Deciphering smooth muscle cell heterogeneity in atherosclerotic plaques and constructing model: a multi-omics approach with focus on KLF15/IGFBP4 axis.

BACKGROUND: Ruptured atherosclerotic plaques often precipitate severe ischemic events, such as stroke and myocardial infarction. Unraveling the intricate molecular mechanisms governing vascular smooth muscle cell (VSMC) behavior in plaque stabilization remains a formidable challenge. METHODS: In this study, we leveraged single-cell and transcriptomic datasets from atherosclerotic plaques retrieved from the gene expression omnibus (GEO) database. Employing a combination of single-cell population differential analysis, weighted gene co-expression network analysis (WGCNA), and transcriptome differential analysis techniques, we identified specific genes steering the transformation of VSMCs in atherosclerotic plaques. Diagnostic models were developed and validated through gene intersection, utilizing the least absolute shrinkage and selection operator (LASSO) and random forest (RF) methods. Nomograms for plaque assessment were constructed. Tissue localization and expression validation were performed on specimens from animal models, utilizing immunofluorescence co-localization, western blot, and reverse-transcription quantitative-polymerase chain reaction (RT-qPCR). Various online databases were harnessed to predict transcription factors (TFs) and their interacting compounds, with determination of the cell-specific localization of TF expression using single-cell data. RESULTS: Following rigorous quality control procedures, we obtained a total of 40,953 cells, with 6,261 representing VSMCs. The VSMC population was subsequently clustered into 5 distinct subpopulations. Analyzing inter-subpopulation cellular communication, we focused on the SMC2 and SMC5 subpopulations. Single-cell subpopulation and WGCNA analyses revealed significant module enrichments, notably in collagen-containing extracellular matrix and cell-substrate junctions. Insulin-like growth factor binding protein 4 (IGFBP4), apolipoprotein E (APOE), and cathepsin C (CTSC) were identified as potential diagnostic markers for early and advanced plaques. Notably, gene expression pattern analysis suggested that IGFBP4 might serve as a protective gene, a hypothesis validated through tissue localization and expression analysis. Finally, we predicted TFs capable of binding to IGFBP4, with Krüppel-like family 15 (KLF15) emerging as a prominent candidate showing relative specificity within smooth muscle cells. Predictions about compounds associated with affecting KLF15 expression were also made. CONCLUSION: Our study established a plaque diagnostic and assessment model and analyzed the molecular interaction mechanisms of smooth muscle cells within plaques. Further analysis revealed that the transcription factor KLF15 may regulate the biological behaviors of smooth muscle cells through the KLF15/IGFBP4 axis, thereby influencing the stability of advanced plaques via modulation of the PI3K-AKT signaling pathway. This could potentially serve as a target for plaque stability assessment and therapy, thus driving advancements in the management and treatment of atherosclerotic plaques.

Near-infrared responsive gold nanorods for highly sensitive colorimetric and photothermal lateral flow immuno-detection of SARS-CoV-2.

The highly infectious characteristics of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlight the necessity of sensitive and rapid nucleocapsid (N) protein-based antigen testing for early triage and epidemic management. In this study, a colorimetric and photothermal dual-mode lateral flow immunoassay (LFIA) platform for the rapid and sensitive detection of the SARS-CoV-2 N protein was developed based on gold nanorods (GNRs), which possessed tunable local surface plasma resonance (LSPR) absorption peaks from UV-visible to near-infrared (NIR). The LSPR peak was adjusted to match the NIR emission laser 808 nm by controlling the length-to-diameter ratio, which could maximize the photothermal conversion efficiency and achieve photothermal detection signal amplification. Qualitative detection of SARS-CoV-2 N protein was achieved by observing the strip color, and the limit of detection was 2 ng mL-1, while that for photothermal detection was 0.096 ng mL-1. Artificial saliva samples spiked with the N protein were analyzed with the recoveries ranging from 84.38% to 107.72%. The intra-assay and inter-assay coefficients of variation were 6.76% and 10.39%, respectively. We further evaluated the reliability of this platform by detecting 40 clinical samples collected from nasal swabs, and the results matched well with that of nucleic acid detection (87.5%). This method shows great promise in early disease diagnosis and screening.

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.

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.

The application of contrast-enhanced ultrasound for sentinel lymph node evaluation and mapping in breast cancer patients.

Background: To retrospectively investigate the application of contrast-enhanced ultrasound on sentinel lymph node (SLN-CEUS) for SLN evaluation and mapping in breast cancer patients. Methods: Patients diagnosed with breast cancer at the First Affiliated Hospital of Sun Yat-sen University from June 2019 to March 2021 were conveniently evaluated by SLN-CEUS. The results of SLN-CEUS and B mode-ultrasound (BUS) were collected and compared. For patients who only underwent SLN-CEUS, we conducted a 1:1 propensity score matching (PSM). The diagnostic parameters, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), false negative rate (FNR), false positive rate (FPR), and proportion of undetermined diagnoses were compared between the SLN-CEUS and BUS cohorts. The identification rate and FNR of sentinel lymph node biopsy (SLNB) were also assessed. Results: There were 327 patients in each of the SLN-CEUS and BUS cohorts. Among the entire cohort, both NPV [90.2% (95% CI, 85.4-93.5%) vs. 83.5% (95% CI, 77.8-88.0%), P=0.048] and accuracy [80.7% (95% CI, 76.5-85.0%) vs. 73.7% (95% CI, 68.9-78.5%), P<0.001] of SLN-CEUS were significantly higher than those of BUS. In non-neoadjuvant treatment (NAT) patients, the NPV [94.7% (95% CI, 89.9-97.4%) vs. 85.5% (95% CI, 79.1-90.2%), P=0.007] and accuracy [87.6% (95% CI, 83.2-92.0%) vs. 76.0% (95% CI, 70.4-81.5%), P<0.001] of SLN-CEUS were significantly higher than those of BUS. In NAT patients, no difference in diagnostic efficacy was found. The proportion of undetermined diagnoses of SLN-CEUS was significantly lower than that of BUS (5.8% vs. 15.3%, P<0.001). The identification rate of SLN-CEUS in overall patients, non-NAT patients, and NAT patients was 94.2%, 96.3%, and 89.9%, respectively. The FNR of SLNB with the blue-dye tracer in combination with SLN-CEUS in overall patients, non-NAT patients, and NAT patients was 7.3%, 4.0%, and 12.5%, respectively. Conclusions: Compared to BUS, SLN-CEUS is a better technique for diagnosing SLNs in early breast cancer patients, showing superiority in multiple diagnostic parameters. However, the diagnostic value of SLN-CEUS in NAT patients is still undetermined. SLN-CEUS is a promising mapping method in SLNB, with a high identification rate and a low FNR when used in combination with a blue-dye tracer.

The Efficacy of Low-Kilovoltage X-Rays Intraoperative Radiation as Boost for Breast Cancer: A Systematic Review and Meta-Analysis.

Background: Intraoperative radiotherapy (IORT) is a novel promising technology that may replace external beam radiation therapy (EBRT) as boost for patients receiving breast-conserving surgery. To better evaluate the efficacy of IORT using low-kilovoltage (low-kV) X-rays as boost, we presented this meta-analysis according to the PRISMA checklist. Methods: Studies reported survival outcomes of intraoperative radiation using low-kilovoltage X-rays system (Intrabeam®, Carl Zeiss Meditec, Dublin, CA, USA) as boost were identified through electronic bibliographic database: PUBMED. The meta-analysis module in Stata (16.0) is used to pool the studies. A Poisson regression model is used to predict a 5-year local recurrence rate. Results: Twelve studies including 3006 cases were included in the final analysis, with a median follow-up of 55 months weighted by sample size. The pooled local recurrence rate is 0.39% per person-year (95% CI: 0.15%-0.71%), with a low degree of heterogeneity (I2 = 0%). The predicted 5-year local recurrence rate was 3.45%. No difference in pooled local recurrence rate was found between non-neoadjuvant patients studies and neoadjuvant patients studies (0.41% per person-year vs. 0.58% per person-year, P = 0.580). Conclusions: This study shows that low-kV IORT is an effective method as boost in breast cancer patients, with a low pooled local recurrence rate and low predicted 5-year local recurrence rate. Besides, no difference in the local recurrence rate was found between non-neoadjuvant patients studies and neoadjuvant patients studies. Low-kV IORT boost may be a promising alternative to EBRT boost in the future, which is being tested in the ongoing TARGIT-B trial.

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.

Identification of necroptosis-related gene TRAF5 as potential target of diagnosing atherosclerosis and assessing its stability.

BACKGROUND: Atherosclerosis (AS) is a leading cause of morbidity and mortality in older patients and features progressive formation of plaques in vascular tissues. With the progression of atherosclerosis, plaque rupture may occur and cause stroke, myocardial infarction, etc. Different forms of cell death promote the formation of a necrotic core of the plaque, leading to rupture. Necroptosis is a type of programmed cell death that contributes to the development of cardiovascular disease. However, the role of necroptosis in AS has not yet been investigated. METHODS: The Gene Expression Omnibus (GEO) database was used to obtain gene expression profiles. Differentially expressed genes (DEGs) and necroptosis gene sets were used to identify necroptosis-related differentially expressed genes (NRDEGs). The NRDEGs were used to construct a diagnostic model and were further screened using least absolute shrinkage selection operator (LASSO) regression and random forest (RF) analysis. The discriminatory capacity of the NRDEGs was evaluated using receiver operating characteristic (ROC) curves. Immune infiltration levels were estimated based on CIBERSORTx analysis. The GSE21545 dataset, containing survival information, was used to determine prognosis-associated genes. Univariate and multivariate Cox regression analyses combined with survival analysis determined gene prognostic values. RNA and protein levels were detected by RT-qPCR and western blotting in arteriosclerosis obliterans(ASO) and normal vascular tissues. Vascular smooth muscle cells (VSMCs) were treated with oxidized low-density lipoprotein (ox-LDL) to develop cell models of advanced AS. The effects of protein knockdown on necroptosis were assessed by western blotting and flow cytometry. EdU and Cell Counting Kit-8 assays were used to examine cell proliferation. RESULTS: TNF Receptor Associated Factor 5 (TRAF5) was identified as a diagnostic marker for AS based on the AUC value in both the GSE20129 and GSE43292 datasets. According to differential expression analysis, LASSO regression analysis, RF analysis, univariate analysis, multivariate analysis, and gene-level survival analysis, TRAF5 was markedly associated with necroptosis in AS. Silencing TRAF5 promotes necroptosis and attenuates the proliferation of ox-LDL-induced cell models of advanced AS. CONCLUSIONS: This study identified a diagnostic marker of necroptosis-related atherosclerosis, TRAF5, which can also be used to diagnose and assess atherosclerotic plaque stability. This novel finding has important implications in the diagnosis and assessment of plaque stability in atherosclerosis.

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.

Retrospective Analysis of Carotid Body Tumor Surgical Management: Roles of Preoperative Image Investigation and Preoperative Embolization.

BACKGROUND: Carotid body tumors (CBT) surgery is a challenging procedure, and the role of embolization (EMB) in CBT surgery has remained unclear. This study is performed to analyze the management of CBTs, particularly the use of preoperative EMB and image features in minimizing surgical complications. METHODS: A total of 200 CBTs were identified among 184 medical records involving CBT surgery. Regression analysis was used to explore the prognostic predictors of cranial nerve deficit (CND), including image features. In addition, blood loss, operation times, and complication rates were compared between patients who had surgery only versus patients who had surgery along with preoperative EMB. RESULTS: Overall, 96 males and 88 females were identified for inclusion in the study, with a median age of 37.0 years. Computed tomography angiography (CTA) showed the presence of a tiny gap adjacent to the encasement of carotid vessels, which could help minimize carotid arterial injury. High-lying tumors that encased the cranial nerve were usually managed with synchronous cranial nerve resection. Regression analysis revealed that the incidence of CND was positively associated with Shamblin Ⅲ, high-lying, and a maximal CBT diameter of ≥ 5 cm. Among 146 EMB cases, 2 cases of intracranial arterial EMB occurred. No statistical difference was found between the EBM and non-EBM groups in terms of bleeding volume, operation time, blood loss, blood transfusion requirement, stroke, and permanent CND. Subgroup analysis revealed that EMB decreased CND in Shamblin III and low-lying tumors. CONCLUSIONS: CBT surgery should be performed with preoperative CTA to identify favorable factors for minimizing surgical complications. Shamblin Ⅲ or high-lying tumors, as well as CBT diameter, are predictors of permanent CND. EBM does not reduce blood loss or shorten operation time.

The feasibility of small-caliber veins for autogenous arteriovenous fistula creation: A single-center retrospective study.

Objective: Autogenous arteriovenous fistula (AVF) is recommended as the first choice for hemodialysis vascular access. A small-caliber vein is one of the independent risk factors for AVF maturation and patency. However, the specific threshold is still unclear, making it difficult to accurately determine whether these vessels are suitable for AVF creation. Design: This is a single-center retrospective study. Method: Patients who underwent AVF creation in our medical center between January 2020 and September 2022 and satisfied the eligibility criteria were included in this retrospective study. Logistic regression analysis was performed to identify risk factors for functional maturation and additional intervention. The optimal cutoff value was determined based on the receiver operating curve (ROC) and the Youden index. Kaplan-Meier analysis was utilized in further patency rate comparisons. Result: A total of 125 forearm AVFs were created in 121 patients with end-stage renal disease (ESRD). The mean age was 53.88 ± 15.10 years. Preoperative vascular Doppler ultrasound (DUS) was conducted and recorded in 106 cases (84.80%). The mean targeted artery and vein diameters were 2.17 ± 0.54 and 1.71 ± 0.75 mm, respectively. Small-caliber vein is the risk factor for functional maturation failure (OR = 0.256, 95%CI [0.06-0.75], p = 0.033) and additional intervention (OR = 0.306, 95% CI [0.09-0.78], p = 0.031). The optimal cutoff value is 1.35 mm (augmented) when specificity and sensitivity reach 80 and 63.7%, respectively. The AVFs with a vein diameter of more than 1.35 mm (augmented) showed higher patency rates (p < 0.01). Conclusion: After comprehensive DUS evaluation, intraoperative hydrodilation, postoperative active exercise and intensive DUS detection, and application of balloon-assisted maturation, if necessary, using a vein more than 1.35 mm (augmented), could achieve satisfactory functional maturation and postoperative patency in AVF formation.

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.

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.

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.

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.

The Long Non-coding RNA AC148477.2 Is a Novel Therapeutic Target Associated With Vascular Smooth Muscle Cells Proliferation of Femoral Atherosclerosis.

Arteriosclerosis obliterans (ASO) is a limb manifestation of large vessel atherosclerosis. Phenotype switching of vascular smooth muscle cells (VSMCs) occurs in the course of the pathological process. The underlying mechanism of SMCs proliferation remains unclear. Several studies have demonstrated that the dysregulation of long non-coding RNA (lncRNAs) plays a pivotal part in the progression of ASO by exacerbating the proliferation of VSMCs. Based on the endogenous competitive RNA (ceRNA) hypothesis, the mechanism of lncRNAs involved in the pathology of VSMCs was exposed, while the entire map of the regulatory network remains to be elucidated. In the current study, genes and the lncRNAs modules that are relevant to the clinical trait were confirmed through weighted gene co-expression network analysis (WGCNA). In this study, we comprehensively constructed a specific lncRNAs-mediated ceRNA and RBP network. The three lncRNAs, HMGA1P4, C5orf66, and AC148477.2, influenced the proliferation of VSMCs and were found to be associated with the immune landscape, thus they were ultimately screened out. Further verification revealed that AC147488.2 was significantly down-regulated in both ASO arteries and all stages of proliferative VSMCs, which implied that AC147488.2 might have a significant impact on ASO. This finding would improve our understanding of the epigenetic regulation of ASO and unravel novel diagnostic and therapeutic targets.

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.

Circular RNA circGSE1 promotes angiogenesis in ageing mice by targeting the miR-323-5p/NRP1 axis.

Age is an important factor in many cardiovascular diseases, in which endothelial cells (ECs) play an important role. Circular RNAs (circRNAs) have been reported in many cardiovascular diseases, but their role in ageing EC-related angiogenesis is unclear. We aimed to identify a functional circRNA that regulates angiogenesis during ageing and explore its specific mechanism. In this study, we searched for differentially expressed circRNAs in old endothelial cells (OECs) and young endothelial cells (YECs) by circRNA sequencing and found that circGSE1 was significantly downregulated in OECs. Our study showed that circGSE1 could promote the proliferation, migration and tube formation of OECs in vitro. In a mouse model of femoral artery ligation and ischemia, circGSE1 promoted blood flow recovery and angiogenesis in the ischemic limbs of ageing mice. Mechanistically, we found that overexpressing circGSE1 reduced miR-323-5p expression, increased neuropilin-1 (NRP1) expression, and promoted proliferation, migration, and tube formation in OECs, while knocking down circGSE1 increased miR-323-5p expression, reduced NRP1 expression, and inhibited proliferation, migration, and tube formation in YECs. During EC ageing, circGSE1 may act through the miR-323-5p/NRP1 axis and promote endothelial angiogenesis in mice. Finally, the circGSE1/miR-323-5p/NRP1 axis could serve as a potential and promising therapeutic target for angiogenesis during ageing.

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.