ARF6 plays a general role in targeting palmitoylated proteins from the Golgi to the plasma membrane.

Protein palmitoylation is a post-translational lipid modification of proteins. Accumulating evidence reveals that palmitoylation functions as a sorting signal to direct proteins to destinations; however, the sorting mechanism remains largely unknown. Here, we show that ARF6 plays a general role in targeting palmitoylated proteins from the Golgi to the plasma membrane (PM). Through shRNA screening, we identified ARF6 as the key small GTPase in targeting CD36, a palmitoylated protein, from the Golgi to the PM. We found that the N-terminal myristoylation of ARF6 is required for its binding with palmitoylated CD36, and the GTP-bound form of ARF6 facilitates the delivery of CD36 to the PM. Analysis of stable isotope labeling by amino acids in cell culture revealed that ARF6 might facilitate the sorting of 359 of the 531 palmitoylated PM proteins, indicating a general role of ARF6. Our study has thus identified a sorting mechanism for targeting palmitoylated proteins from the Golgi to the PM.

Mid-term Results of the Treatment of Isolated Dissection of the Celiac Artery: A Comparative Analysis of Endovascular Versus Conservative Therapy.

OBJECTIVES: Endovascular treatment (EVT) is an alternative method used to treat isolated dissection of the celiac artery (IDCA). However, only a few mid-term results have been reported. This study aimed to analyze and compare the outcomes of endovascular and non-operative therapies for IDCA. METHODS: Data from a cohort of consecutive IDCA patients enrolled in the study hospital between April 2012 and September 2020 were retrospectively reviewed. Demographic information, imaging features, treatment modalities, and follow-up results of celiac artery remodeling and adverse events were collected and analyzed. RESULTS: A total of 87 patients were enrolled in the study. Stents were deployed in 68 patients, and non-operative treatment (blood pressure control and pain management) was continued in the remaining 19 patients who did not receive stenting; among these 19 patients, EVT failed in 6. The mean follow-up period was 37.3 (range, 10-85 months) and 44.0 (range, 9-80 months) months in the EVT and non-operative groups, respectively. During follow-up, the overall complete remodeling (absence of residual dissection with no false lumen or no intramural thrombus) rate was significantly higher in the EVT group than in the non-operative group (87.3% vs 7.1%, p<0.001). The incomplete remodeling (improved true lumen with malabsorption or partial thrombosis of the false lumen) rate was not significantly different between the EVT and non-operative groups (6.3% vs 14.3%; p=0.2984). Meanwhile, the adverse event-free survival rates were 89.0%, 67.0%, and 67.0% at 1, 3, and 5 years, respectively, in the EVT group compared with 39.7% and 29.8% at 1 and 3 years in the non-operative group (p<0.0001). CONCLUSIONS: EVT for IDCA may be considered an effective management option with a favorable clinical success rate, an encouraging complete remodeling rate, and a satisfactory adverse event-free survival rate. However, further evaluation with a long-term follow-up is required. CLINICAL IMPACT: Endovascular intervention for isolated dissection of the celiac artery has attracted inadequate attention. In this retrospective study with comparative analysis of endovascular versus conservative therapy for isolated dissection of the celiac artery patients, a better complete remodeling rate and a higher adverse event-free survival rate were observed in the endovascular treatment (EVT) group during follow-up, indicating that EVT could be an effective management option for isolated dissection of the celiac artery.

LncRNA SNHG15 relieves hyperglycemia-induced endothelial dysfunction via increased ubiquitination of thioredoxin-interacting protein.

Numerous studies have revealed that hyperglycemia is a pivotal driver of diabetic vascular complications. However, the mechanisms of hyperglycemia-induced endothelial dysfunction in diabetes remain incompletely understood. This study aims to expound on the underlying mechanism of the endothelial dysfunction induced by hyperglycemia from the perspective of long non-coding RNAs (lncRNA). In this study, a downregulation of SNHG15 was observed in the ischemic hind limb of diabetic mice and high glucose (HG)-treated HUVECs. Functionally, the overexpression of SNHG15 promoted cell proliferation, migration, and tube formation, and suppressed cell apoptosis in HG-treated HUVECs. Mechanistically, SNHG15 reduced thioredoxin-interacting protein (TXNIP) expression by enhancing ITCH-mediated ubiquitination of TXNIP. TXNIP overexpression abrogated the protective effect of lncRNA SNHG15 overexpression on HG-induced endothelial dysfunction. The following experiment further confirmed that SNHG15 overexpression promoted angiogenesis of the ischemic hind limb in diabetic mice. In conclusion, SNHG15 is a novel protector for hyperglycemia-induced endothelial dysfunction via decreasing TXNIP expression.

Experimental Analysis of the Quality of Needle-Assisted Fenestration in Aortic Stent-Grafts and the Differences Between Gradual and Rapid Balloon Dilation.

Purpose: To report the findings of an in vitro experiment to evaluate the quality of needle fenestrations dilated by different size balloons in various stent-grafts and to investigate the differences between gradual and rapid dilation. Materials and Methods: Fenestrations were made using an 18-G needle in 5 different polyester or expanded polytetrafluoroethylene (ePTFE) stent-grafts: Relay, Valiant, Hercules, TAG, and Ankura. Each stent-graft received 2 groups of fenestrations: one was followed by gradual sequential dilation (4-, 6-, 8-, and 10-mm balloons) and the other by rapid dilation (4- and 10-mm balloons). The pressure was increased to 10 atmospheres or until the balloon was fully inflated with no waist. Quantitative and qualitative evaluations, including fenestration diameter, area, shape, and margins were conducted using light microscopy and scanning electron microscopy. Results: Relay had the strongest resistance to dilation and Ankura the slightest. The maximum length and area of holes expanded as the balloon diameter increased. The fenestrations in polyester devices were mostly elliptical or slit-like, with limited tears but extensive fibers visible in the margin, while ePTFE stent-grafts showed larger fenestration areas with clearer margins. Ankura showed the best quality of fenestrations, which were always circular or square without fabric tears, while the holes in the TAG were square or elliptical but sometimes had a slit after large balloon dilation (≥6 mm). The Relay, Valiant, Hercules, and Ankura devices showed no difference in maximum diameter, fenestration area, or scores of shape and margin (p>0.05). Rapid dilation in the TAG increased the rate of uncontrolled fabric tear, resulting in a larger final diameter (12.90 vs 10.82 mm, p=0.047), smaller area (30.46 vs 41.09 mm2, p=0.028), worse shape (0.75 vs 1.20, p=0.268), and worse margin (0.40 vs 1.00, p=0.174). Though the decreased fenestration shape and margin scores did not reach statistical significance, the trend for decline was more obvious than with the other devices. Conclusion: Materials and structures of the stent-grafts determine the quality of fenestrations dilated by different size balloons. The use of sequential vs rapid balloon dilation is also crucial for fashioning high-quality fenestrations and should be selected judiciously.

Long-term Results of Thoracic Endovascular Aortic Repair for Type B Aortic Dissection and Risk Factors for Survival.

Purpose: To compare characteristics of acute, subacute, and chronic type B aortic dissection and their influence on long-term results of thoracic endovascular aortic repair (TEVAR). Materials and Methods: In a single-center, retrospective cohort study, 314 patients (median age 52 years; 244 men) with acute (n=165), subacute (n=115), or chronic (n=34) type B aortic dissection underwent TEVAR between January 2009 and December 2013. Patient demographics, risk factors, and imaging characteristics were compared among the groups. Univariable and multivariable Cox regression analyses were performed to identify any factors influencing survival. Results: The acute and subacute patients exhibited more complications at presentation than chronic patients. However, the chronic patients exhibited more aneurysmal dilatation (p<0.001) and true lumen collapse (p<0.001). Over a mean follow-up of 68.1±22.9 months (range 2-108), subacute patients showed a lower reintervention rate (3.6% vs 12.1% vs 12.1%, p=0.045), a lower major complication rate (14.4% vs 33.1% vs 27.3%, p=0.002), and better cumulative overall survival (p=0.03) than the acute and chronic groups, respectively. Furthermore, acute patients developed more stent-graft-induced distal erosion (p=0.017) and retrograde type A dissection (RTAD) (p=0.036), whereas chronic patients had less aortic remodeling in the stented segment (p<0.001), distal thoracic aorta (p<0.001), and abdominal aorta (p=0.047). Finally, multivariable analysis demonstrated age >52 years, visceral malperfusion, and RTAD as independent factors influencing overall survival; aneurysmal dilatation, rupture/impending rupture, and RTAD were independent factors influencing aorta-specific survival. Conclusion: Acute and subacute patients had increased risks of rupture and complications at presentation, whereas chronic patients had increased risks for aneurysmal dilatation. From a long-term perspective, the subacute phase might be an optimal time for TEVAR in cases of type B aortic dissection that do not need emergent interventions. The risk factors influencing survival should be identified, carefully managed, and possibly prevented.

A transcranial sonography study of brainstem and its association with depression in idiopathic generalized epilepsy with tonic-clonic seizures.

Brainstem raphe (BR) hypoechogenicity in transcranial sonography (TCS) has been depicted in patients with depression. But, up to date, the association of BR alterations in TCS with depression in patients with epilepsy has never been reported. This study was to investigate the possible role of BR examination via TCS in patients with idiopathic generalized epilepsy with tonic-clonic seizures (IGE-TCS) and depression. Forty-six patients with IGE-TCS and 45 healthy controls were recruited. Echogenicity of the caudate nuclei (CN), lentiform nuclei (LN), substantia nigra (SN), and BR and widths of the lateral ventricle (LV) frontal horns and the third ventricle (TV) were assessed via TCS. The determination of depression was based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV), and depression severity measured by Chinese version Neurological Disorders Depression Inventory for Epilepsy (C-NDDI-E) and Beck Depression Inventory-II (BDI-II). The width of TV in patients with epilepsy was found significantly larger than that in healthy controls (p = 0.001), but there was no significant difference in TV width between patients with IGE-TCS with and without depression. There were no significant differences between patients with IGE-TCS and healthy controls in LV frontal horn width, as well as in SN, CN, LN, and BR echogenicity. Here, it seems that patients with IGE-TCS were detected with smaller SN echogenic area compared with controls though they had no statistical significance. Patients with IGE-TCS with hypoechogenic BR had significantly higher C-NDDI-E and BDI-II scores than those with normal BR signal, and most patients with IGE-TCS with depression exhibited hypoechogenic BR, but few patients with IGE-TCS without depression exhibited hypoechogenic BR. In conclusion, BR echogenic signal alterations in TCS can be a biomarker for depression in epilepsy, but it might not be associated with epilepsy itself. The alterations of SN echogenic area and TV width in TCS may reflect a potential role of SN and diencephalon structure in the pathogenesis of epilepsy, which needs to be further elucidated.

Favourable Outcomes of Endovascular Total Aortic Arch Repair Via Needle Based In Situ Fenestration at a Mean Follow-Up of 5.4 Months.

OBJECTIVES: Endovascular repair of aortic arch pathologies remains challenging. Recently, needle based in situ fenestration (ISF) has shown great potential in endovascular total aortic arch repair (ETAAR). This study aimed to evaluate the feasibility, effectiveness, and safety of ETAAR via needle based ISF, and to present initial experience with this technique. DESIGN AND METHODS: Patients who met the inclusion criteria were enrolled in this prospective study. The supra-arch branches were manually punctured in a retrograde manner using liver biopsy needles (18 gauge/30 cm) in the left common carotid artery (LCCA) and brachiocephalic trunk (BCT), and endo-puncture system or aspiration biopsy needles (21-gauge) in the left subclavian artery (LSA). All the branches were revascularised with bridge stents. Routine follow-up occurred at 1, 3, 6, and 12 months post surgery. RESULTS: Ten patients with arch pathologies underwent ETAAR. Revascularisation of three branches was successfully performed in eight patients, but attempts to create ISF in LSA were unsuccessful in two patients because of tortuosity and sharp angle. The time taken to establish ISF in LCCA and BCT was 100.4s and 489.6s, respectively. Bilateral regional cerebral oxygen saturation (RCOS) decreased after the arch endograft deployment (both, p < .001) and recovered to the pre-operative level once both carotid arteries were reconstructed (left, p = .0856; right, p = .6). The right RCOS was higher with the beneficial effect of extracorporeal circulation (after cTAGs deployment, p < .001; after LCCA revascularised, p = .0148) during the ischaemic period. In one case, the left iliac artery ruptured, but no ISF related or neurological complications occurred. An early follow-up (mean 5.44 months) CTA and ultrasound confirmed patency of all the branch grafts without any endoleak or migration CONCLUSIONS: This study demonstrated that ETAAR via needle based ISF, making full use of off the shelf devices and techniques, can be successfully performed in aortic arch pathologies with a favourable early outcome.

Advanced Glycation End-Products Downregulate HoxA9EC through Activation of Nuclear Factor Kappa B by Reciprocal Interaction.

Advanced glycation end-products (AGEs) have been recognized as an important pathophysiological mechanism in endothelial dysfunction during diabetic atherogenesis. Homeobox (Hox) genes have been identified as playing a regulatory role in the adult cardiovascular system. Regulation of HoxA9EC is involved in diabetic endothelial dysfunction, but the mechanism of HoxA9EC regulation has remained undefined. Here, we sought to investigate how HoxA9EC is regulated in AGE-induced endothelial dysfunction and to explore the mechanism involved. We used human umbilical venous endothelial cells (HUVECs) cocultured with AGEs, and examined endothelial nitric oxide synthase (eNOS) activation, nitric oxide (NO) release, cell migration, and the expression of HoxA9EC and nuclear factor kappa B (NF-κB). AGEs suppressed eNOS activation, NO release, and the migration of HUVECs. Knockout of HoxA9EC also reduced eNOS activation, NO release, and the migration of HUVECs, and the enhancement of HoxA9EC improved the function of HUVECs. Furthermore, AGEs downregulated HoxA9EC expression and activated NF-κB, and the depression of HoxA9EC was significantly attenuated by the NF-κB inhibitor. On the other hand, knockout of HoxA9EC activated NF-κB and the enhancement of HoxA9EC suppressed NF-κB activation. In conclusion, AGEs could induce endothelial dysfunction through NF-κB-dependent HoxA9EC downregulation by reciprocal interaction, and the enhancement of HoxA9EC expression could attenuate the impairment.

Morphologic findings and management strategy of spontaneous isolated dissection of the celiac artery.

OBJECTIVE: We report the morphologic findings and treatment of spontaneous isolated dissection of the celiac artery (SIDCA). METHODS: Twenty-three patients with SIDCA presenting between January 2009 and December 2014 were enrolled in this retrospective study. The demographic data, clinical features, morphologic findings, treatment modalities, and follow-up results of these patients were reviewed. We proposed a morphologic classification for SIDCA similar to that of spontaneous isolated dissection of the superior mesenteric artery. RESULTS: Initially, 11 patients were treated endovascularly, and 12 were treated medically. Four patients treated medically had an aggravation of the dissection and needed endovascular salvage. All patients recovered successfully. None of the patients developed abdominal pain, required reintervention, or died. In the medically treated group, the false lumen was completely thrombosed and absorbed in 4 patients, partially thrombosed in 2, and patent in 2. All stents were patent with the false lumen completely thrombosed and absorbed in the endovascular group. CONCLUSIONS: SIDCA can be treated medically in stable patients but requires intensive follow-up. Endovascular therapy can be applied in high-risk patients with recurrent symptoms, visceral malperfusion, or aneurysm. Open surgery should be considered if endovascular repair is not suitable or has failed. The short-term results of endovascular management are encouraging but further evaluation with long-term follow-up is necessary.