ONE-seq: epitranscriptome and gene-specific profiling of NAD-capped RNA.

The hub metabolite, nicotinamide adenine dinucleotide (NAD), can be used as an initiating nucleotide in RNA synthesis to result in NAD-capped RNAs (NAD-RNA). Since NAD has been heightened as one of the most essential modulators in aging and various age-related diseases, its attachment to RNA might indicate a yet-to-be discovered mechanism that impacts adult life-course. However, the unknown identity of NAD-linked RNAs in adult and aging tissues has hindered functional studies. Here, we introduce ONE-seq method to identify the RNA transcripts that contain NAD cap. ONE-seq has been optimized to use only one-step chemo-enzymatic biotinylation, followed by streptavidin capture and the nudix phosphohydrolase NudC-catalyzed elution, to specifically recover NAD-capped RNAs for epitranscriptome and gene-specific analyses. Using ONE-seq, we discover more than a thousand of previously unknown NAD-RNAs in the mouse liver and reveal epitranscriptome-wide dynamics of NAD-RNAs with age. ONE-seq empowers the identification of NAD-capped RNAs that are responsive to distinct physiological states, facilitating functional investigation into this modification.

MiR-127-3p enhances macrophagic proliferation via disturbing fatty acid profiles and oxidative phosphorylation in atherosclerosis.

BACKGROUND: Atherosclerosis is a chronic pathology, leading to acute coronary heart disease or stroke. MiR-127 has been found significantly upregulated in advanced atherosclerosis. But its function in atherosclerosis remains unexplored. We explored the role of miR-127-3p in regulating atherosclerosis development and its downstream mechanisms. METHODS: The expression profile of miR-127 in carotid atherosclerotic plaques of 23 patients with severe carotid stenosis was detected by RT-qPCR and in situ hybridization. Primary bone marrow-derived macrophages (BMDM) stimulated with oxidized low-density lipoprotein were used as an in vitro model. CCK-8, EdU, RT-qPCR, and flow cytometry were used to detect the proliferative capacity and polarization of BMDM, which were infected by lentivirus-carrying plasmid to upregulate or downregulate miR-127-3p expression, respectively. RNA sequencing combined with bioinformatic analysis and targeted fatty acid metabolomics approach were used to detect the transcriptome and lipid metabolites. The association between miR-127-3p and its target was verified by dual-luciferase activity reporting and Western blotting. Oxygen consumption rate of BMDM were detected using seahorse analysis. High-cholesterol-diet-fed low density lipoprotein deficient (LDLR-/-) mice, with-or-without carotid tandem-stenosis surgery, were treated with miR-127-3p agomir or antagomir to examine its effect on plaque development and stability. RESULTS: miR-127-3p, not -5p, is elevated in human advanced carotid atheroma and its expression is positively associated with macrophage accummulation in plaques. In vitro, miR-127-3p-overexpressed macrophage exhibites increased proliferation capacity and facilitates M1 polariztion whereas the contrary trend is present in miR-127-3p-inhibited macrophage. Stearoyl-CoA desaturase-1 (SCD1) is one potential target of miR-127-3p. miR-127-3p mimics decreases the activity of 3' untranslated regions of SCD-1. Furthermore, miR-127-3p downregulates SCD1 expression, and reversing the expression of SCD1 attenuates the increased proliferation induced by miR-127-3p overexpression in macrophage. miR-127-3p overexpression could also lead to decreased content of unsaturated fatty acids (UFAs), increased content of acetyl CoA and increased level of oxidative phosphorylation. In vivo, miR-127-3p agomir significantly increases atherosclerosis progression, macrophage proliferation and decreases SCD1 expression and the content of UFAs in aortic plaques of LDLR-/- mice. Conversely, miR-127-3p antagomir attenuated atherosclerosis, macrophage proliferation in LDLR-/- mice, and enhanced carotid plaque stability in mice with vulnerable plaque induced. CONCLUSION: MiR-127-3p enhances proliferation in macrophages through downregulating SCD-1 expression and decreasing the content of unsaturated fatty acid, thereby promoting atherosclerosis development and decreasing plaque stability. miR-127-3p/SCD1/UFAs might provide potential therapeutic target for anti-inflammation and atherosclerosis.

METTL3-mediated m6A modification of NORAD inhibits the ferroptosis of vascular smooth muscle cells to attenuate the aortic dissection progression in an YTHDF2-dependent manner.

Ferroptosis of vascular smooth muscle cells (VSMCs) is related to the incidence of aortic dissection (AD). Long non-coding RNA (lncRNA) NORAD plays a crucial role in the progression of various diseases. The present study aimed to investigate the effects of NORAD on the ferroptosis of VSMCs and the molecular mechanisms. The expression of NORAD, HUR, and GPX4 was detected using quantitative real-time PCR (qPCR) or western blot. Ferroptosis was evaluated by detecting lactate dehydrogenase (LDH) activity, lipid reactive oxygen species (ROS), malonaldehyde (MDA) content, L-Glutathione (GSH) level, Fe2+ content, and ferroptosis-related protein levels. The molecular mechanism was assessed using RNA pull-down, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter assay. The histology of aortic tissues was assessed using H&E, elastic Verhoeff-Van Gieson (EVG), and Masson staining assays. The data indicated that NORAD was downregulated in patients with AD and AngII-treated VSMCs. Overexpression of NORAD promoted VSMC growth and inhibited the ferroptosis induced by AngII. Mechanistically, NORAD interacted with HUR, which promoted GPX4 mRNA stability and elevated GPX4 levels. Knockdown of GPX4 abrogated the effects of NORAD on cell growth and ferroptosis of AngII-treated VSMCs. Moreover, METTL3 promoted m6A methylation of NORAD in an YTHDF2-dependent manner. In addition, NORAD attenuated AAD symptoms, incidence, histopathology, inflammation, and ferroptosis in AAD mice. In conclusion, METTL3-mediated NORAD inhibited ferroptosis of VSMCs via the HUR/GPX4 axis and decelerated AAD progression, suggesting that NORAD may be an AD therapeutic target.

Deletion of BACH1 Attenuates Atherosclerosis by Reducing Endothelial Inflammation.

BACKGROUND: The transcription factor BACH1 (BTB and CNC homology 1) suppressed endothelial cells (ECs) proliferation and migration and impaired angiogenesis in the ischemic hindlimbs of adult mice. However, the role and underlying mechanisms of BACH1 in atherosclerosis remain unclear. METHODS: Mouse models of atherosclerosis in endothelial cell (EC)-specific-Bach1 knockout mice were used to study the role of BACH1 in the regulation of atherogenesis and the underlying mechanisms. RESULTS: Genetic analyses revealed that coronary artery disease-associated risk variant rs2832227 was associated with BACH1 gene expression in carotid plaques from patients. BACH1 was upregulated in ECs of human and mouse atherosclerotic plaques. Endothelial Bach1 deficiency decreased turbulent blood flow- or western diet-induced atherosclerotic lesions, macrophage content in plaques, expression of endothelial adhesion molecules (ICAM1 [intercellular cell adhesion molecule-1] and VCAM1 [vascular cell adhesion molecule-1]), and reduced plasma TNF-α (tumor necrosis factor-α) and IL-1ß levels in atherosclerotic mice. BACH1 deletion or knockdown inhibited monocyte-endothelial adhesion and reduced oscillatory shear stress or TNF-α-mediated induction of endothelial adhesion molecules and/or proinflammatory cytokines in mouse ECs, human umbilical vein ECs, and human aortic ECs. Mechanistic studies showed that upon oscillatory shear stress or TNF-α stimulation, BACH1 and YAP (yes-associated protein) were induced and translocated into the nucleus in ECs. BACH1 upregulated YAP expression by binding to the YAP promoter. BACH1 formed a complex with YAP inducing the transcription of adhesion molecules. YAP overexpression in ECs counteracted the antiatherosclerotic effect mediated by Bach1-deletion in mice. Rosuvastatin inhibited BACH1 expression by upregulating microRNA let-7a in ECs, and decreased Bach1 expression in the vascular endothelium of hyperlipidemic mice. BACH1 was colocalized with YAP, and the expression of BACH1 was positively correlated with YAP and proinflammatory genes, as well as adhesion molecules in human atherosclerotic plaques. CONCLUSIONS: These data identify BACH1 as a mechanosensor of hemodynamic stress and reveal that the BACH1-YAP transcriptional network is essential to vascular inflammation and atherogenesis. BACH1 shows potential as a novel therapeutic target in atherosclerosis.

PUM2 regulates the formation of thoracic aortic dissection through EFEMP1.

Thoracic aortic dissection (TAD) is a severe cardiovascular disease attributed to the abnormal phenotypic switch of vascular smooth muscle cells (VSMCs). We found that the RNA-binding protein PUM2 and the fibulin protein EFEMP1 were significantly decreased at the TAD anatomical site. Therefore, we constructed expression and silencing vectors for PUM2 and EFEMP1 to analyze differential expression. Overexpression of PUM2 inhibited VSMC proliferation and migration. Western blot analysis indicated that PUM2 overexpression in VSMCs upregulated α-SMA and SM22α and downregulated OPN and MMP2. Immunofluorescence demonstrated that PUM2 and EFEMP1 were co-expressed in VSMCs. Immunoprecipitation confirmed that PUM2 bound to EFEMP1 mRNA to promote EFEMP1 expression. An Ang-II-induced aortic dissection mouse model showed that PUM2 impedes the development of aortic dissection in vivo. Our study demonstrates that PUM2 inhibits the VSMC phenotypic switch to prevent aortic dissection by targeting EFEMP1 mRNA. These findings could assist the development of targeted therapy for TAD.

Treatment of inadvertent cervical arterial catheterization: Single-center experience.

OBJECTIVES: Inadvertent arterial catheterization can occur during transjugular central venous catheter insertion and should be promptly treated to prevent serious consequences. Although many treatment modalities are available, no exist guidelines regarding the selection of treatment. We aimed to describe our experience with the treatment of 11 patients who underwent inadvertent cervical arterial catheterization and propose an algorithm for the selection of treatment methods. METHODS: We retrospectively identified all patients who were treated for inadvertent arterial catheterization at our center between January 2016 and March 2021. We reviewed patient profiles, images, treatment methods, and follow-up data. RESULTS: Eleven patients were included (eight men and three women, age: 36-73 years). Ten catheter misplacements were in the right common carotid artery. The remaining catheter was inserted into the right subclavian artery after penetrating the right common carotid artery. Two catheters were 5-Fr and nine catheters were 11.5-Fr. Two patients underwent manual compressions, three underwent open surgery, three underwent stent-graft repairs, and four underwent Perclose Proglide closure. Clinical success was achieved in all 11 patients. Primary technical success was achieved in 10 patients. In one patient, unsuccessful manual compression was followed by successful stent-graft repair; the manual compression failed to prevent bleeding, possibly because of the long-term oral administration of aspirin for coronary heart disease. The mean follow-up was 5.4 months (range, 1-12 months). The overall mortality rate was zero, and no vascular or neurological events occurred. CONCLUSIONS: The existing data show that the current protocol for the treatment of inadvertent cervical arterial catheterization at our center is safe and effective. However, the data are insufficient and require further clinical validation.

Long-term outcomes of thoracic endovascular repair with quick fenestrater assisted in situ fenestration for type B aortic dissection.

OBJECTIVES: To report the long-term outcomes of patients with type B aortic dissection (TBAD) treated with thoracic endovascular aortic repair (TEVAR) and quick fenestrated (QF)-assisted in situ fenestration (ISF). METHODS: Between October 2017 and December 2018, 15 patients with TBAD requiring revascularization of the supra-aortic trunks underwent TEVAR with QF-assisted ISF at our institution. RESULTS: Thirteen of the 15 patients were male, and the mean age was 52.87 ± 11.26. The technical success rate was 100%. Thirty-day mortality rate was 0. The median follow-up period was 41 months (range, 35-49). During follow-up, one non-aortic-related death was recorded, no fenestration lost its alignment, and no stroke or stent graft migration was observed. Two patients underwent another successful endovascular repair. One case of type Ib endoleak occurred 19 months postoperatively. This was caused by aortic progression distal to the stent graft. Another stent graft with a larger diameter was implanted in the descending aorta. One case of type Ic endoleak was observed 35 months postoperatively. The patient was diagnosed during the annual follow-up without any symptoms. Another bridging stent graft was implanted into the left subclavian artery distal to the already existing one, and the type Ic endoleak was successfully treated. CONCLUSIONS: TEVAR with QF-assisted ISF may be an effective treatment for ISF in type B aortic dissection.

Sorting Nexin 10 Mediates Metabolic Reprogramming of Macrophages in Atherosclerosis Through the Lyn-Dependent TFEB Signaling Pathway.

RATIONALE: SNX10 (sorting nexin 10) has been reported to play a critical role in regulating macrophage function and lipid metabolism. OBJECTIVE: To investigate the precise role of SNX10 in atherosclerotic diseases and the underlying mechanisms. METHODS AND RESULTS: SNX10 expression was compared between human healthy vessels and carotid atherosclerotic plaques. Myeloid cell-specific SNX10 knockdown mice were crossed onto the APOE-/- (apolipoprotein E) background and atherogenesis (high-cholesterol diet-induced) was monitored for 16 weeks. We found that SNX10 expression was increased in atherosclerotic lesions of aortic specimens from humans and APOE-/- mice. Myeloid cell-specific SNX10 deficiency (Δ knockout [KO]) attenuated atherosclerosis progression in APOE-/- mice. The population of anti-inflammatory monocytes/macrophages was increased in the peripheral blood and atherosclerotic lesions of ΔKO mice. In vitro experiments showed that SNX10 deficiency-inhibited foam cell formation through interrupting the internalization of CD36, which requires the interaction of SNX10 and Lyn-AKT (protein kinase B). The reduced Lyn-AKT activation by SNX10 deficiency promoted the nuclear translocation of TFEB (transcription factor EB), thereby enhanced lysosomal biogenesis and LAL (lysosomal acid lipase) activity, resulting in an increase of free fatty acids to fuel mitochondrial fatty acid oxidation. This further promoted the reprogramming of macrophages and shifted toward the anti-inflammatory phenotype. CONCLUSIONS: Our data demonstrate for the first time that SNX10 plays a crucial role in diet-induced atherogenesis via the previously unknown link between the Lyn-Akt-TFEB signaling pathway and macrophage reprogramming, suggest that SNX10 may be a potentially promising therapeutic target for atherosclerosis treatment.

Endovascular and Hybrid Interventions for Extracranial Juxta-Skullbase Carotid Artery Aneurysms: Experience and Long-Term Results.

BACKGROUND: Hybrid and endovascular procedures maybe effective and less invasive alternatives to open surgery for treatment of extracranial carotid artery aneurysm (ECAA), but the optimal management of juxta-skullbase ECAA is controversial. OBJECTIVE: This study evaluated the long-term effects of hybrid and endovascular procedures in treating juxta-skullbase ECAA. METHODS: The records of 9 consecutive patients who underwent hybrid or endovascular interventions for juxta-skullbase ECAA in a single center from April 2014 to May 2020 were retrospectively reviewed. RESULTS: Four patients presented with a pulsating mass, 1 with dysphagia, 1 with pain in the left temporal region, 1 with dizziness and headache, 1 with cerebral infarction, and 1 with dizziness and cerebral infarction. Seven true aneurysms, 1 false aneurysm, and 1 dissecting aneurysm were diagnosed with CTA in the 9 patients (mean age, 50.8±20.3 years; 1 male). The aneurysms were divided into two subgroups: 4 type I, and 5 type IIb according to a recent classification. Per schedule, 7 patients (4 type I and 3 type IIb) were treated with endovascular intervention, and 2 (type IIb) were treated with hybrid procedures. The technique success rate was 88.9%. One patient (type IIb) who was scheduled to be treated with an endovascular procedure was transferred to a hybrid procedure because of failure of the endovascular procedure. Eleven covered stents were implanted to exclude the aneurysms. During follow-up (mean duration 31.2±23.2 months), all aneurysms were proven excluded, no significant complication occurred, and preoperative symptoms resolved. One patient (type I) in the endovascular group had occlusion of the internal carotid artery but no symptoms; the internal carotid artery was patent in the other 8 patients. CONCLUSIONS: Hybrid and endovascular procedures were found effective and durable alternatives to open operation for treatment of extracranial juxta-skullbase carotid aneurysm.

Fra-1 plays a critical role in angiotensin II-induced vascular senescence.

Vascular aging has a strong relationship with cardiovascular disease. Fos-related antigen 1 (Fra-1), also referred to as Fos-like antigen 1, is a transcription factor and has been reported to be involved in many pathologic processes. Here, we demonstrate that Fra-1 plays a critical role in angiotensin II (Ang II)-induced vascular senescence. Fra-1 expression is increased significantly in Ang II-induced rat aortic endothelial cell (RAEC) senescence and the arteries from Ang II-infused mice. Interestingly, silencing Fra-1 blocks Ang II-induced senescence phenotypes in RAECs, including decreased senescence-associated ß-galactosidase staining, and mitigated proliferation suppression and senescence-associated secretory phenotype. Further, knocking down Fra-1 inhibits vascular aging phenotypes in an Ang II-infused mice model. The up-regulated Fra-1 also exists in human atherosclerotic plaques and Ang II-induced vascular smooth muscle cells as well as in replicated senescence RAECs. Mechanistic studies reveal that Fra-1 preferentially associates with c-Jun and binds to the cyclin-dependent kinase inhibitor 1a (p21) and cyclin-dependent kinase inhibitor 2a (p16) promoter region, leading to elevated gene expression, which causes senescence-related phenotypes. In conclusion, our results identify that Fra-1 plays a novel and key role in promoting vascular aging by directly binding and transcriptionally activating p21 and p16 signaling, suggesting intervention of Fra-1 is a potential strategy for preventing aging-associated cardiovascular disorders.-Yang, D., Xiao, C., Long, F., Wu, W., Huang, M., Qu, L., Liu, X., Zhu, Y. Fra-1 plays a critical role in angiotensin II-induced vascular senescence.

Mid-term results of in situ fenestration stented with balloon-expandable bare metal stents during thoracic endovascular aortic repair.

PURPOSE: To assess the safety, feasibility and effectiveness of balloon-expandable bare metal stents (BMS) as bridge stents during thoracic endovascular aortic repair (TEVAR). MATERIALS AND METHODS: Retrospective analysis was conducted on 103 consecutive patients who underwent TEVAR procedures from December 2015 to March 2018. Thirty-one patients fulfilled requirements for inclusion and exclusion in the analysis. Thirty-three in situ fenestration (ISF) procedures (single fenestration [n = 29]; dual fenestration [n = 2]) were performed in the 31 patients (67.7% men; median age, 61.5 year) who underwent TEVAR for thoracic lesions (aortic dissection [n = 23], aortic aneurysm [n = 3], aortic ulcer [n = 5]) with 34 stents (33 balloon-expandable BMS, 1 covered stents) implanted in supraaortic arteries. The success rate of overall intervention, fenestration, and implantation of BMS was recorded. The therapeutic effects and complications during admission and follow-up (median 29.7 months, range 18-45 months) were the primary outcomes. RESULTS: The technical success rate was 90.3% (28/31). All thoracic lesions were totally excluded. Major complications (6.5%) were one dissection in the left subclavian artery (n = 1) and thrombus formation (n = 1). Minor complications (12.9%) were hematoma (n = 1), and type III endoleak (n = 3). During follow-up, no endoleak developed and all fenestrated branch arteries were patent, except for one left subclavian artery dissection and occlusion. CONCLUSIONS: Use of balloon-expandable BMS in ISF is safe and effective in reconstruction of supraarotic arteries during TEVAR.

A Single-Center, Randomized, Controlled Comparison of the Transradial vs Transfemoral Approach for Cerebral Angiography: A Learning Curve Analysis.

Purpose: To compare the characteristics and learning curve of the transfemoral approach (TFA) vs the transradial approach (TRA) for cerebral angiography. Materials and Methods: Between February 2016 and April 2017, 101 patients undergoing cerebral angiography were enrolled. Fifty-one patients (mean age 67 years; 40 men) were randomized to TFA and 50 (mean age 68 years; 41 men) to TRA using a computer-generated random table. The patients' demographic and angiographic data were recorded and analyzed. The learning curve of a novice interventionist was analyzed for procedure time, puncture time, fluoroscopy time, and contrast volume as markers of technical proficiency with TFA compared with TRA. Median values are given with the interquartile range (IQR). Results: Procedure time [35 (IQR 30, 47.5) vs 31.0 (IQR 25.0, 48.9) minutes, p=0.16), fluoroscopy time [10.3 (IQR 7.6, 13.9) vs 9.4 (IQR 6.1, 17.6) minutes, p=0.70], contrast volume [105 (IQR 92, 120) vs 95.5 (IQR 90, 111.3) mL, p=0.13), radiation exposure [390.2 (IQR 268.2, 617.9) vs 455.8 (IQR 286.8, 602.3) mGy, p=0.74], and the number of catheter exchanges [1 (IQR 1, 3) vs 1 (IQR 1, 1), p=0.06] were not significantly different between the TFA and TRA groups, respectively, but puncture time was shorter with TFA than with TRA [0.6 (IQR 0.5, 1.1) vs 1 (IQR 0.6, 1.9) minutes, p=0.01]. The learning curve was steeper with TRA than with TFA in the beginning stages of training, but with increasing experience, the procedure and fluoroscopy times were better for TRA than for TFA. Training progress was made earlier in TRA. Conclusion: TRA is a reasonable alternative to TFA for cerebral angiography. TRA has a shorter learning curve for novice interventionists.

Matrix metalloproteinases are regulated by MicroRNA 320 in macrophages and are associated with aortic dissection.

Aortic dissection (AD) is the circumferential or transversal tear of the aorta wall that allows blood to infiltrate the layers. MicroRNA (miR) analyses have demonstrated a correlation between miR-320 family and AD. The underlying mechanism is yet unclear. The matrix metalloproteinases (MMPs) are a group of proteolytic enzymes that could catalyze the degeneration of the extracellular matrix and the destruction of the vasculature. In this study, we investigated whether miR-320 presented a role in regulating the production of MMPs in aortic dissection. In a cohort of 30 CE patients and 30 healthy controls, the transcription and secretion of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and MMP-12 by monocytes were investigated. The monocyte from AD patients presented significantly elevated capacity of MMP expression than those from healthy controls. In contrast, the monocyte/macrophage expression of miR-320 was significantly lower in AD patients than in controls. In both AD patients and healthy controls, LPS-activation of macrophages resulted in MMP upregulation and miR-320 downregulation, in which the MMP expression was significantly higher while the miR-320 expression was significantly lower in AD patients than in healthy controls. Transfection of miR-320 mimic did not affect MMP gene transcription but significantly reduced the protein production in some MMPs, demonstrated that miR-320 were involved in the post-transcriptional regulation of MMPs. Together, these results demonstrated that miR-320 could regulate the expression of MMPs by macrophages, through which miR-320 may interfere with AD development.

Two-Stage Hybrid Approach for Treatment of Abdominal Aortic Pseudoaneurysm Combined with Superior Mesenteric Artery Occlusion Secondary to Vasculo-Behçet's Disease.

Behçet's disease (BD) is a chronic multisystem autoinflammatory disorder. Multiple arterial involvement in vasculo-BD was extremely rare. A 40-year-old man suffered from abdominal pain and increased lower back pain. He was diagnosed with BD 4 years ago. Computed tomography angiography indicated a 40 mm × 90 mm abdominal aortic saccular pseudoaneurysm and a proximal superior mesenteric artery (SMA) occlusion. We report here a case of successful treatment for abdominal aortic pseudoaneurysm (AAP) and SMA occlusion in a complicated vasculo-BD using 2-stage procedure, including endovascular intervention for AAP and hybrid approach with laparotomy and retrograde canalization and revascularization for SMA occlusion. Retrograde open mesenteric stenting was effective in the treatment of SMA occlusion in patients with vasculo-BD.

Endovascular Therapy of a Giant Renal Artery Aneurysm Combined With High-Flow Renal Arteriovenous Fistula Using a Patent Ductus Arteriosus Occluder.

Renal artery aneurysm (RAA) concomitant with a renal arteriovenous fistula (RAVF) is extremely rare. A 32-year-old man suffered from a giant RAA combined with high-flow RAVF. The computer tomographic angiography (CTA) demonstrated a RAA, which is 6.3 cm in length and 2.1 cm in diameter, combined with an arteriovenous fistula between the right renal artery and right renal vein (fistula area:1.05 cm × 1.0 cm). After a comprehensive preoperative assessment, a patent ductus arteriosus occluder (PDAO) was implanted. At a 1-year follow-up, the CTA study showed that the PDAO was in situ and there was no recanalization of the lesion. At a third-year follow-up, ultrasound examination showed an image of right renal atrophy. The results of long-term follow-up demonstrate that PDAO is safe and effective for the management of RAAs combined with high-flow RAVF.

Ring-Stripping Retrograde Endarterectomy for Treatment of Common Carotid Artery Occlusion: A Minimally Invasive, Effective Procedure.

BACKGROUND: To evaluate the efficacy and safety of in situ ring-stripping retrograde carotid endarterectomy (IS-RRCEA) in long-segment, symptomatic, chronic common carotid artery occlusion (CCAO). METHODS: Thirty-nine patients (24 men; 15 women) with symptomatic chronic CCAO who underwent IS-RRCEA in our center were included retrospectively. The mean age of the men was significantly less than that of the women (59.6 ± 5.8 vs. 67.8 ± 6.3 years; P < 0.001). Risk factors, clinical characteristics, and CCAO classification of patients and effectiveness and safety of IS-RRCEA were analyzed. RESULTS: Patients presented with the following symptoms: dizziness (6; 15.4%), transient ischemic attack (TIA; 33; 84.6%), and decreased vision (15; 38.5%). IS-RRCEA was performed on the left side in 25 (64.1%) cases and on the right side in 14 (35.9%) cases. The technical success rate of the procedure was 100%. Cerebral perfusion on the ipsilateral site improved in all patients. In the postoperative period, stroke and myocardial infarction occurred in one patient, and recurrent laryngeal nerve damage occurred in another; these patients' symptoms mostly resolved except for residual paresis in the stroke patient. Thirty-eight patients (97.4%) were followed for a mean of 29 ± 13.3 months after the IS-RRCEA; in 1-year follow-up, 31 patients (31/33; 93.9%) with preoperative TIA have had no TIAs; 2 patients (2/33; 6.1%) have fewer TIAs. Two patients (2/6; 33.3%) with preoperative dizziness have had no dizziness, and 4 (4/6; 66.7%) have had fewer episode of dizziness, no recurrent stenosis (>50%), or recognized occlusion. CONCLUSIONS: Our single-center experience indicates that IS-RRCEA is an effective treatment for selected types of CCAO. Studies of the operation in larger populations with longer term follow-up should be conducted.

A Novel Reverse Branch Technique for Reconstruction of a Renal Artery Perfused by the False Lumen After Thoracic Endovascular Aortic Repair.

PURPOSE: To describe an innovative endovascular technique that successfully reconstructs a renal artery completely perfused by the false lumen after thoracic endovascular aortic repair (TEVAR). CASE REPORT: A 65-year-old patient diagnosed with acute Stanford type B aortic dissection underwent successful TEVAR 4 years ago. Regular follow-up found that the thoracic aorta was well repaired, but the false lumen in the abdominal aorta had enlarged year by year. The left renal artery was supplied entirely by the false lumen, which caused kidney hypoperfusion. The abdominal aorta was successfully remodeled using endovascular aneurysm repair with reconstruction of the left renal artery using Viabahn stent-grafts inserted through the patent false lumen. At 6 months, computed tomography showed false lumen thrombosis and patent Viabahn stent-grafts in the false lumen. CONCLUSION: The false lumen reverse branch technique was feasible in our case, which provides a new idea for dealing with distal dissection involving the renovisceral arteries after TEVAR.

Heat shock protein 27 plays a protective role in thoracic aortic dissection by promoting cell proliferation and inhibiting apoptosis.

BACKGROUND: Thoracic aortic dissection (TAD) is one of the most severe aortic diseases. The study aimed to explore the potential role of heat shock protein 27 (HSP27) in the pathogenesis of TAD using an in vitro model of oxidative stress in vascular smooth muscle cells (VSMCs). METHODS: HSP27 was analyzed in aortic surgical specimens from 12 patients with TAD and 8 healthy controls. A lentiviral vector was used to overexpress HSP27 in rat aortic VSMCs. Cell proliferation and apoptosis were measured under oxidative stress induced by H2O2. RESULTS: HSP27 expression was significantly higher in aortic tissue from patients with TAD and VSMCs in the aortic media were the main cell type producing HSP27. Elevated oxidative stress was also detected in the TAD samples. Overexpression of HSP27 significantly attenuated H2O2-induced inhibition of cell proliferation. Furthermore, HSP27 was found to decrease H2O2-induced cell apoptosis and oxidative stress. CONCLUSIONS: These results suggest that HSP27 expression promotes VSMC viability, suppresses cell apoptosis, and confers protection against oxidative stress in TAD.

Quercitrin treatment protects endothelial progenitor cells from oxidative damage via inducing autophagy through extracellular signal-regulated kinase.

Atherosclerosis is a disease resulting from impaired endothelial function, often caused by oxidant injury or inflammation. Endothelial progenitor cells (EPCs) play a critical role in repairing damaged endothelium and protecting against atherosclerosis. Quercitrin, a plant-derived flavonoid compound, displays antioxidant and anti-inflammatory activities. In this study, we showed that quercitrin treatment reduced the apoptosis of EPCs caused by oxidized low-density lipoprotein (ox-LDL) in a dose-dependent manner. Quercitrin improved tube formation, migration and adhesion of ox-LDL-treated EPCs. To determine the effect of quercitrin in vivo, EPCs treated with or without ox-LDL and quercitrin were locally injected into the ischemic hind limb muscle of nude mice. Those injected with EPCs treated with ox-LDL and quercitrin showed significantly increased local accumulation of EPCs, blood flow recovery and capillary density compared with the control and ox-LDL only groups. Furthermore, we showed that quercitrin enhanced autophagy and upregulated mitogen-activated protein kinase and ERK phosphorylation in a dose-dependent manner in vitro. Autophagy inhibitors, chloroquine and 3-methyladenine, abrogated quercitrin-enhanced autophagy caused by ox-LDL as evidenced by decreased numbers of branch points, migratory cells and adherent cells, and increased numbers of apoptotic cells. The ERK inhibitor PD98059 abrogated quercitrin-enhanced autophagy, as identified by decreased autophagosome formation and downregulated ERK phosphorylation. The inhibition of ERK did not affect the expression of Rac1, but enhanced phosphorylation of Akt. Quercitrin treatment also increased the expression of E-cadherin, and PD98059 abrogated the upregulation of E-cadherin induced by quercitrin. Our findings suggested that autophagy is a protective mechanism in EPCs exposed to oxidative damage. Quercitrin can promote autophagy through the activation of ERK and the ERK signaling pathway is therefore thought to play a pivotal role in mediating the protective effects on EPCs.

Endovascular repair of proximal para-anastomotic aneurysms after previous open abdominal aortic aneurysm reconstruction.

OBJECTIVE: To evaluate the safety, efficacy and durability of endovascular repair for proximal para-anastomotic aneurysms after previous open abdominal aortic aneurysms prosthetic reconstruction and share our experience. METHODS: We retrospectively reviewed the data of all patients with previous open abdominal aortic aneurysms prosthetic reconstruction who underwent endovascular repair for proximal para-anastomotic aneurysms between May 2003 and January 2013 in our center (Nuremberg South Hospital). Key clinical outcomes included technical success rate, peri-operative morbidity and mortality, mid-term complications, reinterventions and open conversion rates. RESULTS: Totally, 24 patients of proximal para-anastomotic aneurysm were treated by endovascular repair. Successful deployments of stent graft were achieved in all patients (100%). Median hospital stay was 6.7 days. One patient had minor type Ia endoleak and one patient developed wound infection. There were no early open conversions and deaths. During a median follow-up of 43 months (range, 7-67 months), computed tomography angiography revealed type Ia endoleaks in four patients (16.7%). The overall reintervention and open conversion rates during follow-up were 16.7% (4/24) and 4.2% (1/24), respectively. Estimates of freedom from reintervention were 91.7% at 1 year, 87.1% at 3 years and 80.9% at 5 years. There was significant difference in freedom from reintervention between proximal para-anastomotic aneurysms patients treated with tube and unibody bifurcated stent grafts (p = 0.034). The cumulative mortality rate was 12.5% (3/24), actuarial analysis for all patients estimated survival rates of 95.8% at 1 year and 87.3% at 5 years. CONCLUSIONS: Proximal para-anastomotic aneurysms are severe complications after abdominal aortic aneurysm open reconstruction. Closer follow-up and prompt treatment are necessary. Endovascular treatment for proximal para-anastomotic aneurysms is effective, safe and durable. Unibody bifurcated stent graft proved to be suitable for most proximal para-anastomotic aneurysms with various anatomical features.