of IFNγ+ fibrocytes and macrophages, which we show, using a previously defined adoptive transfer model, were derived from circulating CD34+ cells. IH did not develop after injury in IFNγ-deficient mice, except after transplantation of WT bone marrow or adoptive transfer of WT CD34+ cells. In vitro, CD34+ cells isolated from post-injury mice did not express IFNγ, but this was induced when provided with FVIIa and FX, and enhanced when prothrombin was also provided: In both cases IFNγ secretion was TF-dependent and mediated mainly through protease activated PAR-1. IFNγ was predominantly expressed by fibrocytes. In vivo, all IFNγ+ neointimal cells in WT mice co-expressed angiopoietin-2, as did the small numbers of neointimal cells recruited in IFNγ-/- mice. Adoptively transferred WT CD34+ cells treated with either an anti-TIE-2 antibody, or with siRNA against angiopoetin-2 inhibited the expression of IFNγ and the development of IH.
UNASSIGNED: TF-dependent angiopoietin-2 production by newly recruited fibrocytes, and to a lesser extent macrophages, switches on IFNγ expression, and this is necessary for the IH to develop. These novel findings enhance our understanding of the pathophysiology of IH and expose potential targets for therapeutic intervention.

BACKGROUND: Iatrogenic pseudoaneurysms arising from the internal carotid artery subsequent to carotid endarterectomy are exceptionally infrequent. Herein, we present a case detailing an internal carotid artery pseudoaneurysm that manifested subsequent to a hybrid carotid endarterectomy and endovascular therapy intervention. Our approach to managing this condition involved a novel technique wherein thrombin was directly injected into the luminal cavity of the pseudoaneurysm under the guidance of a C-arm.
METHODS: A 66-year-old male patient of Chinese ethnicity exhibited a 4-month history of headache and a 20-day history of gait disturbance. Digital subtraction angiography revealed occlusion in the cervical region of the left carotid artery. Following a hybrid surgical procedure, the patient reported mild pain and bruising surrounding the incision site of the left internal carotid artery endarterectomy. Subsequent angiography identified the presence of a carotid artery pseudoaneurysm. Utilizing C-arm guidance, thrombin was then directly injected into the luminal cavity of the pseudoaneurysm, resulting in complete healing during follow-up.
CONCLUSIONS: For the management of pseudoaneurysms arising post carotid endarterectomy, the direct injection of thrombin into the aneurysm cavity under the guidance of a C-arm is deemed both safe and efficacious.

Objective:To investigate the treatment of internal carotid artery rupture after radiotherapy for nasopharyngeal carcinoma. Methods:The clinical data of 7 patients with internal carotid artery rupture after radiotherapy for nasopharyngeal carcinoma from March 2020 to March 2023 were retrospectively analyzed. Results:Skull base osteonecrosis with infection occurred in 4 cases, and tumor recurrence with infection in 3 cases. DSA showed that internal carotid artery rupture was located in the internal carotid artery petrosal segment in 6 cases, and in the paravicular segment in 1 case. Balloon occlusion test（BOT） was performed in 6 patients, of which 3 passed and 3 failed. Vascular treatment included internal carotid artery embolization（4 cases）, false aneurysm embolization 1 case（rebleeding）, coated stent 1 case（rebleeding）, muscle compression during operation（1 case）. Patients with rebleeding received high-flow bypass. Three cases developed cerebral infarction after embolization without severe sequelae after treatment, and no death occurred within 90 days. After bleeding control, all 3 patients with cranial base necrosis received surgical treatment to remove the necrotic bone and tissue flap repair, and 1 patient with recurrence received gamma knife and targeted therapy, 1 patient received immune and surgical therapy, and 1 patient received immune and targeted therapy. Conclusion:Rupture and hemorrhage of internal carotid artery after radiotherapy is related to tumor invasion, tissue injury and local infection after radiotherapy. For those caused by tumor invasion, it is recommended to sacrifice the responsible vessels. For those caused by infection, emergency surgery is recommended and blood vessels preserved. Emergency vascular occlusion remains a life-saving option.
目的：探讨鼻咽癌放疗后颈内动脉破裂的治疗策略。 方法：回顾性分析2020年3月—2023年3月收治的7例鼻咽癌放疗后颈内动脉破裂出血患者的临床资料。 结果：7例患者中4例发生颅底骨坏死伴感染，3例肿瘤复发伴感染。DSA造影提示6例颈内动脉破裂位于颈内动脉岩骨段，1例位于斜坡旁段。6例患者行球囊闭塞试验（BOT），通过3例，未通过3例。血管治疗方案：颈内动脉长程栓塞4例，假性动脉瘤栓塞1例（再出血），覆膜支架1例（再出血），手术中肌肉压迫1例，再出血的患者行高流量搭桥。栓塞后脑梗死3例，经过治疗无后遗症，90 d内无死亡患者。出血控制后3例颅底坏死感染者均行手术治疗清除坏死骨质，并组织瓣修复，1例复发患者行伽马刀及靶向治疗，1例行免疫及手术治疗，1例免疫及靶向治疗。 结论：鼻咽癌放疗后颈内动脉爆裂与肿瘤侵犯和放疗后的损伤和局部组织感染密切相关。对于肿瘤侵犯导致的，建议牺牲责任血管；对于感染造成的破裂出血，建议保留血管，并尽早手术。紧急血管闭塞仍是挽救生命的选择。.

BACKGROUND: Dysregulation of vascular smooth muscle cell (VSMC) function leads to a variety of diseases such as atherosclerosis and hyperplasia after injury. However, antiproliferative drug targeting VSMC exhibits poor specificity. Therefore, there is an urgent to develop highly specific antiproliferative drugs to prevention and treatment VSMC dedifferentiation associated arteriosclerosis. Kanglexin (KLX), a new anthraquinone compound designed by our team, has potential to regulate VSMC phenotype according to the physicochemical properties.
OBJECTIVE: This project aims to evaluate the therapeutic role of KLX in VSMC dedifferentiation and atherosclerosis, neointimal formation and illustrates the underlying molecular mechanism.
METHODS: In vivo, the ApoE-/- mice were fed with high-fat diet (HFD) for a duration of 13 weeks to establish the atherosclerotic model. And rat carotid artery injury model was performed to establish the neointimal formation model. In vitro, PDGF-BB was used to induce VSMC dedifferentiation.
RESULTS: We found that KLX ameliorated the atherosclerotic progression including atherosclerotic lesion formation, lipid deposition and collagen deposition in aorta and aortic sinus in atherosclerotic mouse model. In addition, The administration of KLX effectively ameliorated neointimal formation in the carotid artery following balloon injury in SD rats. The findings derived from molecular docking and surface plasmon resonance (SPR) experiments unequivocally demonstrate that KLX had potential to bind PDGFR-β. Mechanism research work proved that KLX prevented VSMC proliferation, migration and dedifferentiation via activating the PDGFR-β-MEK -ERK-ELK-1/KLF4 signaling pathway.
CONCLUSIONS: Collectively, we demonstrated that KLX effectively attenuated the progression of atherosclerosis in ApoE-/- mice and carotid arterial neointimal formation in SD rats by inhibiting VSMC phenotypic conversion via PDGFR-β-MEK-ERK-ELK-1/KLF4 signaling. KLX exhibits promising potential as a viable therapeutic agent for the treatment of VSMC phenotype conversion associated arteriosclerosis.

Vascular lesions frequently arise as complication in patients diagnosed with diabetes mellitus (DM). Presently, percutaneous coronary intervention (PCI) and antithrombotic therapy serve as primary treatments. However, in-stent restenosis persists as a challenging clinical issue following PCI, lacking sustained and effective treatment. Linarin (LN) exhibits diverse pharmacological activities and is regarded as a potential drug for treating various diseases, including DM. But its specific role in restenosis after vascular injury in DM patients remains unclear. A rat model of diabetes-related restenosis was established to evaluate the role of LN on neointimal hyperplasia. Vascular smooth muscle cells (VSMCs) stimulated by high glucose (HG, 30 mM) underwent LN treatment. Additionally, an overexpression plasmid of A disintegrin and metalloproteinases (ADAM10) was constructed to transfect VSMCs. We employed CCK-8, Brdu, wound-healing scratch, and transwell migration assays to evaluate the proliferation and migration of VSMCs. Furthermore, western blot and immunofluorescence assays were utilized to investigate the expressions of ADAM10 and the downstream Notch signaling pathway in vivo and in vitro models. LN notably alleviated intimal hyperplasia after vascular injury in DM rats and reduced the protein expression of ADAM10, alongside its downstream Notch1 signaling pathway-related proteins (Notch1, NICD and Hes1) in rat carotid artery tissues. LN effectively suppressed the proliferation and migration of VSMCs induced by HG, downregulating the protein expression of ADAM10, Notch1, NICD and Hes1. Moreover, our findings indicated that ADAM10 overexpression significantly reversed LN\'s effects on proliferation, migration, and the expression of Notch1 signaling pathway-related proteins in HG-treated VSMCs. LN demonstrates potential therapeutic efficacy in addressing restenosis after diabetic-related vascular injury, with the ADAM10 mediated Notch signaling pathway playing a pivotal role.

OBJECTIVE: Report on a case of pseudoaneurysm which was caused by injury of the internal carotid artery (ICA) during endoscopic endonasal surgery (EES), which was followed by rebleeding after treatment with a Willis covered stent.
METHODS: A woman, aged 68, underwent EES for the treatment of a pituitary adenoma. During the surgery, the right ICA was injured, and successfully hemostasis by packed with cottonoid and gelatin sponge. Besides, cerebral angiography was performed in the interventional operating room for the purpose of discovering the formation of a pseudoaneurysm in the cavernous sinus segment of ICA, which was treated with a covered stent. After successfully placing the covered stent, the patient was promptly transferred to the general operating room for the removal of the cottonoid and to address the bleeding once again. The authors employ crushed muscles and cottonoid to locally compress and stop bleeding. Owing to concerns about the risk of rebleeding in the patient, after stent implantation, the patient did not utilize antiplatelet drugs. After the surgery, the patient developed occlusion of the right ICA and massive cerebral infarction in the right hemisphere. Dehydration, anti-infection, rehabilitation, hyperbaric oxygen, as well as related treatments, were given. The cottonoid was removed in EES 2 months postsurgery, and no instances of bleeding were observed. Six months after surgery, the patient had clear consciousness and hemiplegia in the left limb, with a Glasgow Outcome Scale score of 4.
RESULTS: The ICA was injured during EES, which resulted in the formation of a pseudoaneurysm, the Willis stent was adopted for treatment, and there was a risk of rebleeding after the nasal packing (cottonoid, crushed muscles) was removed immediately.
CONCLUSIONS: The ICA was injured during EES after bleeding was controlled by packing with cottonoid, crushed muscles, etc, subsequently, the patient was given intravascular treatment, it is advised to make thorough preparations and, after a suitable period, remove nasal packing in the hybrid operating room to address unexpected situations and unforeseen circumstances.

Carotid artery puncture is a common complication of internal jugular vein (IJV) catheterization. However, there are few reports about an aneurysm from the carotid artery that can develop into an occult mediastinal hematoma, leading to airway compression. In this case study, we present the case of a 71-year-old male who experienced an aneurysm and delayed mediastinal hematoma, ultimately resulting in airway compression after right jugular line insertion. Our findings highlight the importance of not only addressing local hematoma formation at the puncture site promptly, but also recognizing the potential for aneurysm extension into the mediastinum and the formation of an occult hematoma, which can lead to airway compression. Additionally, we provide a summary of landmark technique precautions that can help reduce the occurrence of such severe complications.