Protein Tyrosine Phosphatase SHP2 in Macrophages Acts as an Antiatherosclerotic Regulator in Mice.

BACKGROUND: Macrophages have versatile roles in atherosclerosis. SHP2 (Src homology 2 containing protein tyrosine phosphatase 2) has been demonstrated to play a critical role in regulating macrophage activation. However, the mechanism of SHP2 regulation of macrophage function in an atherosclerotic microenvironment remains unknown. METHODS: APOE (apolipoprotein E) or LDLR (low-density lipoprotein receptor) null mice treated with SHP099 were fed a Western diet for 8 weeks, while Shp2MKO:ApoE-/- or Shp2MKO:Ldlr-/- mice and exo-AAV8-SHP2E76K/ApoE-/- mice were fed a Western diet for 12 weeks. In vitro, levels of proinflammatory factors and phagocytic function were then studied in mouse peritoneal macrophages. RNA sequencing was used to identify PPARγ (peroxisome proliferative activated receptor γ) as the key downstream molecule. A PPARγ agonist was used to rescue the phenotypes observed in SHP2-deleted mice. RESULTS: Pharmacological inhibition and selective deletion in macrophages of SHP2 aggravated atherosclerosis in APOE and LDLR null mice with increased plaque macrophages and apoptotic cells. In vitro, SHP2 deficiency in APOE and LDLR null macrophages enhanced proinflammatory polarization and its efferocytosis was dramatically impaired. Conversely, the expression of gain-of-function mutation of SHP2 in mouse macrophages reduced atherosclerosis. The SHP2 agonist lovastatin repressesed macrophage inflammatory activation and enhanced efferocytosis. Mechanistically, RNA sequencing analysis identified PPARγ as a key downstream transcription factor. PPARγ was decreased in macrophages upon SHP2 deletion and inhibition. Importantly, PPARγ agonist decreased atherosclerosis in SHP2 knockout mice, restored efferocytotic defects, and reduced inflammatory activation in SHP2 deleted macrophages. PPARγ was decreased by the ubiquitin-mediated degradation upon SHP2 inhibition or deletion. Finally, we found that SHP2 was downregulated in atherosclerotic vessels. CONCLUSIONS: Overall, SHP2 in macrophages was found to act as an antiatherosclerotic regulator by stabilizing PPARγ in APOE/LDLR null mice.

Glucagon-like peptide-1 receptor agonist exendin 4 ameliorates diabetes-associated vascular calcification by regulating mitophagy through the AMPK signaling pathway.

BACKGROUND: Vascular calcification (VC) is a complication in diabetes mellitus (DM) patients. Osteogenic phenotype switching of vascular smooth muscle cells (VSMCs) plays a critical role in diabetes-related VC. Mitophagy can inhibit phenotype switching in VSMCs. This study aimed to investigate the role of the glucagon-like peptide-1 receptor (GLP-1R) agonist exendin 4 (EX4) in mitophagy-induced phenotype switching. MATERIALS AND METHODS: The status of VC in T2DM mice was monitored using Von Kossa and Alizarin Red S (ARS) staining in mouse aortic tissue. Human aortic smooth muscle cells were cultured in high glucose (HG) and ß-glycerophosphate (ß-GP) conditioned medium. Accumulation of LC3B and p62 was detected in the mitochondrial fraction. The effect of EX4 in vitro and in vivo was investigated by knocking down AMPKα1. RESULTS: In diabetic VC mice, EX4 decreased the percentage of von Kossa/ARS positive area. EX4 inhibited osteogenic differentiation of HG/ß-GP-induced VSMCs. In HG/ß-GP-induced VSMCs, the number of mitophagosomes was increased, whereas the addition of EX4 restored mitochondrial function, increased the number of mitophagosome-lysosome fusions, and reduced p62 in mitochondrial frictions. EX4 increased the phosphorylation of AMPKα (Thr172) and ULK1 (Ser555) in HG/ß-GP-induced VSMCs. After knockdown of AMPKα1, ULK1 could not be activated by EX4. The accumulation of LC3B and p62 could not be reduced after AMPKα1 knockdown. Knockdown of AMPKα1 negated the therapeutic effects of EX4 on VC of diabetic mice. CONCLUSION: EX4 could promote mitophagy by activating the AMPK signaling pathway, attenuate insufficient mitophagy, and thus inhibit the osteogenic phenotype switching of VSMCs.

The Impact of Balloon Pre-dilatation Techniques on Drug-Coated Balloon Therapy for Femoropopliteal Artery Disease: Six-Month Results From the CIVILIAN Registry.

OBJECTIVE: The purpose of this study is to compare the initial outcomes of using the Chocolate balloon pre-dilatation (CLP) and sequential enlarging angioplasty pre-dilatation (sequential balloon pre-dilation [SP]) techniques versus the conventional balloon pre-dilatation (CP) method prior to drug-coated balloon (DCB) treatment for femoropopliteal (FP) lesions. METHODS: This was a retrospective analysis of prospectively collected data from the CIVILIAN (Clinical InVestigation of different lesIon preparation modaLIty followed by DCB in femoropopliteal Artery occlusioN disease) registry. Between March 2021 and November 2022, 3 pre-dilation techniques used prior to the DCB angioplasty were included. The study endpoint included intraoperative finial severe dissection after provisional stent placement, bailout stenting rate, the diameter of the largest pre-dilation balloon and DCB, as well as major adverse events (MAEs), including death, major limb amputation, or target vessel revascularization at 6 months. RESULTS: During the study period, 435 limbs (429 patients) were pre-dilated before DCB treatment in FP lesions, 166 limbs were pre-dilated with Chocolate balloons, 93 limbs with sequential enlarging balloon pre-dilation technique, and 176 limbs with CP. The largest pre-dilation balloon was significantly larger in CLP and SP groups than that in the CP group (CLP 4.74±0.52 mm vs CP 4.36±0.64 mm, p<0.001; SP 4.82±0.69 mm vs CP 4.36±0.63 mm, p<0.001). A consistent result was shown in DCB diameter (CLP 4.86±0.44 mm vs CP 4.71±0.51 mm, p=0.003; SP 4.90±0.58 mm vs CP 4.71±0.51 mm, p=0.006). The bailout stenting rate was significantly lower in the CLP group than that in the CP group (18.1% vs 30.1%, p=0.011). The rates of MAEs at 6 months in the CLP and SP groups were comparable to those in the CP group (7.2% and 8.6% vs 6.3%, p>0.05). The risk for intraoperative bailout stenting rate was related to TASC D classification (3.59, 95% CI: 1.83-7.05, p<0.001), chronic total occlusion (CTO) lesion (1.82, 95% CI: 1.07-3.10, p=0.028), as well as pre-dilated with the conventional balloon (1.64, 95% CI: 1.00-2.69, p=0.048). CONCLUSIONS: By utilizing chocolate balloon and sequential enlarging angioplasty, it becomes possible to use larger pre-dilation balloons and DCBs. In addition, the use of the chocolate balloon can significantly reduce the need for bailout stenting when compared with conventional balloons. CLINICAL IMPACT: The utilization of a chocolate balloon and sequential enlarging angioplasty has emerged as a promising technique for angioplasty procedures. This approach allows for the use of larger pre-dilation balloons and drug-coated balloons. The use of the chocolate balloon can significantly reduce the need for bail-out stenting when compared to conventional balloons. Further research is required to determine the impact of vessel preparation techniques on the primary patency.

CDKN2B-AS1 mediates proliferation and migration of vascular smooth muscle cells induced by insulin.

Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the intimal hyperplasia in type 2 diabetes mellitus (T2DM) patients after percutaneous coronary intervention. We aimed to investigate the role of lncRNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) in VSMC proliferation and migration, as well as the underlying mechanism. T2DM model mice with carotid balloon injury were used in vivo and mouse aortic vascular smooth muscle cells (MOVAS) stimulated by insulin were used in vitro to assess the role of CDKN2B-AS1 in VSMC proliferation and migration following vascular injury in T2DM state. To investigate cell viability and migration, MTT assay and Transwell assay were conducted. To elucidate the underlying molecular mechanisms, the methylation-specific polymerase chain reaction, RNA immunoprecipitation, RNA-pull down, co-immunoprecipitation, and chromatin immunoprecipitation were performed. In vivo, CDKN2B-AS1 was up-regulated in common carotid artery tissues. In vitro, insulin treatment increased CDKN2B-AS1 level, enhanced MOVAS cell proliferation and migration, while the promoting effect was reversed by CDKN2B-AS1 knockdown. CDKN2B-AS1 forms a complex with enhancer of zeste homolog 2 (EZH2) and DNA methyltransferase (cytosine-5) 1 (DNMT1) to regulate smooth muscle 22 alpha (SM22α) methylation levels. In insulin-stimulated cells, SM22α knockdown abrogated the inhibitory effect of CDKN2B-AS1 knockdown on cell viability and migration. Injection of lentivirus-sh-CDKN2B-AS1 relieved intimal hyperplasia in T2DM mice with carotid balloon injury. Up-regulation of CDKN2B-AS1 induced by insulin promotes cell proliferation and migration by targeting SM22α through forming a complex with EZH2 and DNMT1, thereby aggravating the intimal hyperplasia after vascular injury in T2DM.

A systematic review and meta-analysis of primary bypass surgery compared with bypass surgery after endovascular treatment in peripheral artery disease patients.

OBJECTIVE: Both bypass surgery and endovascular treatment are well-recognized interventions for the treatment of peripheral artery disease; however, the effect of failed endovascular treatment on subsequent surgeries remains controversial. A systematic review was conducted to compare the outcomes of primary bypass and bypass surgery after endovascular treatment. METHODS: Three academic databases (Embase, PubMed, and Scopus) were searched from their inception to August 2022. Two independent investigators searched for studies that reported the outcomes of primary bypass surgery and bypass surgery after endovascular treatment in patients with peripheral artery disease. Abstracts and full-text studies were screened independently using duplicate data abstraction. Dichotomous outcome measures were reported using a random-effects model to generate a summary odds ratio (OR) and 95% confidence interval (CI). The risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: Seventeen retrospective observational studies were selected from 3911 articles and included 8064 patients, 6252 of whom underwent primary bypass surgery and 1812 underwent bypass surgery after endovascular treatment. The mean age was 69.0 years and 61.2% (n = 4938) were male. For perioperative outcomes, the 30-day results showed no difference in mortality (OR, 0.76; 95% CI, 0.53-1.10), or amputation (OR, 0.89; 95% CI, 0.67-1.20). For short- to mid-term outcomes, primary patency did not differ at 6 months (OR, 0.98; 95% CI, 0.81-1.19), 1 year (OR, 1.12; 95% CI, 0.97-1.30), or 2 years (OR, 1.17; 95% CI, 0.85-1.61) follow-up. Amputation-free survival did not differ at 6 months (OR, 1.03; 95% CI, 0.82-1.30), 1 year (OR, 1.09; 95% CI, 0.89-1.32), 2 years (OR, 1.18; 95% CI, 0.93-1.50), or 3 years (OR, 1.09; 95% CI, 0.84-1.40) of follow-up. No significant difference was found in overall survival or second patency. CONCLUSIONS: This meta-analysis of retrospective, nonrandomized, observational studies suggests that prior endovascular treatment of lower extremity arterial disease does not result in worse perioperative, short-term, or mid-term clinical outcomes of subsequent infrainguinal bypass surgery compared with patients without prior endovascular treatment.

A CT-based predictive model for stent-induced vessel damage: application to type B aortic dissection.

OBJECTIVES: The distal stent-induced new entry (distal SINE) is a life-threatening device-related complication after thoracic endovascular aortic repair (TEVAR). However, risk factors for distal SINE are not fully determined, and prediction models are lacking. This study aimed to establish a predictive model for distal SINE based on the preoperative dataset. METHODS: Two hundred and six patients with Stanford type B aortic dissection (TBAD) that experienced TEVAR were involved in this study. Among them, thirty patients developed distal SINE. Pre-TEVAR morphological parameters were measured based on the CT-reconstructed configurations. Virtual post-TEVAR morphological and mechanical parameters were computed via the virtual stenting algorithm (VSA). Two predictive models (PM-1 and PM-2) were developed and presented as nomograms to help risk evaluation of distal SINE. The performance of the proposed predictive models was evaluated and internal validation was conducted. RESULTS: Machine-selected variables for PM-1 included key pre-TEVAR parameters, and those for PM-2 included key virtual post-TEVAR parameters. Both models showed good calibration in both development and validation subsamples, while PM-2 outperformed PM-1. The discrimination of PM-2 was better than PM-1 in the development subsample, with an optimism-corrected area under the curve (AUC) of 0.95 and 0.77, respectively. Application of PM-2 in the validation subsample presented good discrimination with an AUC of 0.9727. The decision curve demonstrated that PM-2 was clinically useful. CONCLUSION: This study proposed a predictive model for distal SINE incorporating the CT-based VSA. This predictive model could efficiently predict the risk of distal SINE and thus might contribute to personalized intervention planning. CLINICAL RELEVANCE STATEMENT: This study established a predictive model to evaluate the risk of distal SINE based on the pre-stenting CT dataset and planned device information. With an accurate VSA tool, the predictive model could help to improve the safety of the endovascular repair procedure. KEY POINTS: • Clinically useful prediction models for distal stent-induced new entry are still lacking, and the safety of the stent implantation is hard to guarantee. • Our proposed predictive tool based on a virtual stenting algorithm supports different stenting planning rehearsals and real-time risk evaluation, guiding clinicians to optimize the presurgical plan when necessary. • The established prediction model provides accurate risk evaluation for vessel damage, improving the safety of the intervention procedure.

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

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

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

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

Drug-Coated Balloon Angioplasty of Infrapopliteal Lesions in Chronic Limb-Threatening Ischemia: Six-month Outcomes of PRIME-WIFI.

PURPOSE: To evaluate 6-month outcomes of drug-coated balloon (DCB) angioplasty of infrapopliteal lesions in patients with chronic limb-threatening ischemia (CLTI). METHODS: We analyzed 6-month follow-up data from the 10-center PRIME-WIFI prospective registry on 300 consecutive patients (33.000% female) with CLTI who underwent DCB angioplasty for infrapopliteal arterial lesions. The primary outcome was freedom from major adverse event (MAE), a composite of major amputation, all-cause death, and clinically-driven target limb reintervention (CD-TLR). Secondary outcomes included amputation-free survival (AFS), freedom from each primary outcome component, primary sustained clinical improvement, and quality of life (QOL) score. Independent risk factors of MAE were determined using Cox proportional hazards regression analysis. RESULTS: A total of 409 infrapopliteal lesions in 312 limbs were treated with DCB, with 54.167% of the limbs being treated for isolated infrapopliteal lesions. By Kaplan-Meier analysis, at 6 months post- procedure (follow-up rate, 85.000%), freedom from MAE was 86.353%; AFS was 90.318%; and freedom from major amputation, all-cause death, and CD-TLR were 96.429%, 93.480%, and 95.079%, respectively. At 6-month follow-up, 83.590% of patients showed primary sustained clinical improvement, and QOL score (4.902±1.388) improved compared with that before procedure (2.327±1.109; p<0.001). Chronic renal insufficiency, chronic obstructive pulmonary disease, Rutherford grade, and postoperative infrapopliteal runoff score were independent risk factors for MAE within 6 months. CONCLUSION: In CLTI, DCB angioplasty of infrapopliteal lesions yields acceptable early efficacy and safety. CLINICAL IMPACT: This study evaluated the 6-month outcomes of DCB angioplasty in infrapopliteal lesions in CLTI patients by analyzing multicenter prospective data, showing that infrapopliteal DCB angioplasty can be performed with acceptable freedom from MAE rate, amputation-free survival rate, freedom from major amputation rate, survival rate, and freedom from CD-TLR rate. No patient experienced DCB-related intraoperative distal embolism. Chronic renal insufficiency, chronic obstructive pulmonary disease, Rutherford grade and postoperative infrapopliteal runoff score were independent risk factors for MAE within 6 months. Comparative real-world studies are needed.

Effects of Long Term Fatigue Cycling on In Situ Fenestrations of Polyethylene Terephthalate and Expanded Polytetrafluorethylene Thoracic Aortic Stent grafts: An Experimental Study.

OBJECTIVE: In this study, the long term durability of fenestrations after in situ fenestration (ISF) of five commercial thoracic aortic stent grafts was evaluated in an in vitro experiment after a simulated 10 year period. METHODS: Five different thoracic aortic stent grafts (Relay, Valiant, Hercules, TAG, and Ankura, with a diameter of 34 mm) received both needle and laser ISF in vitro. A Viabahn (11 × 50 mm) was released in each fenestration as a bridging stent graft. Long term fatigue tests (simulating 10 years) of each of the fenestrated stent grafts were then conducted in a flow fatigue test system. The area, shape, margin, and the long and short axis of all the fenestrations were evaluated with light microscopy before and after the fatigue test. The leakage from the fenestration junction before and after the long term fatigue was also measured. RESULTS: The experimental results showed no obvious difference between needle and laser fenestrations. The long axes of all the fenestrations remained unchanged, while the short axes increased after the fatigue test, which was significant in Relay, Valiant, and Hercules polyethylene terephthalate stent grafts. The shape scores of fenestrations improved after the fatigue test in Valiant and Hercules, remained unchanged in Relay and Ankura, and worsened in the TAG. After the fatigue cycling, the average leakage from the fenestration junction decreased in all the stent grafts, and the Ankura had the maximum decline rate. CONCLUSION: The ISF technique was durable over a simulated 10 year period. The fenestrations were positively remodelled to be more circular, and the leakage from the junction decreased after long term fatigue testing.

CircRNA-SCAF8 promotes vascular endothelial cell pyroptosis by regulating the miR-93-5p/TXNIP axis. / 环状RNA-SCAF8通过miR-93-5p/TXNIPé€šè·¯ä¿ƒè¿›è¡€ç®¡å† çš®ç»†èƒžç„¦äº¡.

OBJECTIVES: To investigate the role and mechanism of circRNA-SR-related CTD associated factor 8 (SCAF8) in regulating endothelial cell pyroptosis in high glucose environment. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured and divided into six groups. The normal control group and high glucose control group were cultured in cell culture medium with 5 and 33 mmol/L glucose, respectively. The RNA control group, circRNA-SCAF8 inhibition group, miR-93-5p overexpression group and miR-93-5p inhibition group were added with non-functional siRNA, circRNA-SCAF8 inhibitor, miR-93-5p overexpression molecule and miR-93-5p inhibitor in high glucose environment, respectively. Cell viability and pyroptosis were detected by cell counting kit-8 (CCK-8) assay, flow cytometry and Hoechst 33342/propidium iodide fluorescence double staining. Western blotting and enzyme-linked immunosorbent assay were used to detect the expression of pyroptosis-related factors including apoptosis-associated speck-like protein containing a CARD (ASC), cysteine aspartic acid specific protease-1 (caspase-1) and Gasdermin D (GSDMD), NOD like receptor protein 3 (NLRP-3), thioredoxin interacting proteins (TXNIP), IL-18 and IL-1ß. The expression of circRNA-SCAF8, miR-93-5p and TXNIP was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Fluorescence in situ hybridization (FISH) was used to locate circRNA-SCAF8 and miR-93-5p. Dual luciferase assay was used to verify the targeted regulatory relationship between miR-93-5p and upstream and downstream molecules. RESULTS: Compared with the RNA control group, the cell survival rate of circRNA-SCAF8 inhibition group and miR-93-5p overexpression group increased (both P<0.01), the pyroptosis decreased (both P<0.01), and the expressions of pyroptosis-related factors such as TXNIP, NLRP-3, caspase-1, GSDMD, ASC, IL-18 and IL-1ß were significantly decreased (all P<0.05). The expression of miR-93-5p was significantly increased after inhibition of circRNA-SCAF8 (P<0.01), and the expression of circRNA-SCAF8 tended to decrease after overexpression of miR-93-5p, but with no statistical significance (P>0.05). Dual luciferase assay showed that miR-93-5p downre-gulated circRNA-SCAF8 expression by binding to the 3 ´ UTR region of circRNA-SCAF8, and miR-93-5p downregulated TXNIP expression by binding to the 3 ´ UTR region of TXNIP. FISH showed that circRNA-SCAF8 and miR-93-5p were both located in the cytoplasm and were highly associated in the cells. qRT-PCR showed that the relative expression of TXNIP increased or decreased after overexpression or inhibition of miR-93-5p compared with the RNA control group, respectively (both P<0.05), suggesting that miR-93-5p could regulate TXNIP gene expression. CONCLUSIONS: CircRNA-SCAF8/miR-93-5p/TXNIP axis is involved in the regulation of pyroptosis in HUVECs under high glucose.

M6A methylation-mediated elevation of SM22α inhibits the proliferation and migration of vascular smooth muscle cells and ameliorates intimal hyperplasia in type 2 diabetes mellitus.

Abnormal proliferation of vascular smooth muscle cells (VSMCs) induced by insulin resistance facilitates intimal hyperplasia of type 2 diabetes mellitus (T2DM) and N6-methyladenosine (m6A) methylation modification mediates the VSMC proliferation. This study aimed to reveal the m6A methylation modification regulatory mechanism. In this study, m6A demethylase FTO was elevated in insulin-treated VSMCs and T2DM mice with intimal injury. Functionally, FTO knockdown elevated m6A methylation level and further restrained VSMC proliferation and migration induced by insulin. Mechanistically, FTO knockdown elevated Smooth muscle 22 alpha (SM22α) expression and m6A-binding protein IGF2BP2 enhanced SM22α mRNA stability by recognizing and binding to m6A methylation modified mRNA. In vivo studies confirmed that the elevated m6A modification level of SM22α mRNA mitigated intimal hyperplasia in T2DM mice. Conclusively, m6A methylation-mediated elevation of SM22α restrained VSMC proliferation and migration and ameliorated intimal hyperplasia in T2DM.

Optical trapping of multiple particles based on a rotationally-symmetric power-exponent-phase vortex beam.

In this paper, the optical trapping of multiple particles based on a rotationally-symmetric power-exponent-phase vortex beam (RSPEPVB) was introduced and demonstrated. Based on the theories of tight focusing and optical force, the optical force model of RSPEPVB was established to analyze the optical trapping force of tightly focused RSPEPVB. Then, an experimental setup of optical tweezer, by utilizing the RSPEPVB, was built to demonstrate that the optical tweezer of RSPEPVBs can achieve the optical trapping of multiple particles, and the number of captured particles is equal to the topological charge l of RSPEPVB, which shows that the RSPEPVBs can achieve multi-particles trapping with controllable number. Moreover, compared to vortex beam, the captured particles by RSPEPVB will not rotate around the circular light intensity distribution. The results will provide a new option for optical trapping of multiple particles in biomedicine, laser cooling and so on.

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

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

Covered Stents for Treatment of Visceral Artery Aneurysms: A Multicenter Study.

PURPOSE: To evaluate the safety and efficacy of covered stents for treatment of visceral artery aneurysms (VAA). METHODS: This multicenter retrospective study included patients with VAAs who were treated with covered stents between January 2015 and December 2020. A total of 65 patients (mean age, 58 years; range, 27-89 years) with 70 VAAs (60 true aneurysms [86%], 10 pseudoaneurysms [14%]) were included. Of the 65, 48 patients (74%) were asymptomatic. Patient demographics, endovascular treatments, and follow-up results were analyzed. RESULTS: All patients received covered stents. The mean diameter was 2.9 cm (range, 1.0-7.6 cm) for symptomatic aneurysms and 2.5 cm (range, 1.0-9.0 cm) for asymptomatic aneurysms. Of the asymptomatic aneurysms, 89% had a saccular shape. The mean distance between the ostium of the artery in which the aneurysm occurred and the aneurysm was 3.9 cm (median, 3.0 cm; range, 0.5-10 cm). Additional coil embolization was used in 7 aneurysms (10%). During the procedure, 68 (97%) aneurysms were completely excluded, while 2 (3%) had a Type Ib endoleak. After a mean follow-up of 20 months (range, 1-75 months), all patients were asymptomatic. Four endoleaks were recorded and left for close observation. Four stents (7%) had mild restenosis, while the rest of the stents were patent. CONCLUSIONS: Placement of covered stents in patients with VAAs excluded aneurysms and maintained artery patency.

Endovascular therapy versus medical treatment for spontaneous isolated dissection of the superior mesenteric artery.

BACKGROUND: Spontaneous isolated dissection of the superior mesenteric artery (SIDSMA) occurs when a tear in the inner layer of the superior mesenteric artery (SMA) allows blood to flow between the layers of the SMA, forcing the layers apart, and creating two lumens. Abdominal pain is the most prevalent clinical manifestation. Other people may have no symptoms or experience nausea, vomiting, diarrhea, or blood in their stools. For people with SIDSMA who are not suspected of intestinal necrosis or intra-abdominal bleeding, medical treatment and endovascular therapy are the main treatment options. There is no consensus on the optimum first-line management strategy. OBJECTIVES: To evaluate the benefits and harms of endovascular therapy versus medical treatment for spontaneous isolated dissection of the superior mesenteric artery (SIDSMA). SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 3 August 2021. SELECTION CRITERIA: We planned to include all randomized controlled trials (RCTs) which compared endovascular therapy and medical treatments for SIDSMA. We planned to exclude studies where participants were treated with open surgery. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were endovascular intervention rate and recurrent abdominal pain. Our secondary outcomes were open surgery rate, remodeling rate of SMA, new aneurysm formation of SMA, SMA occlusion, new dissection of SMA, death, symptom relief rate and complications of endovascular therapy. We planned to use GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We did not identify any RCTs to include in any analysis. AUTHORS' CONCLUSIONS: We were not able to include any RCTs that compared endovascular therapy versus medical treatment in people with SIDSMA. High-quality RCTs that evaluate the benefits and harms of these interventions are needed to help determine the optimal strategy for managing SIDSMA.

Endovascular Treatments for Coarctation of the Aorta with Concurrent Poststenotic Aneurysms in Adults.

BACKGROUND: Coarctation of the aorta with poststenotic aneurysms is rare and complex. Here we report a relatively large group of endovascular treatments for the disease. MATERIALS AND METHODS: Fifteen patients from two centers between 2006 and 2019 were included in the study. The patients were retrospectively divided into two groups. Patients in the complex group had insufficient proximal landing zone (<2 cm) or the zigzag shape of aorta. Their demographics, clinical manifestations, endovascular procedures, and follow-up results were analyzed. RESULTS: There were 7 patients in the simple group and 8 patients in the complex group. Eleven patients were symptomatic. Despite the unfavorable anatomy in the complex group, technical success reached 100%. The diameter of coarctation increased from 8.6 mm to 16.7 mm with poststenotic aneurysms successfully excluded at the same time. In patients without sufficient proximal landing zone, left subclavian artery was covered by the stent grafts and then sacrificed (three patients) or revascularized (four patients). Other than one patient who suffered iliac artery rupture and received open repair, there was no other perioperative complications. Computed tomography angiography repeated at mean 42 months postoperation confirmed patency of stents and the exclusion of aneurysms with no aortic wall injury. Mild endoleaks occurred in two patients in the complex group and were left to observation. During 55.0 months follow-up, except for one patient who received secondary left subclavian artery fenestration, all other patients remained asymptomatic. CONCLUSIONS: Endovascular treatments for coarctation of the aorta with poststenotic aneurysm showed a high technical success and could be an alternative solution for such disease.

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

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

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

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

Therapeutic method for early-stage second primary non-small lung cancer: analysis of a population-based database.

BACKGROUND: Early-stage non-small lung cancer patients may survive long enough to develop second primary lung cancers. However, few studies have accurately described the therapeutic method, evaluation or prognostic factors for long-term survival in this complex clinical scenario. METHODS: Patients who had first and second primary non-small lung cancer in the Surveillance, Epidemiology, and End Results database between 2004 and 2015 were evaluated. Patients were included when their tumors were pathologically diagnosed as non-small lung cancer and in the early-stage (less than 3 cm and with no lymph node metastasis). Therapeutic methods were categorized as lobectomy, sublobectomy or no surgery. The influence of different therapeutic methods on the overall survival rate was compared. RESULTS: For the first primary tumor, patients who underwent lobectomy achieved superior survival benefits compared with patients who underwent sublobectomy. For the second primary tumor, long-term survival was similar in patients who underwent lobectomy and those who underwent sublobectomy treatment. The multivariate analysis indicated that age, disease-free time interval, sex, and first and second types of surgery were independent prognostic factors for long-term survival. Our results showed that the 5-year overall survival rate was 91.9% when the disease-free interval exceeded 24 months. CONCLUSION: Lobectomy for the first primary tumor followed by sublobectomy for the second primary tumor may be a beneficial therapeutic method for patients. If the disease-free interval exceeds 24 months, the second primary tumor will have no influence on the natural course for patients diagnosed with a first primary non-small lung cancer.