ALAS2 overexpression alleviates oxidative stress-induced ferroptosis in aortic aneurysms via GATA1 activation.

Background: Aortic aneurysm, characterized by abnormal dilation of the aorta, poses significant health risks. This study aims to investigate the interaction between 5-aminolevulinate synthase 2 (ALAS2) and GATA-binding protein 1 (GATA1) in ferroptosis and oxidative stress responses in aortic aneurysm. Methods: A weighted gene co-expression network analysis (WGCNA) was performed on the differentially expressed genes (DEGs) within the GSE9106 dataset to identify the key module. Subsequently, protein-protein interaction (PPI) network analysis was performed on the key module. Mouse aortic vascular smooth muscle cells (MOVAS) were treated with hydrogen peroxide (H2O2) to induce oxidative stress, and ferroptosis inducers and inhibitors were added to evaluate their effects on iron content and oxidative stress markers. Through a series of in vitro cellular experiments, we assessed cell viability, expression levels of GATA1 and iron mutation-associated proteins, as well as cellular phenotypes such as inflammatory responses and apoptosis rates. Results: Three candidate genes (ALAS2, GYPA, and GYPB) were upregulated in the thoracic aortic aneurysm (TAA) samples of the GSE9106 dataset. The H2O2 treatment increased the MOVAS cells' iron content and oxidative stress, upregulated ALAS2 protein levels, and decreased the ferroptosis-related protein levels. ALAS2 overexpression reversed H2O2-induced apoptosis and increased the inflammatory cytokine levels. Additionally, the knockdown of GATA1 partially reversed the protective mechanism of overexpressed ALAS2 on H2O2-induced ferroptosis. Conclusions: ALAS2 overexpression reduced H2O2-induced oxidative damage and iron-induced apoptosis in MOVAS cells, and GATA1 knockdown partially reversed this protective effect. These findings suggested that the ALAS2 and GATA1 regulatory pathways may be potential therapeutic targets in aortic aneurysms.

Endovascular Treatment of Superior Mesenteric Artery Pseudoaneurysm Due to Infective Endocarditis With Stent-Graft.

PURPOSE: To report a successful case of pseudoaneurysm of the superior mesenteric artery (SMA) caused by infected endocarditis treated with a covered stent. CASE REPORT: A patient was diagnosed with infective endocarditis and 2 months later a proximal SMA pseudoaneurysm was identified on computed tomography. Daptomycin was started on admission and continued for approximately 4 months until the inflammatory markers normalized, and then the SMA pseudoaneurysm was successfully excluded with a stent-graft and antibiotics were continued for 1 year after the procedure. There were no associated complications or recurrences at the 3-year follow-up. CONCLUSION: Placing a covered stent with a full course of antibiotics before and after surgery may be a successful alternative to open surgery in the treatment of pseudoaneurysms of the SMA due to infective endocarditis. CLINICAL IMPACT: This case report reports a rare case of pseudoaneurysm of the superior mesenteric artery due to infective endocarditis, which was successfully treated with an overlapping stent and confirmed by complete imaging data at a three-year follow-up. This report suggests that endovascular treatment may be an alternative to open surgery in the treatment of pseudoaneurysms of the superior mesenteric artery caused by infective endocarditis.

Acute Renal Infarction Due to Symptomatic Isolated Spontaneous Renal Artery Dissection: A Rare and Fatal Disease.

OBJECTIVE: To report demographics and clinical, laboratory, and imaging features of acute renal infarction (ARI) due to symptomatic isolated spontaneous renal artery dissection (SISRAD) and to analyze outcomes after the initial therapy for SISRAD. METHODS: Thirteen patients with ARI due to SISRAD between January 2016 and March 2021 were enrolled in this retrospective study. We reviewed the demographics, clinical, laboratory, and imaging features (location of the infarct kidney, the branch artery involved by dissection, true lumen stenosis, false lumen thrombosis, and aneurysm), treatment modalities, and follow-up results; analyzed the difference between SISRAD and other causes of ARI; and propose an appropriate therapy strategy for SISRAD based on our data and literature. RESULT: Patients with ARI due to SISRAD were mostly young men (43 [24-53] years; 12/13 [92%]). No patients had atrial fibrillation or acute kidney injury at admission (0/13). All 13 patients received conservative treatment as the initial treatment. Sixty-two percent (8/13) of patients progressed, and 88% (7/8) of them had dissection aneurysm on the admission computed tomographic angiography (CTA) image. Seventy-five percent (6/8) of patients underwent endovascular intervention as follows, stent placement in 1 patient, renal artery embolization in 1, and stent placement with embolization in 4. Two patients with disease progression died: 1 during the conservative treatment period and 1 after the stent placement. Thirty-eight percent (5/13) of patients in remission continued to receive conservative treatment, none of whom had dissection aneurysm on the admission CTA. CONCLUSION: Symptomatic isolated spontaneous renal artery dissection is a rare and fatal disease. For young ARI patients with no previous history of tumors and cardiogenic diseases, CTA examination is recommended to exclude SISRAD. Dissection aneurysm seems to be a risk of progression for SISRAD in this series. Conservative treatment, a recognized initial treatment, has a good effect on patients without dissection aneurysm, and we recommend endovascular intervention as the initial treatment for the patient with dissection aneurysm at admission. Multicenter clinical studies are needed to explore a more-appropriate treatment for patients with SISRAD. CLINICAL IMPACT: This article report the related factors, risks, demographics and laboratory data of Acute renal infarction (ARI) due to Symptomatic isolated spontaneous renal artery dissection (SISRAD) and explore a better initial therapy strategy for SISRAD. It will help improve the effectiveness of SISRAD treatment and reduce the mortality rate from this rare but lethal disease.

Mid-term Outcomes of Physician-Modified Fenestrated or Branched Endovascular Repair for Post-dissection Thoracoabdominal Aortic Aneurysms.

PURPOSE: To report the early experience and mid-term outcomes of physician-modified fenestrated or branched endovascular repair (PM-F/BEVAR) for patients with post-dissection thoracoabdominal aortic aneurysm (PD-TAAA). METHODS: PD-TAAA patients treated with PM-F/BEVAR between December 2014 and September 2020 in our institution were retrospectively analyzed. RESULTS: Out of the 39 patients, technical success defined as successful deployment of all stent grafts with patent target vessels (TVs) and exclusion of the lesion without type I or III endoleak was achieved in 35 patients (89.7%). A total of 126 TVs were successfully reconstructed. Thirty-day mortality was 0%. Seven major adverse events occurred including one acute kidney injury, four renal infarctions, one retroperitoneal hematoma and one left renal artery occlusion. Seven type II endoleak and three type III endoleak were detected. During a mean 29.4 ± 15.5 months follow-up period, the mortality was zero. Three renal arteries and one external iliac artery occluded in four patients. No other new onset major adverse event occurred. No patient required reintervention. One type II endoleak spontaneously resolved, while the remaining six remained stable. One early type III endoleak diminished, and one new type III endoleak occurred at 2 months. The primary patency of TV was 96.8% (120/124). Shrinkage or stability of aneurysm diameter can be observed in 38 patients (97.4%). The false lumen thrombosis rate was 89.7% (35/39). CONCLUSIONS: The present study showed encouraging results of PM-F/BEVAR for treatment of PD-TAAAs. LEVEL OF EVIDENCE: Level 4, Case Series.

Long-Term Aortic Remodeling After Thoracic Endovascular Aortic Repair of Acute, Subacute, and Chronic Type B Dissections.

Objective: This study aimed to investigate the characteristics and predictors of aortic remodeling over a long-term follow-up period after thoracic endovascular aortic repair (TEVAR) for acute, subacute, and chronic type B aortic dissections (TBADs). Methods: Patients who underwent TEVAR for TBAD from July 2011 to December 2013 were included, and relevant data were retrospectively analyzed. Results: After TEVAR, the true lumen (TL) dimension increased and the false lumen (FL) dimension decreased or did not change over a 5-year follow-up period in all three temporal groups. Shrinkage proportion of the thoracic aorta was the highest in the subacute group (acute, 28.1%; subacute, 39.1%; and chronic, 17.4%; p = 0.048), while abdominal expansion showed no significant differences among the groups (acute, 29.6%; subacute, 40.5%; and chronic, 44.4%; p = 0.502). The chronic group had a rate of complete FL regression, which is lower than the subacute or acute group at all anatomic sections, with significant differences only in the stented section (chronic, 21.7%; acute, 92.2%; and subacute, 80.4%; p < 0.05) and in the distal thoracic aortic section (chronic, 13.0%; acute, 31.1%; and subacute, 50.0%; p < 0.05). Logistic regression analysis demonstrated that chronic dissection, TL compression, endoleak, the number of branches from FL, and the number of residual tears affected optimal FL remodeling. Conclusion: The present study provides data on aortic remodeling of TBAD after TEVAR during a long-term follow-up period. The features and risk factors of aortic remodeling in the acute, subacute, and chronic phases are different in different aortic segments. These findings may have implications in the timing of TEVAR.

Hsa_circ_0008360 sponges miR-186-5p to target CCND2 to modulate high glucose-induced vascular endothelial dysfunction.

Vascular endothelial dysfunction is associated with the progress of many diseases. Circular RNAs (circRNAs) take part in the dysfunction of vascular endothelium. CircRNA hsa_circ_0008360 (circ_0008360) is dysregulated in high glucose-treated vascular endothelium, while the role and mechanism of circ_0008360 in high glucose-induced dysfunction remain unknown. Human umbilical vascular endothelium cells (HUVEC) were stimulated via high glucose. The abundances of circ_0008360, miR-186-5p and cyclin D2 (CCND2) were examined via quantitative real-time polymerase chain reaction or western blot. Vascular endothelial dysfunction was assessed via cell viability, apoptosis, migration and tube formation. The target relationship between miR-186-5p and circ_0008360 or CCND2 was analyzed via dual-luciferase reporter, RNA pull-down and RNA immunoprecipitation analyses. Circ_0008360 expression was enhanced in high-glucose-treated HUVEC. Circ_0008360 silence mitigated high glucose-induced suppression of viability, migration, tube formation, and increase in apoptosis in HUVEC. MiR-186-5p was sponged by circ_0008360, and miR-186-5p inhibition reversed the effect of circ_0008360 silence on high glucose-induced vascular endothelial dysfunction. MiR-186-5p alleviated high glucose-induced vascular endothelial dysfunction via targeting CCND2. CCND2 interference abolished the aggravated effect of circ_0008360 on high glucose-induced vascular endothelial dysfunction. Circ_0008360 knockdown attenuated high glucose-induced vascular endothelial dysfunction via regulating miR-186-5p and CCND2, indicating circ_0008360 might act as a target for the treatment of vascular endothelial dysfunction.Abbreviations: circRNAs, circular RNAs; HUVEC, human umbilical vascular endothelium cells; CCND2, cyclin D2; XPNPEP3, X-prolyl aminopeptidase 3; ceRNAs, competing endogenous RNAs; miRNAs, microRNAs; qRT-PCR, quantitative real-time polymerase chain reaction; RIP, RNA immunoprecipitation; HIF-1α, hypoxia inducible factor 1 alpha; TLR3, toll-like receptor 3; AKAP12, A-Kinase Anchoring Protein 12; ox-LDL, oxidized low-density lipoprotein; HG, high glucose; NG, normal glucose.

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.

A Large Vascular Leiomyoma Arising from the Superficial Femoral Artery: Case Report and Systematic Review.

OBJECTIVE: Vascular leiomyomas are rare begin tumor comprising mature vascular smooth muscles that originate in the tunica media of the blood vessels. Most of the tumors arise from the veins. Only a dozen cases of artery-arising vascular leiomyoma have been reported, most of which are presented as small nodules in the hand. METHODS: Here we report an interesting case of a large artery-arising vascular leiomyoma and perform a systematic review. RESULTS: A 55-year-old man complained a 6 × 3 cm firm, mobile, tender and pulseless mass in the medial region of his left thigh. The computed tomography showed a well-demarcated fusiform tumor encircling the superficial femoral artery and was enhanced significantly with contrast. The patency of the superficial femoral artery was intact. The magnetic resonance image exhibited slightly hypointense relative to skeletal muscle on T1-weighted images and a heterogeneous appearance on T2-weighted images. We performed the en bloc resection of the tumor and used a vascular graft to revascularize the artery through end-to-end anastomosis. After histopathological assessments, the tumor was diagnosed as an artery-arising vascular leiomyoma. We also performed a systematic review on artery-arising leiomyomas, discovering 21 cases. Most of the artery-arising vascular leiomyomas were small nodules (mean length: 2.4cm) and most of them were superficial solitary mass located in the hand (13 cases, 62%). Excision of the tumor was an effective treatment. The histological subtype of the artery-arising vascular leiomyoma in all cases was solid type. During the follow-up of each patient, there was no recurrence. CONCLUSIONS: Artery-arising vascular leiomyomas are extremely rare. Most of them are painless and locate in the hand. Their pathological subtype is solid type in all patients. Due to their begin nature, excision is a cure with little chance of recurrence.

Nuclear Factor Kappa-B/Homeobox A9-Mediated Modulation of Leucine-Rich Repeat Flightless-Interacting Protein 1 Is Involved in Advanced Glycation End Product-Induced Endothelial Dysfunction.

BACKGROUND: Pathogenesis of cardiovascular diseases begins with endothelial dysfunction. Our previous study has shown that advanced glycation end products (AGE) could inhibit the expression of homeobox A9 (Hoxa9), thereby inducing endothelial dysfunction. Leucine-rich repeat flightless-interacting protein 1 (LRRFIP1) has been found to participate in a variety of pathological processes, but reports of its role in endothelial dysfunction are rare. OBJECTIVES: This study aims to investigate whether LRRFIP1 is involved in AGE-induced endothelial dysfunction through Hoxa9-mediated transcriptional activation. METHODS: Chromatin immunoprecipitation was used to detect the transcriptional regulation of Hoxa9 on LRRFIP1 promoters. Human umbilical vein endothelial cells were treated with AGE or pyrrolidinedithiocarbamate (nuclear factor kappa-B [NF-κB] inhibitor). Moreover, changes in apoptosis, proliferation, migration, release of nitric oxide, and angiogenesis were detected. RESULTS: Hoxa9 promotes LRRFIP1 expression by binding to the -LRRFIP1 promoter. Meanwhile, overexpression of LRRFIP1 inhibited phosphorylation of P65 and elevated expression of Hoxa9. Overexpression of LRRFIP1 or/and Hoxa9 reversed the effects of AGE on HUVEC. AGE-induced inhibition on the expression of LRRFIP1 and Hoxa9 could be reversed by the NF-κB inhibitor. CONCLUSION: LRRFIP1 is involved in AGE-induced endothelial dysfunction via being regulated by the NF-κB/Hoxa9 axis.

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

OBJECTIVE: Numerous evidence indicates that hyperglycemia is a pivotal driver of the vascular complications of diabetes. 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). MATERIALS AND METHODS: Cell proliferation, migration, apoptosis, and tube formation were measured by cell counting kit-8 assay, transwell assay, flow cytometry, and tube formation assay, respectively. RNA pull-down and RNA-binding protein immunoprecipitation were used to detect the interaction between lncRNA SNHG15 and thioredoxin-interacting protein (TXNIP). Co-immunoprecipitation was used to detect the ubiquitination level of TXNIP and the interaction between TXNIP and E3 ubiquitin ligase ITCH. RESULTS: 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. Mechanically, SNHG15 reduced 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. 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 non-coding RNA GAPLINC promotes angiogenesis by regulating miR-211 under hypoxia in human umbilical vein endothelial cells.

In this study, we investigated the role of a long non-coding RNA GAPLINC in angiogenesis using human umbilical vein endothelial cells (HUVEC). We found that hypoxia and hypoxia-inducible factor 1α (HIF-1α) increased the expression of GAPLINC in HUVEC cells. Moreover, GAPLINC overexpression down-regulated miR-211 and up-regulated Bcl2 protein expression. Further rescue experiments confirmed that hypoxia directly increased GAPLINC expression. GAPLINC overexpression also increased cell migration and vessel formation which promoted angiogenesis, and these changes were attributed to the increased expression of vascular endothelial growth factor receptors (VEGFR) and delta-like canonical notch ligand 4 (DLL4) receptors. Finally, we demonstrated that GAPLINC promotes vessel formation and migration by regulating MAPK and NF-kB signalling pathways. Taken together, these findings comprehensively demonstrate that overexpression of GAPLINC increases HUVEC cells angiogenesis under hypoxia condition suggesting that GAPLINC can be a potential target for critical limb ischaemia (CLI) treatment.

A Single Center Experience of In Situ Needle Fenestration of Supra-aortic Branches During Thoracic Endovascular Aortic Repair.

BACKGROUND: To report the early results and technical details of in situ needle fenestration during thoracic endovascular aortic repair (TEVAR). MATERIALS AND METHODS: Thirty-seven patients with thoracic aortic disease who underwent TEVAR with in situ needle fenestration in our department between February 2016 and April 2017 were included in this study. Their demographic information, clinical manifestations, periprocedural outcomes, and follow-up results were analyzed. RESULTS: In total, 96.4% of attempted fenestrations were successful (53/55). Fenestration of the left subclavian artery (LSA) was performed in 26 patients, fenestration of either the LSA or brachiocephalic trunk (BCT) plus the left common carotid artery (LCCA) was performed in six patients, and fenestration of the three supra-aortic branches was performed in five patients. In the three-fenestration group with five patients, the procedure was under the protection of a cardiopulmonary bypass. External iliac artery rupture occurred in one case. Cerebrovascular events occurred in three cases, and myocardial infarction occurred in one. One case had a branch stent graft stuck in the brachial artery. During a median follow-up of 21 months, two patients developed retrograde type A dissection, and one was subsequently treated with a stent graft and BCT fenestration. One case presented with numbness in the fingertips of the left hand, and computed tomography angiography (CTA) indicated stenosis of the branch stent in the LSA. CTA examination revealed no endoleaks or expansion of the aortic aneurysms in any of the patients. CONCLUSIONS: In situ needle fenestration of endografts in the aortic arch is technically feasible, yielding acceptable short-term results in a selected patient cohort. Further studies are needed to determine mid- and long-term outcomes before more widespread adoption.

Guidewire Loop Dissection Technique for Filter Strut Endothelialization.

Complex inferior vena cava (IVC) filter retrieval was usually in need of advanced techniques. Filter strut endothelialization without tilt of the filter was still one of the challenges. Therefore, we would like to describe the guidewire loop dissection technique, which required no extra equipment, to solve problem. A 53-year-old male had IVC filter for 8 months. Venogram showed no tilt of the apex and endothelialization of struts. The hook was snared but the filter cannot be retrieved. A fine guidewire was then advanced and formed a loop between the strut and the caval wall. With traction applied, the guidewire peeled the struts off the caval wall, resulting in the dissection of strut endothelialization. In the end, the filter was retrieved without injuring IVC. This technique was a feasible option for such circumstance.

[Progress on in situ fenestration during thoracic endovascular aortic repair].

Endovascular aortic arch repair remains challenging due to the complicated anatomy and the involved vital branches. Off-label techniques emerged during the last decade, including endografts with parallel stents (known as Chimney, Periscope, Sandwich), surgeon-modified endografts, and various other reported techniques. In situ fenestration of standard endografts represents another off-label endovascular means to maintain perfusion to aortic side branches located in the excluded area. Its principle is based on fenestration of an endograft following its deployment inside the vascular system. As data are emerging regarding in situ fenestration, the aim of this article is to review recent progress of technical descriptions, in vitro and clinic results of in situ fenestration from the available literature.