[Application of internal carotid artery stent in glomus jugular paraganglioma surgery].

Objective:To summarize the application of internal carotid artery stent in glomus jugular paraganglioma surgery, and to provide an effective strategy for reducing the risk of internal carotid artery injury. Methods:This article reviewed the surgical cases of internal carotid artery stent implanting from 2018.06 to 2022.12, and discussed the stent placement method, treatment protocols, and perioperative management strategies. Results:A total of 5 patients underwent a comprehensive evaluation of the degree of internal carotid artery invasion using imaging techniques such as MRI, carotid CT angiography （CTA）, and digital silhouette angiography （DSA）. All patients were found to have varying degrees of internal carotid artery involvement. Stenting of the internal carotid artery was performed in all patients before surgery, and the stenting process went smoothly without any internal carotid artery injury. Three months after stenting, tumor resection or subtotal resection surgery was performed to avoid internal carotid artery injury during the surgery, and the surgical process was successfully completed. Postoperative follow-up from 4 months to 2 years showed that the internal carotid artery was patent after stent placement, with great endothelialization process and no stent-related complications. Conclusion:In patients with glomus jugular paraganglioma, when preoperative imaging shows internal carotid artery involvement, preoperative stenting is a safe and effective therapeutic strategy to reinforce the arterial wall structure, protect and maintain the integrity of the artery, and reduce the risk of vascular injury during the surgery. This article summarizes the experience of internal carotid artery stent in glomus jugular paraganglioma surgery, which provides an important reference for clinical practice.

Neck lump evaluation and pseudoaneurysm.

Pseudoaneurysm is the formation of a sac due to damage in the continuity of the arterial wall. Iatrogenic carotid artery aneurysm is a rare, life-threatening complication following fine needle aspiration (FNA). We are presenting here a case of pseudoaneurysm following FNA with a literature review.

Inositol 1,4,5-Trisphosphate Receptors Regulate Vascular Smooth Muscle Cell Proliferation and Neointima Formation in Mice.

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. METHODS AND 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.

[Treatment strategy of carotid blowout syndrome after radiotherapy for nasopharyngeal carcinoma].

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.

Successful treatment of iatrogenic internal carotid artery pseudoaneurysm following carotid endarterectomy with thrombin injection: a case report.

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. CASE PRESENTATION: 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. CONCLUSION: 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.

Outcomes of penetrating carotid artery injuries: A South African multicentre study.

BACKGROUND: This multicenter study examines the contemporary management of penetrating carotid artery injury (PCAI) to identify trends in management, outcomes, and to determine prognostic factors for stroke and death. METHODS: Data from three large urban trauma centers in South Africa were retrospectively reviewed for patients who presented with PCAI from 2012 to 2020. RESULTS: Of 149 identified patients, 137 actively managed patients were included. Twenty-four patients (17.9%) presented in coma and 12 (9.0%) with localizing signs (LS). CT angiography was performed on admission for 120 (87.6%) patients. Thirty patients (21.9%) underwent nonoperative management, 87 (63.5%) open surgery, and 20 (14.6%) endovascular stenting. Eighteen patients (13.1%) died, and 15 (12.6%) surviving patients had strokes. Ligation was significantly related to death and reperfusion to survival. A mechanism of gunshot wound, occlusive injuries, a threatened airway, a systolic blood pressure <90 mmHg, hard signs of vascular injury, a low GCS, coma, a CT brain demonstrating infarct, a high injury severity score and shock index, a low pH or HCO3, and an elevated lactate were significant independent prognostic factors for death. Ligation was unsurvivable in all patients with severe neurological deficits, whereas reperfusion procedures resulted in survival in 63% (12/19) patients with coma and 78% (7/9) with LS although with high stroke rates (coma: 25.0%, LS: 85.7%). CONCLUSIONS: Outcomes in PCAI, including patients with severe neurological deficit and stroke, are better when reperfused. Reperfusion holds the best promise of survival and ligation should be reserved for technically inaccessible bleeding injuries.

Loss of Smooth Muscle Tenascin-X Inhibits Vascular Remodeling Through Increased TGF-ß Signaling.

BACKGROUND: 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-ß (transforming growth factor-ß) is critical for VSMC differentiation and to counterbalance the effect of dedifferentiating factors. However, the mechanisms controlling TGF-ß 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-ß and to prevent it from activating its receptor. METHODS: 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. RESULTS: 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-ß 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-ß antibody or additional SMC-specific loss of the TGF-ß receptor reverted the effects of SMC-specific TN-X deficiency. CONCLUSIONS: In summary, TN-X critically regulates VSMC plasticity during vascular injury by inhibiting TGF-ß signaling. Our data indicate that inhibition of vascular smooth muscle TN-X may represent a strategy to prevent and treat pathological vascular remodeling.

Targeted mitigation of neointimal hyperplasia via magnetic field-directed localization of superparamagnetic iron oxide nanoparticle-labeled endothelial progenitor cells following carotid balloon catheter injury in rats.

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-ß1 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.

Neointimal hyperplasia after endoluminal injury in mice is dependent on tissue factor- and angiopoietin-2 dependent interferon gamma production by fibrocytes and macrophages.

Background: 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. Methods and results: 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. Conclusion: 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.

Kanglexin counters vascular smooth muscle cell dedifferentiation and associated arteriosclerosis through inhibiting PDGFR.

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. PURPOSE: 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-ß. Mechanism research work proved that KLX prevented VSMC proliferation, migration and dedifferentiation via activating the PDGFR-ß-MEK -ERK-ELK-1/KLF4 signaling pathway. CONCLUSION: 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-ß-MEK-ERK-ELK-1/KLF4 signaling. KLX exhibits promising potential as a viable therapeutic agent for the treatment of VSMC phenotype conversion associated arteriosclerosis.

Linarin Ameliorates Restenosis After Vascular Injury in Type 2 Diabetes Mellitus via Regulating ADAM10-Mediated Notch Signaling Pathway.

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.

Carotid Artery Aneurysm-Induced Mediastinal Hematoma Leading to Airway Compression-A Rare Complication of Internal Jugular Vein Puncture.

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.

Assessing radiation-induced carotid artery injury using ultrasound in patients with head and neck cancer.

BACKGROUND AND PURPOSE: Radiotherapy (RT) can damage neck vessels in patients with head and neck cancer (HNC). This study investigated the early effects of RT on carotid artery, including the internal media thickness (IMT) and carotid plaques of the common carotid artery (CCA). MATERIALS AND METHODS: This study included 69 patients with HNC who underwent RT at the First Hospital of Jilin University from March 2017 to September 2022, and 69 healthy participants as controls. Color Doppler ultrasound (CDUS) of the carotid artery was used to measure the CCA IMT and plaques. RESULTS: Left CCA IMT increased from 0.60 mm (0.60, 0.70) before RT to 0.70 mm (0.60, 1.20) after RT (P < 0.0001). Right CCA IMT changed from 0.60 mm (0.60, 0.71) before RT to 0.60 mm (0.60, 1.10) after RT (P = 0.0002). CCA IMT was 0.60 mm (0.60, 0.70) and 0.80 mm (0.60, 1.20) in the ≤40 Gy and >40 Gy groups (P = 0.0004). The CCA plaques number increased significantly after RT on both the left and right sides (Pleft < 0.0001; Pright <0.0001). The CCA plaques volume increased from 0 mm3 (0, 11.35) and 0 mm3 (0, 8.55) before RT to 8.8 mm3 (0, 21.5) and 5.8 mm3 (0, 16.1) on the left and right sides. Correlation analysis revealed a correlation between CCA IMT and age (r = 0.283, P = 0.001), smoking status (r = 0.179, P = 0.020), and radiation dose (r = 0.188, P = 0.028). CONCLUSION: RT significantly increased CCA IMT, and the growth was related to the radiation dose. The number and volume of the CCA plaques also increased after RT.

The role of number of affected vessels on radiologic and clinical outcomes of patients with blunt cerebrovascular injury.

OBJECTIVE: There is a lack of data on the role of characteristics of injured vessels on the outcomes of patients with blunt cerebrovascular injuries (BCVIs). The aim of this study was to assess the effect of the number (single vs multiple) of injured vessels on outcomes. METHODS: This is a retrospective study at two American College of Surgeons Level I trauma centers (2017-2021). Adult (>16 years) trauma patients with BCVIs are included. Injuries were graded by the Denver Scale based on the initial computed tomography angiography (CTA). Early repeat CTA was performed 7 to 10 days after diagnosis. Patients were stratified by the number (single vs multiple) of the involved vessels. Outcomes included progression of BCVIs on repeat CTA, stroke, and in-hospital mortality attributable to BCVIs. Multivariable regression analyses were performed to identify the association between the number of injured vessels and outcomes. RESULTS: A total of 491 patients with 591 injured vessels (285 carotid and 306 vertebral arteries) were identified. Sixty percent were male, the mean age was 44 years, and the median Injury Severity Score was 18 (interquartile range, 11-25). Overall, 18% had multiple-vessel injuries, 16% had bilateral vessel injuries, and 3% had multiple injuries on the same side. The overall rates of progression to higher-grade injuries, stroke, and mortality were 23%, 7.7%, and 8.8%, respectively. On uni- and multivariable analyses, multiple BCVIs were associated with progression to higher-grade injuries on repeat imaging, stroke, and mortality compared with single-vessel injuries. CONCLUSIONS: BCVIs with multiple injured vessels are more likely to progress to higher grades on repeat CTA, with multiple injuries independently associated with worse clinical outcomes, compared with those with single injuries. These findings highlight the importance of incorporating the number of injured vessels in clinical decision-making and in defining protocols for repeat imaging.

Report on Pseudoaneurysm Caused by Injury of Internal Carotid Artery During Endoscopic Pituitary Surgery and Rebleeding After Treatment With Willis Covered Stent.

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.

KLF13 promotes VSMCs phenotypic dedifferentiation by directly binding to the SM22α promoter.

Krüppel-like factor 13 (KLF13), a zinc finger transcription factor, is considered as a potential regulator of cardiomyocyte differentiation and proliferation during heart morphogenesis. However, its precise role in the dedifferentiation of vascular smooth muscle cells (VSMCs) during atherosclerosis and neointimal formation after injury remains poorly understood. In this study, we investigated the relationship between KLF13 and SM22α expression in normal and atherosclerotic plaques by bioanalysis, and observed a significant increase in KLF13 levels in the atherosclerotic plaques of both human patients and ApoE-/- mice. Knockdown of KLF13 was found to ameliorate intimal hyperplasia following carotid artery injury. Furthermore, we discovered that KLF13 directly binds to the SM22α promoter, leading to the phenotypic dedifferentiation of VSMCs. Remarkably, we observed a significant inhibition of platelet-derived growth factor BB-induced VSMCs dedifferentiation, proliferation, and migration when knocked down KLF13 in VSMCs. This inhibitory effect of KLF13 knockdown on VCMC function was, at least in part, mediated by the inactivation of p-AKT signaling in VSMCs. Overall, our findings shed light on a potential therapeutic target for treating atherosclerotic lesions and restenosis after vascular injury.

Surgical Management and Clinical Outcomes of Extracranial Carotid Artery Pseudoaneurysms.

INTRODUCTION: Extracranial carotid artery (CA) pseudoaneurysms are uncommon and can cause embolic stroke, compressive symptoms, or (rarely) can rupture. It is of paramount importance to treat this entity to avoid life-threatening complications. In this study, the authors described a cohort of patients that required open surgical repair. METHODS: This article reported the authors' experience with open surgical repair of extracranial CA pseudoaneurysms by presenting a retrospective review of data at their institution from 2016 to 2022. RESULTS: Of 8 patients that underwent open repair, 6 were male and 8 were female. The most common etiology was traumatic (penetrating trauma in 4 patients, iatrogenic injury in 2, and blunt trauma in 1) and 1 was infective. All patients presented with a neck mass, and 5 had compressive symptoms. Primary repair was performed in 4 patients, interposition graft using an autologous vein in 2, and patch repair in 2. None of the patients experienced perioperative mortality or stroke; nor did they develop any complications over a median follow-up period of 30 months. CONCLUSION: This report demonstrated that large-size extracranial pseudoaneurysms, whether traumatic or infective etiology, can be safely repaired using an open surgical approach.

Small nucleolar RNA host gene 18 controls vascular smooth muscle cell contractile phenotype and neointimal hyperplasia.

AIMS: Long non-coding RNA (LncRNA) small nucleolar RNA host gene 18 (SNHG18) has been widely implicated in cancers. However, little is known about its functional involvement in vascular diseases. Herein, we attempted to explore a role for SNHG18 in modulating vascular smooth muscle cell (VSMC) contractile phenotype and injury-induced neointima formation. METHODS AND RESULTS: Analysis of single-cell RNA sequencing and transcriptomic datasets showed decreased levels of SNHG18 in injured and atherosclerotic murine and human arteries, which is positively associated with VSMC contractile genes. SNHG18 was upregulated in VSMCs by TGFß1 through transcription factors Sp1 and SMAD3. SNHG18 gene gain/loss-of-function studies revealed that VSMC contractile phenotype was positively regulated by SNHG18. Mechanistic studies showed that SNHG18 promotes a contractile VSMC phenotype by up-regulating miR-22-3p. SNHG18 up-regulates miR-22 biogenesis and miR-22-3p production by competitive binding with the A-to-I RNA editing enzyme, adenosine deaminase acting on RNA-2 (ADAR2). Surprisingly, we observed that ADAR2 inhibited miR-22 biogenesis not through increasing A-to-I editing within primary miR-22, but by interfering with the binding of microprocessor complex subunit DGCR8 to primary miR-22. Importantly, perivascular SNHG18 overexpression in the injured vessels dramatically up-regulated the expression levels of miR-22-3p and VSMC contractile genes, and prevented injury-induced neointimal hyperplasia. Such modulatory effects were reverted by miR-22-3p inhibition in the injured arteries. Finally, we observed a similar regulator role for SNHG18 in human VSMCs and a decreased expression level of both SNHG18 and miR-22-3p in diseased human arteries; and we found that the expression level of SNHG18 was positively associated with that of miR-22-3p in both healthy and diseased human arteries. CONCLUSION: We demonstrate that SNHG18 is a novel regulator in governing VSMC contractile phenotype and preventing injury-induced neointimal hyperplasia. Our findings have important implications for therapeutic targeting snhg18/miR-22-3p signalling in vascular diseases.

Coptisine inhibits neointimal hyperplasia through attenuating Pak1/Pak2 signaling in vascular smooth muscle cells without retardation of re-endothelialization.

BACKGROUND AND AIMS: Vascular injury-induced endothelium-denudation and profound vascular smooth muscle cells (VSMCs) proliferation and dis-regulated apoptosis lead to post-angioplasty restenosis. Coptisine (CTS), an isoquinoline alkaloid, has multiple beneficial effects on the cardiovascular system. Recent studies identified it selectively inhibits VSMCs proliferation. However, its effects on neointimal hyperplasia, re-endothelialization, and the underlying mechanisms are still unclear. METHODS: Cell viability was assayed by 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and cell counting kit-8 (CCK-8). Cell proliferation and apoptosis were measured by flow cytometry and immunofluorescence of Ki67 and TUNEL. Quantitative phosphoproteomics (QPP) was employed to screen CTS-responsive phosphor-sites in the key regulators of cell proliferation and apoptosis. Neointimal hyperplasia was induced by balloon injury of rat left carotid artery (LCA). Adenoviral gene transfer was conducted in both cultured cells and LCA. Re-endothelialization was evaluated by Evan's blue staining of LCA. RESULTS: 1) CTS had strong anti-proliferative and pro-apoptotic effects in cultured rat VSMCs, with the EC50 4∼10-folds lower than that in endothelial cells (ECs). 2) Rats administered with CTS, either locally to LCA's periadventitial space or orally, demonstrated a potently inhibited balloon injury-induced neointimal hyperplasia, but had no delaying effect on re-endothelialization. 3) The QPP results revealed that the phosphorylation levels of Pak1S144/S203, Pak2S20/S197, Erk1T202/Y204, Erk2T185/Y187, and BadS136 were significantly decreased in VSMCs by CTS. 4) Adenoviral expression of phosphomimetic mutants Pak1D144/D203/Pak2D20/D197 enhanced Pak1/2 activities, stimulated the downstream pErk1T202/Y204/pErk2T185/Y187/pErk3S189/pBadS136, attenuated CTS-mediated inhibition of VSMCs proliferation and promotion of apoptosis in vitro, and potentiated neointimal hyperplasia in vivo. 5) Adenoviral expression of phosphoresistant mutants Pak1A144/A203/Pak2A20/A197 inactivated Pak1/2 and totally simulated the inhibitory effects of CTS on platelet-derived growth factor (PDGF)-stimulated VSMCs proliferation and PDGF-inhibited apoptosis in vitro and neointimal hyperplasia in vivo. 6) LCA injury significantly enhanced the endogenous phosphorylation levels of all but pBadS136. CTS markedly attenuated all the enhanced levels. CONCLUSIONS: These results indicate that CTS is a promising medicine for prevention of post-angioplasty restenosis without adverse impact on re-endothelialization. CTS-directed suppression of pPak1S144/S203/pPak2S20/S197 and the subsequent effects on downstream pErk1T202/Y204/pErk2T185/Y187/pErk3S189 and pBadS136 underline its mechanisms of inhibition of VSMCs proliferation and stimulation of apoptosis. Therefore, the phosphor-sites of Pak1S144/S203/Pak2S20/S197 constitute a potential drug-screening target for fighting neointimal hyperplasia restenosis.