Outcomes of standard EVAR for juxtarenal abdominal aortic aneurysm in patients unsuitable for fenestrated EVAR and open repair.

OBJECTIVE: To evaluate the long-term outcomes of standard endovascular aneurysm repair (S-EVAR) of juxtarenal abdominal aortic aneurysms (JAAAs). METHODS: Data of patients with JAAAs who were unsuitable for fenestrated endovascular aneurysm repair (F-EVAR) and open repair (OR) and underwent treatment from January 2015 to December 2021 were retrospectively reviewed. Computed tomography angiography and ultrasonography of the aorta were performed before discharge, at 6 and 12 months postoperatively, and annually thereafter. The main outcome measures were mortality, type Ia endoleaks, and reintervention. RESULTS: A total of 62 patients (mean age, 72.1 ± 7.3 years) underwent S-EVAR. The mean aneurysm length and diameter and the proximal neck length and diameter were 110.4 ± 30.9 mm, 57.2 ± 15.9 mm, 8.09 ± 0.97 mm, and 26.05 ± 0.49 mm, respectively. The mean suprarenal and infrarenal aortic angles were 162.9 ± 26° and 144.1 ± 31°, respectively. The mean follow-up duration was 40.6 ± 23.4 months and the 5-year survival rate was 62.2%. Six (9.8%) patients experienced type Ia endoleaks, of whom three underwent endovascular repair at 12, 18, and 24 months, one underwent conversion to OR for AAA rupture at 7 days and died, two had minor endoleaks and were kept under observation, and one declined reintervention at 36 months. The 5-year freedom from reintervention rate was 84.4%. The aneurysm diameter shrank in 50 cases (81%), remained stable in 5 cases (8%), and increased in 7 cases (11.3%). A suprarenal aortic angle <114° was associated with type Ia endoleak (p = .005). CONCLUSIONS: In patients unsuitable for F-EVAR and OR and with a suprarenal aortic angle >114°, the use of S-EVAR for JAAAs can be considered safe and effective. In this study, early and long-term postoperative outcomes demonstrated that S-EVAR achieved satisfactory results in the prevention of aneurysm rupture and associated mortality.

The oxidized phospholipid PGPC impairs endothelial function by promoting endothelial cell ferroptosis via FABP3.

Ferroptosis is a novel cell death mechanism that is mediated by iron-dependent lipid peroxidation. It may be involved in atherosclerosis development. Products of phospholipid oxidation play a key role in atherosclerosis. 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) is a phospholipid oxidation product present in atherosclerotic lesions. It remains unclear whether PGPC causes atherosclerosis by inducing endothelial cell ferroptosis. In this study, human umbilical vein endothelial cells (HUVECs) were treated with PGPC. Intracellular levels of ferrous iron, lipid peroxidation, superoxide anions (O2•-), and glutathione were detected, and expression of fatty acid binding protein-3 (FABP3), glutathione peroxidase 4 (GPX4), and CD36 were measured. Additionally, the mitochondrial membrane potential (MMP) was determined. Aortas from C57BL6 mice were isolated for vasodilation testing. Results showed that PGPC increased ferrous iron levels, the production of lipid peroxidation and O2•-, and FABP3 expression. However, PGPC inhibited the expression of GPX4 and glutathione production and destroyed normal MMP. These effects were also blocked by ferrostatin-1, an inhibitor of ferroptosis. FABP3 silencing significantly reversed the effect of PGPC. Furthermore, PGPC stimulated CD36 expression. Conversely, CD36 silencing reversed the effects of PGPC, including PGPC-induced FABP3 expression. Importantly, E06, a direct inhibitor of the oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine IgM natural antibody, inhibited the effects of PGPC. Finally, PGPC impaired endothelium-dependent vasodilation, ferrostatin-1 or FABP3 inhibitors inhibited this impairment. Our data demonstrate that PGPC impairs endothelial function by inducing endothelial cell ferroptosis through the CD36 receptor to increase FABP3 expression. Our findings provide new insights into the mechanisms of atherosclerosis and a therapeutic target for atherosclerosis.

Pterostilbene alleviates abdominal aortic aneurysm via inhibiting macrophage pyroptosis by activating the miR-146a-5p/TRAF6 axis.

Pterostilbene (PTE), a natural stilbene found in blueberries and several varieties of grapes, has several pharmacological activities, including anti-inflammatory and antioxidative activities. However, its role in abdominal aortic aneurysm (AAA), which is a severe inflammatory vascular disease, remains incompletely understood. In this study, we investigated the protective effects of natural stilbene PTE on AAA formation and the underlying mechanism. Two AAA mouse models (Ang II-induced model and PPE-induced model) were used to examine the effect of PTE on AAA formation. We showed that PTE administration attenuated AAA formation in mice. Furthermore, we found that PTE significantly inhibited inflammatory responses in mouse aortas, as PTE suppressed macrophage pyroptosis and prevented macrophage infiltration in aortas, resulting in reduced expression of pro-inflammatory cytokines in aortas. We also observed similar results in LPS + ATP-treated Raw 264.7 cells (a macrophage cell line) and primary peritoneal macrophages in vitro. We showed that pretreatment with PTE restrained inflammatory responses in macrophages by inhibiting macrophage pyroptosis. Mechanistically, miR-146a-5p and TRAF6 interventions in vivo and in vitro were used to investigate the role of the miR-146a-5p/TRAF6 axis in the beneficial effect of PTE on macrophage pyroptosis and AAA. We found that PTE inhibited macrophage pyroptosis by miR-146a-5p-mediated suppression of downstream TRAF6 expression. Moreover, miR-146a-5p knockout or TRAF6 overexpression abrogated the protective effect of PTE on macrophage pyroptosis and AAA formation. These findings suggest that miR-146a-5p/TRAF6 axis activation by PTE protects against macrophage pyroptosis and AAA formation. PTE might be a promising agent for preventing inflammatory vascular diseases, including AAA.

Microarray Expression Profile and Bioinformatic Analysis of Circular RNA in Human Arteriosclerosis Obliterans.

Background: Arteriosclerosis obliterans (ASO) is the leading cause of nontraumatic lower-extremity amputations. Multiple researches have suggested that circular RNAs (circRNAs) played vital regulatory functions in cancer and cardiovascular disease. Nevertheless, the underlying effect and pathological mechanism of circRNAs in the formation and progression of ASO are still indistinct. Methods and Results: This study used microarray analysis to investigate the expression portrait of circRNAs in normal lower extremity arteries and ASO arteries. Bioinformatics analysis was conducted using the KEGG database to study the enrichment of differentially expressed circRNAs (DE circRNAs) and predict their functions. The accuracy of microarray assay was verified by evaluating expression of the top 5 upregulated and 5 downregulated circRNAs (raw density of normal group ≥200) using RT-qPCR. A circRNA-miRNA-mRNA interaction network was further predicted using software. Compared to the normal lower extremity group, the ASO arteries with HE and EVG staining presented hyperplastic fibrous membrane and luminal stenosis. A total of 12,735 circRNAs were identified, including 1196 DE circRNAs with 276 upregulated and 920 downregulated in ASO group based on |log2(FC)| > 1 and padj < 0.05. Among selected 10 circRNAs, RT-qPCR confirmed that hsa_circ_0003266, hsa_circ_0118936 and hsa_circ_0067161 were upregulated while hsa_circ_0091934 and hsa_circ_0092022 were downregulated in ASO group (p < 0.05). GO analysis presented that the DE circRNAs were primarily enriched in protein binding, intracellular part and organelle organization. KEGG pathway analysis indicated that MAPK signaling pathway, human T-cell leukemia virus 1 infection, proteoglycans in cancer were associated with the DE circRNAs. The circRNA-miRNA-mRNA interactive network revealed that both mRNAs and miRNAs linked to circRNAs played an indispensable role in ASO. Conclusion: This study described the expression portrait of circRNAs in human ASO arteries, and revealed the molecular background for further investigations of the circRNA regulatory mechanism in the formation and progression of ASO.

Clinical characteristics and therapeutic strategy for patients with spontaneous isolated abdominal aortic dissection.

Objective: Spontaneous isolated abdominal aortic dissection (SIAAD) is a rare aortic emergency and not yet fully understood. This study aims to report the characteristics and treatments of 31 patients with SIAAD in the past 12 years. Methods: A total of 31 consecutive patients with SIAAD between 2010 and 2022 were included. The clinical manifestations, treatment strategies, and outcomes were reviewed. Following the SVS/STS reporting standard, we compared the clinical characteristics with different locations of primary entry, or different numbers of dissected zones. Furthermore, we compared the effects of surgical and conservative therapies on the outcome during the follow-up. Results: Among the 31 patients with SIAAD, 16 (51.6%) were in the acute phase on admission. The primary entry of SIAAD was mainly located in Zone 9 (67.7%). Most patient presented with dissection involving 1 or 2 aortic zones (61.3%). In addition, 35.5% and 64.5% of SIAADs involved the visceral and iliac arteries, respectively. Compared with asymptomatic SIAADs, the symptomatic ones had longer dissection lengths (P = 0.008) and tended to involve iliac artery more frequently (P = 0.098). There were differences in the number of dissected aortic zones (P = 0.005) among patients with primary entry located in Zone 5 (Supraceliac aorta), Zone 6-8 (Paravisceral aorta) and Zone 9 (Infrarenal aorta). The involvement of visceral artery (P = 0.039) and iliac artery (P = 0.006) was significantly different between the subgroups of SIAAD involving one, two, and three or more aortic zones. The cumulative incidence of adverse false lumen progression events was significantly lower (P = 0.000) and the rate of false lumen thrombogenesis or disappearance was higher in patients receiving surgery (P = 0.001). The cumulative all-cause mortality was 9.7% at 1-year, and 19.7% at 5-year, with no significant difference between surgical and conservative therapies. Conclusions: Clinical features of SIAAD vary depending on the location of the primary entry and the number of dissected aortic zones. Although surgery was not associated with a lower all-cause mortality compared with conservative therapy, it was associated with a lower incidence of adverse false lumen progression and a higher rate of aortic remodeling.

Improving the Initial Coulombic Efficiency of Sodium-Storage Antimony Anodes via Electrochemically Alloying Bismuth.

Improving cycling stability while maintaining a high initial Coulombic efficiency (ICE) of the antimony (Sb) anode is always a trade-off for the design of electrodes of sodium-ion batteries (SIBs). Herein, we prepare a carbon-free Sb8Bi1 anode with an ICE of 87.1% at 0.1 A g-1 by a one-step electrochemical reduction of Sb2O3 and Bi2O3 in alkaline solutions. The improved ICE of the Sb8Bi1 anode is due to the alloying of bismuth (Bi) that prevents irreversible interfacial reactions during the sodiation process. Unlike carbon buffers, the use of Bi will reduce the number of side reactions between the carbon buffer and sodium. Moreover, Bi2O3 can promote the reduction of Sb2O3 and reduce the particle size of Sb from ∼20 µm to below 300 nm. The electrolytic products can be modulated by controlling the cell voltages and electrolysis time. The electrolytic Sb8Bi1 anode delivered a capacity of 625 mAh g-1 after 200 cycles with an ICE of 87.1% at 0.1 A g-1 and even 625 mAh g-1 at 1 A g-1 over 100 cycles. Hence, alloying Bi into Sb is an effective way to make a long-lasting Sb anode while maintaining a high Coulombic efficiency.

SMYD2 regulates vascular smooth muscle cell phenotypic switching and intimal hyperplasia via interaction with myocardin.

The SET and MYND domain-containing protein 2 (SMYD2) is a histone lysine methyltransferase that has been reported to regulate carcinogenesis and inflammation. However, its role in vascular smooth muscle cell (VSMC) homeostasis and vascular diseases has not been determined. Here, we investigated the role of SMYD2 in VSMC phenotypic modulation and vascular intimal hyperplasia and elucidated the underlying mechanism. We observed that SMYD2 expression was downregulated in injured carotid arteries in mice and phenotypically modulated VSMCs in vitro. Using an SMC-specific SMYD2 knockout mouse model, we found that SMYD2 ablation in VSMCs exacerbated neointima formation after vascular injury in vivo. Conversely, SMYD2 overexpression inhibited VSMC proliferation and migration in vitro and attenuated arterial narrowing in injured vessels in mice. SMYD2 downregulation promoted VSMC phenotypic switching accompanied with enhanced proliferation and migration. Mechanistically, genome-wide transcriptome analysis and loss/gain-of-function studies revealed that SMYD2 up-regulated VSMC contractile gene expression and suppressed VSMC proliferation and migration, in part, by promoting expression and transactivation of the master transcription cofactor myocardin. In addition, myocardin directly interacted with SMYD2, thereby facilitating SMYD2 recruitment to the CArG regions of SMC contractile gene promoters and leading to an open chromatin status around SMC contractile gene promoters via SMYD2-mediated H3K4 methylation. Hence, we conclude that SMYD2 is a novel regulator of VSMC contractile phenotype and intimal hyperplasia via a myocardin-dependent epigenetic regulatory mechanism.

High-density lipoprotein regulates angiogenesis by long non-coding RNA HDRACA.

Normal high-density lipoprotein (nHDL) can induce angiogenesis in healthy individuals. However, HDL from patients with coronary artery disease undergoes various modifications, becomes dysfunctional (dHDL), and loses its ability to promote angiogenesis. Here, we identified a long non-coding RNA, HDRACA, that is involved in the regulation of angiogenesis by HDL. In this study, we showed that nHDL downregulates the expression of HDRACA in endothelial cells by activating WW domain-containing E3 ubiquitin protein ligase 2, which catalyzes the ubiquitination and subsequent degradation of its transcription factor, Kruppel-like factor 5, via sphingosine 1-phosphate (S1P) receptor 1. In contrast, dHDL with lower levels of S1P than nHDL were much less effective in decreasing the expression of HDRACA. HDRACA was able to bind to Ras-interacting protein 1 (RAIN) to hinder the interaction between RAIN and vigilin, which led to an increase in the binding between the vigilin protein and proliferating cell nuclear antigen (PCNA) mRNA, resulting in a decrease in the expression of PCNA and inhibition of angiogenesis. The expression of human HDRACA in a hindlimb ischemia mouse model inhibited the recovery of angiogenesis. Taken together, these findings suggest that HDRACA is involved in the HDL regulation of angiogenesis, which nHDL inhibits the expression of HDRACA to induce angiogenesis, and that dHDL is much less effective in inhibiting HDRACA expression, which provides an explanation for the decreased ability of dHDL to stimulate angiogenesis.

Ultrasound-guided intraoperative inferior vena cava stent implantation for treatment of acute hypotension during orthotopic liver transplantation.

Severe obstruction of inferior vena cava (IVC) outflow after orthotopic liver transplantation can result in persistent hypotension, leading to transplantation failure and intraoperative circulatory instability and can even threaten the patient's life. IVC stent implantation is a therapeutic approach to relieve the obstruction of IVC outflow. In the present report, we describe two cases of IVC stent implantation assisted by color Doppler ultrasound during orthotopic liver transplantation to manage the persistent hypotension caused by acute obstruction of IVC outflow. At 1 and 3 months of follow-up, the stent position was optimal, and the stent and IVC patency were satisfactory without thrombosis.

SMYD2 Regulates Vascular Smooth Muscle Cell Phenotypic Switching and Intimal Hyperplasia via Interaction with Myocardin.

The SET and MYND domain-containing protein 2 (SMYD2) is a histone lysine methyltransferase that has been reported to regulate carcinogenesis and inflammation. However, its role in vascular smooth muscle cell (VSMC) homeostasis and vascular diseases has not been determined. Here, we investigated the role of SMYD2 in VSMC phenotypic modulation and vascular intimal hyperplasia and elucidated the underlying mechanism. We observed that SMYD2 expression was downregulated in injured carotid arteries in mice and phenotypically modulated VSMCs in vitro. Using a SMC-specific Smyd2 knockout mouse model, we found that Smyd2 ablation in VSMCs exacerbates neointima formation after vascular injury in vivo. Conversely, Smyd2 overexpression inhibits VSMC proliferation and migration in vitro and attenuates arterial narrowing in injured vessels in mice. Smyd2 downregulation promotes VSMC phenotypic switching accompanied with enhanced proliferation and migration. Mechanistically, genome-wide transcriptome analysis and loss/gain-of-function studies revealed that SMYD2 up-regulates VSMC contractile gene expression and suppresses VSMC proliferation and migration, in part, by promoting expression and transactivation of the master transcription cofactor myocardin. In addition, myocardin directly interacts with SMYD2, thereby facilitating SMYD2 recruitment to the CArG regions of SMC contractile gene promoters and leading to an open chromatin status around SMC contractile gene promoters via SMYD2-mediated H3K4 methylation. Hence, we conclude that SMYD2 is a novel regulator of VSMC contractile phenotype and intimal hyperplasia via a myocardin-dependent epigenetic regulatory mechanism and may be a potential therapeutic target for occlusive vascular diseases.

Press-N-Go On-Skin Sensor with High Interfacial Toughness for Continuous Healthcare Monitoring.

On-skin electronic sensors are demanded for healthcare monitoring such as the continuous recording of biopotential and motion signals from patients. However, the mechanical mismatches and poor interface adhesion at the skin/sensor interfaces always cause high interfacial impedance and artifacts, frequent interfacial failure, and unexpected depletion of the device, which significantly limit the performance of the sensors. We here develop an on-skin sensor based on a conductive pressure-sensitive tape, which is assembled from supramolecular dual-cross-linked hydrogel composites. Both covalent and noncovalent cross-links in the hydrogel networks could harvest high flexibility, pressure-sensitive adhesion, and high interfacial toughness altogether, enabling a convenient "Press-N-Go" application of the sensor on human skin without additional pre/post-treatment on the skin or the senor. The high conformability and low resistivity of the tape can sustainably lower the interfacial impedance and thus improve signal quality in various measurement conditions. Our design provides a feasible path to develop interface-toughened on-skin electronics, which is desired in dynamic human-machine interfaces.

The Influencing Factors and Prognostic Evaluation in the Treatment Decisions for Acute and Subacute Nondissection-Related Superior Mesenteric Artery Thromboembolism.

BACKGROUND: The unclarified treatment strategy for acute and subacute ndSMA-TE limits the therapeutic efficacy and worsens the prognosis. This study aimed to determine the predictive factors impacting the treatment strategy for acute and subacute ndSMA-TE. METHOD: A database of 116 patients with nonchronic ndSMA-TE admitted between January 2001 and December 2021 was retrospectively analyzed. Univariate/multivariate logistic regression and the predictive models constructed by stepwise backward regression were used to explore the influencing factors of the treatment decisions and the risk factors for failed conservative treatment. The EuroQol-5 Dimension questionnaire was used to evaluate the long-term quality of life. RESULTS: Only the white blood cell (WBC) levels were significantly different between the conservative group and the surgical group (P = 0.013 < 0 .05, odds ratio (OR) = 1.153, 95% confidence interval (CI) [1.038, 1.306]). The WBC levels (P < 0.001, OR = 1.169, 95% CI [1.080, 1.286]) and heart diseases (except atrial fibrillation) (P = 0.011 < 0 .05, OR = 5.116, 95% CI [1.541, 20.452]) were included in the predictive model of the treatment decision. The hemoglobin levels (P = 0.005 < 0 .05, OR = 1.095, 95% CI [1.040, 1.187]) and no flatus or stool (P = 0.007 < 0 .05, OR = 0.031, 95% CI [0.002, 0.296]) were significant risk factors for the conservative treatment outcome. The EuroQol-5 Dimension evaluation demonstrated a fairly high long-term quality of life in both treatment strategies. CONCLUSIONS: Elevated WBC levels, decreased hemoglobin levels, and no flatus or stool can be used as predictive indicators for the surgical treatment of nonchronic ndSMA-TE to avoid a misdiagnosis and an inappropriate treatment.

Prognosis and Remodeling after Endovascular Repair for Acute, Subacute, and Chronic Type B Aortic Dissection.

PURPOSE: Thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD) is already well introduced, but the best time point to perform TEVAR has not been defined. This study was to report mid- to long-term outcomes and aortic remodeling of TEVAR in patients with TBAD. MATERIALS AND METHODS: In total, 318 TBAD patients from June 2001 to May 2016 were retrospectively reviewed. Patients were divided into 3 groups depending on interval between dissection onset to TEVAR: acute (0-7 days), subacute (8-30 days), and chronic (>30 days). Clinical and morphological data were collected and analyzed. RESULTS: The follow-up aorta-related mortality rates in the 3 groups were 17.6%, 2.6%, 4.2%, and the proximal stent-induced new entry rates were 11.8%, 1.6%, 2.8%, respectively. Aortic remodeling was satisfied in both the acute and subacute group, but the false lumen diameter did not decrease (p>0.05) in the chronic group. Compared with the VIRTUE classification (acute, 0-14 days; subacute, 15-92 days; chronic, >92 days), mid- to long-term outcomes of patients within the first overlapped interval between the 2 classifications (8-14 days) were similar to that of subacute patients (15-30 days), while aortic remodeling of patients in the second overlapped interval (31-92 days) was similar to that of chronic patients (>92 days). CONCLUSIONS: This study suggests that TEVAR for subacute TBAD is associated with a low long-term rate of aorta-related death. Aortic remodeling of chronic dissections is not satisfactory. Additional results suggest that the subacute phase (8-30 days) may be the optimal time to perform TEVAR for uncomplicated TBAD.

Current Perspective and Strategy on Management of Spontaneous Jugular Venous Ectasia: A Systematic Review.

BACKGROUND: Spontaneous jugular venous ectasia (SJVE) is characterized by dilation of the internal jugular vein (IJV) and external jugular vein. It is generally considered a benign anomaly. There is no accepted categorization for this disorder. METHODS: We conducted a case series study and a systematic review of available articles on SJVE to understand the main characteristics, clinicopathologic classifications, and therapeutic approaches. RESULTS: From January 2001 to December 2021, 14 patients in our hospital were analyzed. A total of 110 original articles (295 cases/311 lesions) were included in the systematic review. We proposed a classification and categorized SJVE into 4 main types (type I-IV) plus one (type V) in which the specific ectasia was located around the jugular bulb at the IJV. CONCLUSIONS: Conservative treatment is preferred for patients with type I (without thrombus) SJVE and asymptomatic patients who can be treated without anticoagulants. The therapeutic efficiency of surgery was high, and the best surgical modalities were chosen according to the type of SJVE.

Comparisons of outcomes of open surgery versus endovascular intervention for thrombotic popliteal artery aneurysm with acute lower limb ischemia: a systematic review.

BACKGROUND: Thrombotic popliteal artery aneurysm (PAA) with acute lower limb ischemia (ALI) is a serious disease leading to amputation. The choice of emergency procedures is not clearly defined, and the difference in therapeutic efficiency between open surgery and endovascular intervention is still unclear. METHOD: We conducted a comprehensive search through PubMed, Wiley Online Library and ScienceDirect. According to the predefined inclusion and exclusion criteria, eligible articles were screened out, and all relevant data were extracted for further analysis. Our study was designed and developed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guideline. We critically assessed all included articles by Joanna Briggs Institute (JBI) Critical Appraisal Checklists and the Methodological Index for Non-Randomized Studies (MINORS). RESULT: A total of 29 articles (1338 patients/1387 limbs) were included in the study. After a 1-year follow-up, the primary patency rate of the open surgery group was significantly lower than that of the endovascular intervention group (72.65 vs. 81.46%, P = 0.004), but without significant difference in the secondary patency rate (86.19 vs. 86.86%, P = 0.825). The limb salvage rate of the open surgery group was also significantly lower (83.07 vs. 98.25%, P < 0.001). After the 2-year follow-up, the primary patency rate of the open surgery group was still significantly lower (48.57 vs. 59.90%, P = 0.021). CONCLUSION: The outcome of endovascular intervention was better than that of open surgery especially in the 1-year limb salvage rate and primary patency rate at the 1-year and 2-year follow-ups.

CircCRIM1 Ameliorates Endothelial Cell Angiogenesis in Aging through the miR-455-3p/Twist1/VEGFR2 Signaling Axis.

Background: Aging leads to vascular endothelial cell senescence. Decreased expression of VEGFA and VEGFR2 plays a crucial role in impairing angiogenesis in senescent endothelial cells. Noncoding RNAs, including circular RNAs (circRNAs) and microRNAs (miRNAs), regulate endothelial cell proliferation, differentiation, apoptosis, and migration and participate in the occurrence and development of vascular diseases. However, the mechanism of noncoding RNAs in age-related vascular endothelial dysfunction remains unclear. Here, we aimed to identify the circRNA that is associated with VEGF/VEGFR2 signaling pathway activation in angiogenesis. Methods: Immunoblotting, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), in vitro and in vivo experiments, luciferase assays, and chromatin immunoprecipitation followed by qRT-PCR (ChIP-qPCR) assays were performed to clarify the roles played by circCRIM1 in mouse aortic endothelial cell (MAEC) angiogenesis. Results: CircCRIM1 expression was downregulated in both an aging mouse model of lower limb ischemia in vivo and aging MAECs in vitro. Overexpressing circCRIM1 mediated through a plasmid or adeno-associated virus (AAV) reversed the downregulation of angiogenesis-related phenotype acquisition during aging. MiR-455-3p was confirmed to be a potential target of circCRIM1 through luciferase assays followed by RNA fluorescence in situ hybridization (FISH), which revealed the colocalization of circCRIM1 and miR-455-3p. CircCRIM1 was found to be a competitive endogenous RNA that sponged miR-455-3p and regulated angiogenesis-related phenotypes in MAECs. Furthermore, Twist1 was found to be downstream of miR-455-3p. A ChIP-qPCR assay showed that Twist1 promoted VEGFR2 expression by binding to the promoter region, playing a vital role in angiogenesis. Conclusions: Decreased expression of circCRIM1 impaired angiogenesis in aging via the miR-455-3p/Twist1/VEGFR2 axis. Our findings suggest that overexpression of circCRIM1 may be an effective therapeutic strategy for promoting ischemic lower limb blood flow recovery.

Intervention time decides the status of autophagy, NLRP3 activity and apoptosis in macrophages induced by ox-LDL.

BACKGROUND: It has been determined through extensive studies that autophagy, the Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome and apoptotic responses in macrophages jointly contribute to atherogenesis and its development in the presence of lipid abnormalities. Few studies have investigated in full-scale if the intervention time for lipids abnormality or NLRP3 activation have a significant effect on autophagy, NLRP3 or the apoptotic status in macrophages. METHODS: Human THP-1 monocyte-derived macrophages were established by challenging THP-1 monocytes with 80 µg/ml oxidized low-density lipoprotein (ox-LDL) for specific durations. Foam cell formation was observed by Oil Red O (ORO) staining. Western blots were employed to determine protein expression. Transmission electron microscope (TEM) and immunofluorescence microscopy were applied to observe the autophagic status of cells. Cell apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). RESULTS: The cells were treated with ox-LDL for 12 h and 36 h, which were considered to represent early and advanced stages of atherogenesis for this study. The results showed that inhibition of ox-LDL phagocytosis by cytochalasin D in the early stage improved autophagic status, reduced NLRP3 activation and the apoptotic response significantly. In contrast, cytochalasin D had little effect on blocking the detrimental effect of ox-LDL at the advanced stage. Moreover, the changes in autophagy, apoptosis and NLRP3 expression after treatment with small interfering (si) RNA targeting NLRP3 in the early and advanced stages of atherogenesis were consistent with the above data. CONCLUSIONS: Interventions against lipid disorders or inflammatory reactions in the early or advanced stages of atherogenesis may have different results depending on when they are applied during the process of atherosclerotic pathogenesis. These results may help improve therapeutic strategies for atherosclerosis prevention. Furthermore, a healthy lifestyle should still be recommended as the most important and inexpensive measure to prevent atherogenesis.

Stent patency rates and prognostic factors of endovascular intervention for iliofemoral vein occlusion in post-thrombotic syndrome.

OBJECTIVE: Post-thrombotic syndrome (PTS), an important complication of deep venous thrombosis (DVT), adversely affects patients' quality of life. Endovascular intervention in PTS can relieve symptoms rapidly with high therapeutic value. This study mainly focuses on how to improve postoperative stent patency rates and aims to find prognostic factors impacting patency. METHODS: According to the specific inclusion and exclusion criteria, PTS patients who underwent endovascular intervention at the First Affiliated Hospital of Sun Yat-sen University from December 1, 2014, to December 31, 2019, were included in this single-center prospective study. Follow-up data were collected and analyzed regularly over 2 years. RESULTS: Overall, 31 PTS patients were enrolled in the study. The mean age of these patients was 55.39 ± 11.81, including 19 male patients. Stent implantation was successful in 22 PTS patients, with a technical success rate of 70.97%. The average Villalta scores of the stent-implanted group and the non-stent-implanted group were 5.95 ± 2.57 and 5.78 ± 2.95, respectively, with no significant difference observed. In the stent-implanted group, the perioperative patency rate was 81.81% (18/22), and the follow-up patency rates were 68.18% (15/22) within 3 months, 59.09% (13/22) within 6 months, 45.45% (10/22) within 1 year, and 36.36% (8/22) within 2 years. Based on the stent placement segments, the 22 PTS patients were divided into two subgroups: the iliofemoral vein balloon dilation + iliofemoral vein stent implantation (FV-S) subgroup and the iliofemoral vein balloon dilation + iliac vein stent implantation (FV-B) subgroup. In the FV-S subgroup, the perioperative patency rate was 100.00% (14/14), and the follow-up patency rates were 85.71% (12/14), 71.43% (10/14), 57.14% (8/14) and 50.00% (7/14), which were higher than those for overall stent patency of all patients. The postoperative patency rates in the FV-B subgroup were 50.00% (4/8), 37.50% (3/8), 37.50% (3/8), 25.00% (2/8), and 12.50% (1/8). The secondary postoperative patency rates in the FV-B subgroup were 100.00% (8/8), 87.50% (7/8), 75.00% (6/8), 62.50% (5/8) and 50.00% (4/8). CONCLUSIONS: For PTS patients with iliofemoral vein occlusion but patent inflow, iliofemoral vein stent implantation is a more efficient therapeutic option than iliofemoral vein balloon dilation with iliac vein stent implantation for PTS patients.

MicroRNA profile of circulating CD4+ T cells in aged patients with atherosclerosis obliterans.

BACKGROUND: To evaluate the specificity of the expression patterns of microRNAs (miRNAs) in circulating CD4+ T cells in aged patients with atherosclerosis obliterans (ASO). METHODS: A comprehensive miRNA expression study was conducted using a miRNA microarray of CD4+ T cells isolated from peripheral blood mononuclear cells (PBMCs) of 33 patients with ASO and 24 healthy donors. A t test was used for statistical analysis, and the average linkage method was used for hierarchical clustering. The results were validated by qRT-PCR. Putative targeted pathways associated with validated miRNAs were predicted with the online software DIANA miRPath. RESULTS: We identified 44 miRNAs based on a cutoff value of a 1.3-fold change in expression between the two groups, with 18 miRNAs showing a false discovery rate (FDR) p value < 0.05. The qRT-PCR analysis validated differences in 12 miRNAs, and 6 miRNAs were proven to be differentially expressed among three age groups (age: 35-55 years; 56-75 years; 76-95 years): the miRNAs miR-21 (p: 0.0008; 0.0009; 0.0022), miR-29b (p: 0.453; < 0.0001; < 0.0001), and miR-374b (p: < 0.0001; < 0.0001; 0.2493) showed upregulated expression in patients with ASO, while miR-142-3p (p: < 0.0001; < 0.0001; < 0.0001), miR-142-5p (p: < 0.0001; < 0.0001; < 0.0001), and miR-150 (p: < 0.0001; < 0.0001; 0.0001) showed downregulated expression in patients with ASO. The validated miRNAs participated in CD4+ T cell activation, proliferation, and migration pathways. CONCLUSIONS: Circulating CD4+ T cells in aged patients with ASO may show a distinct molecular signature. This is the first time that a distinctive, validated miRNA profile from circulating CD4+ T cells in atherosclerosis has been presented. This miRNA signature may be used to help elucidate the underlying mechanism of atherosclerosis. Further clinical studies and in-depth reports will contribute to identifying predictive and therapeutic targets in these patients with atherosclerosis.

Integrative analysis prioritizes the relevant genes and risk factors for chronic venous disease.

OBJECTIVE: Chronic venous disease (CVD) refers to a range of symptoms resulting from long-term morphological and functional abnormalities of the venous system. However, the mechanism of CVD development remains largely unknown. Here, we aim to provide more information on CVD pathogenesis, prevention strategies, and therapy development through the integrative analysis of large-scale genetic data. METHODS: Genetic data were obtained from publicly accessible databases. We used different approaches, including Functional Mapping and Annotation, DEPICT, Sherlock, SMR/HEIDIS, DEPICT, and NetWAS to identify possible causal genes for CVD. Candidate genes were prioritized to further literature-based review. The differential expression of prioritized genes was validated by microarray from the Gene Expression Omnibus, a public genomics data repository and real-time quantitative polymerase chain reaction of varicose vein specimens. The causal relationships between risk factors and CVD were assessed using the two-sample Mendelian randomization approach. RESULTS: We identified 46 lead single-nucleotide polymorphisms and 26 plausible causal genes for CVD. Microarray data indicated differential expression of possible causal genes in CVD when compared with controls. The expression levels of WDR92, RSPO3, LIMA, ABCB10, DNAJC7, C1S, and CXCL1 were significantly downregulated (P < .05). PHLDA1 and SERPINE1 were significantly upregulated (P < .05). Dysregulated expression of WDR92, RSPO3, and CASZ1 was also found in varicose vein specimens by quantitative polymerase chain reaction. Two-sample Mendelian randomization suggested causative effects of body mass index (odds ratio [OR], 1.008; 95% confidence interval [CI], 1.005-1.010), standing height (OR, 1.009; 95% CI, 1.007-1.011), college degree (OR, 0.983; 95% CI, 0.991-0.976), insulin (OR, 0.858; 95% CI, 0.794-0.928), and metformin (OR, 0.944; 95% CI, 0.904-0.985) on CVD. CONCLUSIONS: Our study integrates genetic and gene expression data to make an effective risk gene prediction and etiological inferences for CVD. Prioritized candidate genes provide more insights into CVD pathogenesis, and the causative effects of risk factors on CVD that deserve further investigation.