Histological Features of In-Stent Restenosis after Iliac Vein Thrombus Removal and Stent Placement in a Goat Model.

PURPOSE: To establish an animal model for in-stent restenosis (ISR) after postthrombotic iliac vein stent placement and characterize histopathological changes in tissue within the stented vein. MATERIALS AND METHODS: Iliac vein thrombosis was induced using balloon occlusion and thrombin injection in 8 male Boer goats. Mechanical thrombectomy and iliac vein stent placement were performed 3 days after thrombosis induction. Restenosis was evaluated by venography and optical coherence tomography (OCT) at 1 and 8 weeks after stent placement, and stent specimens were taken for pathological examination after the animals were euthanized. RESULTS: Thrombosis induction was successful in all 8 goats, with >80% iliac vein occlusion. After thrombus removal, OCT revealed considerable venous intimal thickening and a small number of mural thrombi. Neointimal hyperplasia with thrombus formation was observed in all goats 1 week after stent implantation; the degree of ISR was 15%-33%. At 8 weeks, the degree of ISR was 21%-32% in 3 goats, and stent occlusion was observed in 1 goat. At 1 week, the neointima predominantly consisted of fresh thrombi. At 8 weeks, proliferplastic fibrotic tissue and smooth muscle cells (SMCs) were predominant, and the stent surfaces were endothelialized in 2 of 3 goats and partially endothelialized in 1 goat. CONCLUSIONS: In the goat model, postthrombotic neointimal hyperplasia in the venous stent may result from time-dependent thrombus formation and organization, accompanied by migration and proliferation of SMCs, causing ISR. These results provide a basis to further explore the mechanism of venous ISR and promote the development of venous stents that reduce neointimal hyperplasia.

Single-Stage Endovascular Thrombectomy and Stenting as the First-Line Strategy in the Treatment of Phlegmasia Cerulea Dolens Caused by Iliac Vein Lesions.

BACKGROUND: Phlegmasia cerulea dolens (PCD) is a rare and serious complication of deep venous thrombosis and iliac vein lesions (IVLs) are the most common cause of PCD. The purpose of this study was to explore the safety and efficacy of single-stage endovascular thrombus removal and stenting to treat PCD caused by IVLs. METHODS: Clinical data of 13 patients with PCD secondary to IVL were retrospectively analyzed. They underwent endovascular thrombus removal, including rheolytic thrombectomy, manual aspiration thrombectomy, and simultaneous iliac vein stenting after thrombus removal. The safety and efficacy of single-stage endovascular thrombectomy and stenting in the treatment of PCD were evaluated. RESULTS: The technical success rate was 100% (13/13). Postoperative symptoms were significantly relieved in all patients. There were no perioperative major bleeding complications or other critical adverse events. Two (15.4%) patients had slightly elevated serum creatinine concentration after surgery, which returned to normal before discharge. At the 12-month follow-up, the stent primary patency rate was 81.8% and there were no cases of severe post-thrombotic syndrome. CONCLUSIONS: Single-stage endovascular thrombectomy and stenting in PCD due to IVLs was minimally invasive, safe, and effective; it is recommended as a first-line treatment for PCD caused by IVLs.

Augmentation of miR-202 in varicose veins modulates phenotypic transition of vascular smooth muscle cells by targeting proliferator-activated receptor-γ coactivator-1α.

In varicose veins, vascular smooth muscle cells (VSMCs) often show abnormal proliferative and migratory rates and phenotypic transition. This study aimed to investigate whether microRNA (miR)-202 and its potential target, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), were involved in VSMC phenotypic transition. miR-202 expression was analyzed in varicose veins and in VSMCs conditioned with platelet-derived growth factor. The effect of miR-202 on cell proliferation and migration was assessed. Furthermore, contractile marker SM-22α, synthetic markers vimentin and collagen I, and PGC-1α were analyzed by Western blot analysis. The modulation of PGC-1α expression by miR-202 was also evaluated. In varicose veins and proliferative VSMCs, miR-202 expression was upregulated, with decreased SM-22α expression and increased vimentin and collagen I expression. Transfection with a miR-202 mimic induced VSMC proliferation and migration, whereas a miR-202 inhibitor reduced cell proliferation and migration. miR-202 mimic constrained luciferase activity in HEK293 cells that were cotransfected with the PGC-1α 3'-untranslated region (3'-UTR) but not those with mutated 3'-UTR. miR-202 suppressed PGC-1α protein expression, with no influence on its messenger RNA expression. PGC-1α mediated VSMC phenotypic transition and was correlated with reactive oxygen species production. In conclusion, miR-202 affects VSMC phenotypic transition by targeting PGC-1α expression, providing a novel target for varicose vein therapy.

ox-LDL induces endothelial dysfunction by promoting Arp2/3 complex expression.

Oxidized low-density lipoproteins (ox-LDL) play a critical role in endothelial injury including cytoskeleton reorganization, which is closely related to actin-related protein 2/3 (Arp2/3) complex. The aim of this study was to investigate the role of Arp2/3 complex in ox-LDL-induced endothelial dysfunction. In this study, we found that Arp2 and Arp3 expression was increased under atherosclerotic conditions both in ApoE-/- mice and in ox-LDL-stimulated human coronary artery endothelial cells (HCAECs). Arp2/3 complex inhibitor CK666 significantly reduced ox-LDL-induced ROS generation and cytoskeleton reorganization, and increased NO release in HCAECs. Pretreatment with LOX-1- but not CD36-blocking antibody markedly decreased ox-LDL-induced Arp2 and Arp3 expression. Moreover, Rac-1 siRNA remarkably suppressed ox-LDL-stimulated Arp2 and Arp3 expression. Additionally, CK666 reduced endothelial nitric oxide synthase (eNOS) expression and atherosclerotic lesions in ApoE-/- mice. Collectively, ox-LDL induces endothelial dysfunction by activating LOX-1/Rac-1 signaling and upregulating Arp2/3 complex expression.

Comparison of uncovered stent placement across versus above the main duodenal papilla for malignant biliary obstruction.

PURPOSE: To evaluate the differences in efficiency and complications of metal stent insertion across versus above the main duodenal papilla (MDP) in patients with malignant obstruction of the common bile duct (CBD). MATERIALS AND METHODS: Records of 98 consecutive patients who underwent stent insertion for malignant CBD obstruction between 2004 and 2010 were retrospectively reviewed. Fifty-one patients (group 1) and 47 patients (group 2) were treated with stent insertion across and above the MDP, respectively. Primary stent patency, overall survival, complications, and changes in serum bilirubin level following stent insertion were assessed. RESULTS: Infection appeared in 12 and four patients, respectively, in groups 1 and 2. The respective mean primary stent patency times were 307.8 days ± 20.2 and 490.7 days ± 40.7, and mean survival times were 245.1 days ± 17.4 and 286.3 days ± 20.2. Bilirubin reduction rates were 55.7% ± 16.6 and 61.1% ± 13.7 at 1 week and 84.2% ± 5.7 and 86.2% ± 5.7 at 1 month in groups 1 and 2, respectively. In group 2, the rate of infection was significantly lower (P = .044) and primary stent patency was longer (P = .019). However, there was no significant difference between groups in survival time (P = .074) or bilirubin reduction rate at 1 week (P = .083) or 1 month (P = .082). CONCLUSIONS: Bile stent insertion above the MDP may achieve longer stent patency and a lower infection rate compared with placement across the MDP. For patients with malignant CBD obstruction, biliary stents should be placed above the papilla if papillary lesions are not invaded.

In silico intravascular optical coherence tomography (IVOCT) for quality assured imaging with reduced intervention.

In the clinical application of intravascular optical coherence tomography (IVOCT), it is necessary to flush opaque blood during image acquisition. However, there are no specific standards for how to perform low-dose but effective flushing. In this study, computational fluid dynamics (CFD) and optical models were integrated to numerically simulate the complete process of IVOCT, which includes blood flushing with normal saline followed by image acquisition. Moreover, an intermittent injection scheme was proposed, and its advantages over the conventionally adopted scheme of continuous injection were verified. The results show that intermittent injection can significantly reduce the dosage of normal saline (reduced by 44.4%) with only a slight sacrifice of image quality (reduced by 8.7%, but still acceptable). The developed model and key findings in this work can help surgeons practice optimized IVOCT operations and potentially lead to improved designs of the IVOCT equipment.

Numerical modelling of the interaction between dialysis catheter, vascular vessel and blood considering elastic structural deformation.

The dialysis catheter indwelling in human bodies has a high risk of inducing thrombus and stenosis. Biomechanical research showed that such physiological complications are triggered by the wall shear stress of the vascular vessel. This study aimed to assess the impact of CVC implantation on central venous haemodynamics and the potential alterations in the haemodynamic environment related to thrombus development. The SVC structure was built from the images from computed tomography. The blood flow was calculated using the Carreau model, and the fluid domain was determined by CFD. The vascular wall and the CVC were computed using FEA. The elastic interaction between the vessel wall and the flow field was considered using FSI simulation. With consideration of the effect of coupling, it was shown that the catheter vibrated in the vascular systems due to the periodic variation of blood pressure, with an amplitude of up to 10% of the vessel width. Spiral flow was observed along the catheter after CVC indwelling, and recirculation flow appeared near the catheter tip. High OSI and WSS regions occurred at the catheter tip and the vascular junction. The arterial lumen tip had a larger effect on the WSS and OSI values on the vascular wall. Considering FSI simulation, the movement of the catheter inside the blood flow was simulated in the deformable vessel. After CVC indwelling, spiral flow and recirculation flow were observed near the regions with high WSS and OSI values.

The safety and feasibility of using a 5-Fr guiding catheter with a 0.035-inch guidewire in place for cerebral angiography.

BACKGROUND: This study aimed to evaluate the safety and efficacy of performing diagnostic cerebral angiography using a 5-Fr guiding catheter with a 0.035-inch guidewire in place. METHODS: Actual flow rates at different pressures using the 5-Fr guiding catheter with a 0.035-inch guidewire in place were measured in vitro. Integrity of the guidewire surface after high-pressure injection was determined by examination under a light microscope and scanning electron microscope. Injected and unused contrast medium were collected and analyzed using a particle detector. Furthermore, a prospective randomized controlled study was conducted to compare safety and efficacy between the guided (guidewire in place) and conventional methods. RESULTS: The maximum injection pressure at a flow rate of 5 mL/s for the various types of commonly used contrast medium was approximately 350 psi, which is below the pressure limit for cerebral angiography. The guidewire surface remained relatively intact after multiple high-pressure injections. Procedure success and primary success rates did not significantly differ between the guided and conventional methods. However, procedure time (25.93 ± 4.07 vs 31.55 ± 5.49 minutes) and radiation exposure time (12.16 ± 3.82 vs 17.27 ± 6.12 minutes) were significantly shorter in the guided method group. CONCLUSION: The guided catheterization method is safe and feasible for cerebral angiography and has several advantages over the conventional method.

Analysis of the association between an insertion/deletion polymorphism within the 3' untranslated region of COL1A2 and chronic venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) is a common cause of leg pain and swelling and is commonly associated with varicose veins. It has significant socioeconomic consequences and is among the most common problems encountered in surgical practice. Although our current understanding of the pathogenesis of CVI is far from clear, there is a growing body of evidence suggesting a genetic contribution to the etiology of CVI. METHODS: By analyzing 254 CVI cases and 508 healthy controls in a Chinese population, we used a candidate gene approach to evaluate the association between a 7-base pair insertion/deletion (indel) polymorphism (rs3917) in the 3' untranslated region (3'UTR) of the alpha-2 type I collagen gene (COL1A2) and CVI susceptibility. Logistic regression was used to analyze the association between rs3917 and CVI risk, adjusted for sex and age. Computational modeling was used to predict potential molecular mechanisms underlying the association. RESULTS: Logistic regression analysis revealed that subjects carrying indel or deletion/deletion genotypes had a significantly increased risk for CVI than individuals carrying insertion/insertion genotypes (adjusted odds ratio, 1.64; 95% confidence interval [CI], 1.10-2.45; P = 0.010). Carrying the 7-base pair deletion allele was associated with a 1.60-fold risk for CVI (95% CI, 1.11-2.31; P = 0.008). Computational modeling suggests that the rs3917 insertion allele lies within a predicted binding site (seed region) for microRNA-382 and that the deletion allele alters the affinity of microRNA-mRNA binding by disrupting the local structure of COL1A2 mRNA, presumably allowing for upregulated COL1A2 expression. CONCLUSIONS: Taken together, our data suggest that common genetic variations in COL1A2 may influence CVI risk, possibly through microRNA-382-mediated regulation. Replication of our studies in other populations will strengthen our understanding of this association.

Natural Course and Treatment of Symptomatic Spontaneous Isolated Superior Mesenteric Artery Dissection with Total True Lumen Occlusion.

OBJECTIVE: We retrospectively investigated the association between the imaging features of spontaneous isolated superior mesenteric artery dissection (SISMAD) accompanied by total true lumen occlusion and the clinical symptoms to identify the patients at high risk and establish personalized therapeutic options. METHODS: Among 261 patients with SISMAD, we selected 37 with Yun's type III dissection; 35 patients underwent successful conservative management and 2 patients underwent exploratory laparotomy. After discharge, all patients were periodically followed up on an outpatient basis. We recorded patients' general condition, symptoms, time until symptom relief, imaging findings and follow-up results. RESULTS: All patients experienced acute abdominal pain prior to admission, with an onset time of 29.95 ± 24.66 hours. The mean time until relief of abdominal pain in patients who received conservative treatment was 42.17 ± 38.09 hours. Correlation analysis revealed no correlation between the length of dissection or of the occluded segment and abdominal pain intensity. Pain scores were lower and time until pain relief was shorter in patients with a definite arc of Riolan (AOR) on admission than in those without an AOR. No collateral circulation was observed in the two patients who underwent exploratory laparotomy, and distal intestinal perfusion was poor in these cases. Complete and partial remodeling of the superior mesenteric artery (SMA) was observed in 6 and 16 patients, respectively at the 12-month follow-up. Although the SMA remained occluded in 12 patients, abundant collateral circulation was detected. Three patients were lost to follow-up. CONCLUSION: This study highlights that conservative treatment should be attempted as first-line therapy in most patients with Yun's type III SISMAD. Complete AOR can contribute to remission of clinical symptoms during the acute stage. Poor distal blood flow of occluded vessels may serve as an important indicator for identification of patients at high risk of ischemic intestinal necrosis.

Dural sinus stenting for idiopathic intracranial hypertension: factors associated with hemodynamic failure and management with extended stenting.

BACKGROUND: Some patients undergoing dural sinus stenting for idiopathic intracranial hypertension (IIH) develop clinical and hemodynamic failure (recurrence of the pressure gradient) owing to stent-adjacent stenosis. OBJECTIVE: To characterize factors associated with hemodynamic failure, and to describe outcomes of patients after repeat stenting. MATERIALS AND METHODS: We reviewed the initial and follow-up clinical, venographic, and hemodynamic data in 39 patients with IIH treated over 17 years with stenting. Thirty-two had follow-up angiographic and hemodynamic data at 1-99 months (mean 27.6, median 19.5 months). Eight patients were treated with 12 repeat stenting procedures, including extended stenting into the superior sagittal sinus (SSS). RESULTS: All patients had an initial successful hemodynamic result with the pressure gradient reduced from 10-43 to 0-7 mm Hg. 10/32 patients (31.3%), all women, developed new stenoses in the transverse sinus or posterior SSS above the stent with a recurrent pressure gradient. 7/9 patients with pure extrinsic stenosis of the transverse-sigmoid junction pre-stenting developed new stenoses and hemodynamic failure. All patients with hemodynamic failure who were restented had early and mid-term documented hemodynamic success at 1.7-50 months. They were free from papilledema at 3.8-50 months after the last restenting, and 11.5-99.5 months after initial stent placement (mean 45.3, median 38.5 months). CONCLUSIONS: Pure extrinsic compression of the transverse-sigmoid junction and female gender were strongly associated with hemodynamic failure. Eight patients with hemodynamic failure who were restented had successful control of papilledema, including 4/4 who had extended stenting into the SSS.

Loss of Limb by Inadvertent Embolization of the Persistent Sciatic Artery.

Persistent sciatic artery (PSA) is a rare anatomic variant and is normally clinically silent. It can be found occasionally during uterine arteries embolization (UAE) and can lead to technical failure or complications. The authors present a patient with bilateral PSAs who was referred for emergency UAE because of uncontrollable postabortion hemorrhage. Inadvertent embolization of the right PSA led to unsalvageable ischemia and amputation of the right lower limb 12 days later.

IQGAP1 modulates the proliferation and migration of vascular smooth muscle cells in response to estrogen.

Vascular smooth muscle cell (VSMC) proliferation and migration has been proven to be a critical event in the development of varicosity. Variations in estrogen levels, a pathological event related to age and pregnancy, play a role in the pathogenesis of varicosity. Previous studies have reported a different response of VSMCs following estrogen stimulation. However, the exact mechanisms involved have not yet been elucidated. In the present study, we examined the responses of lesion and normal VSMCs treated with 10(-8) M 17ß-estradiol (E2) for 24 h. A differential effect of exposure to E2 was observed in these cells. IQ-domain GTPase-activating protein 1 (IQGAP1), a scaffold protein, was overexpressed in the lesion VSMCs and was shown to modulate VSMC proliferation and migration in response to E2. Furthermore, the increased expression of IQGAP1 was found to be intimately associated with a high activity of estrogen receptor α (ERα), which has been implicated in the regulation of VSMC physiological function. Additionally, we found that two critical kinases, Akt and extracellular signal-regulated kinase (ERK), mediated the activation of ERα and VSMC proliferation. According to our results, we thus concluded that high levels of IQGAP1 in VSMCs regulate the physiological reaction of the cells in response to estrogen exposure, and that kinases are involved in the process by mediating ERα activation. In view of the essential role of IQGAP1 in the physiological function of VSMCs, targeting this molecule may prove to be a promising strategy for the treatment of varicosity.

IQGAP1 promotes the phenotypic switch of vascular smooth muscle by myocardin pathway: a potential target for varicose vein.

Recently, the architectural remodeling of venous vessel wall ranks as the basis of varicose veins development based on the phenotypic state of vascular smooth muscle cells (VSMCs). In this study, we firstly demonstrated an obvious up-regulation of IQ-domain GTPase-activating protein 1 (IQGAP1) in patients with varicose veins. Importantly, following stimulation with PDGF-BB for 4 h, a common inducer of phenotypic switch in VSMCs, a dramatically time-dependent increase in IQGAP1 expression was observed in human venous smooth muscle cells (HUVSMCs), concomitant with the down-regulation of SMC markers [including α-smooth muscle actin (SMA), smooth muscle calponin (CNN), SM22α (SM22)], suggesting a critical function of IQGAP1 during the switch of synthetic VSMC phenotype. Further analysis ascertained that IQGAP1 overexpression significantly inhibited the expression of SMA, SM and CNN, while its silencing dramatically promoted their expression levels. Moreover, the elevated IQGAP1 enhanced cell proliferation, migration and rearrangement. Mechanism assay confirmed that IQGAP1 overexpression notably blocked myocardin levels. Importantly, after transfection with myocardin siRNA, IQGAP1 down-regulation-induced decrease in cell proliferation, migration and cell rearrangement was remarkably attenuated. Together, these results demonstrated that IQGAP1 may regulate the phenotypic switch of VSMCs by myocardin pathway, which is critical for the pathological progression of varicose vein. Therefore, this study supports a prominent insight into how IQGAP1 possesses its benefit function in varicose veins development by regulating vascular remodeling.

Placement of vena cava filter via percutaneous puncture of the great saphenous vein.

The aim of this study was to investigate the feasibility and safety of vena cava filter (VCF) placement via percutaneous puncture of the great saphenous vein (GSV) in the prevention of pulmonary embolisms. Using ultrasound positioning, VCF placement via percutaneous puncture of the GSV was performed on 12 patients with deep vein thrombosis (DVT) in the lower extremities. Transcatheter thrombolysis was conducted simultaneously. The postoperative filter position, puncture wound recovery and fluency of the GSV were observed. All filters were successfully released, with accurate positioning. No hematoma was observed at the puncture point during the perioperative period. In certain patients, local petechiae appeared around the puncture point during the thrombolysis period, which did not require special treatment. Re-examination using ultrasound revealed unobstructed blood flow in the GSV. VCF placement via percutaneous puncture of the GSV is a new filter placement method. The feasibility and safety of this method for the prevention of pulmonary embolisms has been demonstrated in a small number of sample cases.

The mitochondrial DNA 9-bp deletion polymorphism is a risk factor for hepatocellular carcinoma in the Chinese population.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Although molecular biology of carcinogenesis and tumor progression of HCC has been increasingly understood with intense research in recent years, the molecular and cellular mechanisms of HCC pathogenesis are still poorly understood. In the present study, a case-control study including 390 HCC patients and 431 healthy controls was conducted to investigate the association of HCC susceptibility with the mitochondrial DNA (mtDNA) 9-bp deletion polymorphism in Chinese population. Chi-square testing showed that frequencies of 9-bp one repeat or two repeats were significantly different between HCC and control groups. Carriage of 9-bp one repeat fragment was associated with a significantly increased risk of developing HCC (odds ratio=1.48, 95% confidence interval: 1.03-2.14, p=0.027). Stratification analysis further showed that the differences between cases and controls were more obvious in drinkers than nondrinkers. Computational modeling of the 9-bp deletion polymorphism suggests that the mtDNA sequence without the 9-bp deletion polymorphism lies within a predicted binding site (seed region) for hsa-miR-519c-5p and hsa-miR-526a. Our data suggested that the 9-bp deletion polymorphism in mitochondria may influence HCC risk, likely through specific microRNA-mediated regulation, which was possibly involved in the pathogenesis of HCC. The replication of our studies in other populations with larger sample size is warranted.