Dataset Information

NEAT1 promotes the repair of abdominal aortic aneurysms of endothelial progenitor cells via regulating miR-204-5p/Ang-1.

ABSTRACT:

Purpose

To clarify the regulatory effect of Nuclear-enriched abundant transcript 1 (NEAT1) on abdominal aortic aneurysm (AAA) model rats and isolated endothelial progenitor cells (EPCs).

Methods

The AAA rat model was established by CaCl₂ stimulation, and overexpressed NEAT1 was injected into rats through tail vein. Abdominal aorta lesions and numbers of EPCs in tissues and peripheral blood were examined by hematoxylin-eosin, immunofluorescence and flow cytometry. The extracted EPCs were identified by microscopy, DiI-ac-LDL staining and flow cytometry. Effect of overexpressed/silencing NEAT1 on the viability, migration, tube formation and VEGF content of EPCs was investigated by MTT-, wound-healing, tube formation assays and ELISA, respectively. The expressions of NEAT1, miR-204-5p, Angiopoietin-1 (Ang-1)/ERK pathway were determined by qRT-PCR and Western blot as needed. The targeting relationships between NEAT1 and miR-204-5p, and miR-204-5p and Ang-1 were predicted on starBase, TargetScan and confirmed by dual-luciferase experiments. The mutual regulation effect was studied through rescue experiments.

Results

Overexpressed NEAT1 not only reduced inflammatory infiltration and increased the number of EPCs in abdominal aorta and peripheral blood, but also promoted the viability, migration, tube formation of EPCs, increased VEGF content and upregulated the expression of the Ang-1/ERK pathway in EPCs. However, silencing NEAT1 produced opposite results. NEAT1 targeting miR-204-5p inhibited the functional effects of miR-204-5p on of EPCs. Overexpressed/silencing Ang-1 partially reversed the effects of NEAT1 or miR-204-5p on the characteristics of EPCs.

Conclusion

NEAT1 competitively binds with miR-204-5p and up-regulates Ang-1 expression in EPCs to effectively improve the proliferation, migration and angiogenesis of EPCs.

SUBMITTER: Shi C

PROVIDER: S-EPMC8129351 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:PurposeThe PEVAR Trial demonstrated that compared to open femoral exposure, elective percutaneous endovascular AAA repair (ePEVAR) is associated with decreased perioperative morbidity and access site complications. We hypothesized that PEVAR for ruptured AAA (rPEVAR) may also improve perioperative morbidity compared to open femoral exposure (rEVAR). There are currently no reports that evaluate the utility and outcomes of rPEVAR.Materials and methodsFrom 2015 to 2021, all patients who underwent an endovascular repair of a ruptured AAA at a single institution were included in the study and grouped into rPEVAR and rEVAR. Demographics, procedural details (successful preclose technique, conversion to femoral cutdown), postoperative variables (blood transfusion, ICU and hospital length of stay) and short-term outcomes (30-day major adverse events (30-day MAE) and 30-day femoral access-site complications (30-day FAAC)) were collected and compared with 50 historical ePEVAR patients from the PEVAR Trial. Statistical significance was determined using χ 2 or Fisher's exact test for categorical variables, and Mann-Whitney U-test for continuous variables.Results35 patients were identified (21 rPEVAR; 14 rEVAR), 86% were male with a mean age of 72 ± 9 years. All patients underwent emergent endovascular aortic repair with 100% technical success. Seventeen patients (49%) presented with evidence of hemorrhagic shock and 22 patients (63%) had blood transfusion. 30-day MAE occurred in 12 patients (34%) (7 rPEVAR; 5 rEVAR). There was no difference in demographic, perioperative outcomes and 30-day MAE rate between rPEVAR and rEVAR patients. Compared to ePEVAR patient (from PEVAR trial), rPEVAR patients had higher rate of 30-day MAE (34% vs. 6%; p < 0.006) but no difference in 30-day FAAC (19% vs. 12%; p = 0.54). The success rate of the preclose technique was higher in ePEVAR compared to rPEVAR (96% vs. 76%; p = 0.02), but the rate of conversion to femoral cutdown was similar between the two groups (10% vs. 4%; p = 0.57).ConclusionEmergent rPEVAR appears to have similar outcomes when compared to rEVAR. Although patients undergoing rPEVAR have higher 30-day major adverse events rate compared to ePEVAR, the method of percutaneous femoral cannulation does not appear to increase the overall procedural or 30-day femoral artery access-site complications.

Project description:Importance:Knowledge regarding the long-term outcomes of elective treatment of abdominal aortic aneurysm (AAA) using endovascular aortic repair (EVAR) is increasing. However, data with greater than 10 years' follow-up remain sparse and are lacking from population-based studies. Objective:To determine the long-term outcomes of EVAR compared with open surgical repair (OSR) for elective treatment of AAA. Design, Setting, and Participants:This retrospective, population-based cohort study used linked administrative health data from Ontario, Canada, to identify all patients 40 years and older who underwent elective EVAR or OSR for AAA repair from April 1, 2003, to March 31, 2016, with follow-up terminating on March 31, 2017. A total of 17 683 patients were identified using validated procedure and billing codes and were propensity score matched. Analysis was conducted from June 26, 2018, to January 16, 2019. Exposures:Elective EVAR or OSR for AAA. Main Outcomes and Measures:The primary outcome was overall survival. Secondary outcomes were major adverse cardiovascular event-free survival, defined as being free of death, myocardial infarction, or stroke; reintervention; and secondary rupture. Results:Among 17 683 patients who received elective AAA repairs (mean [SD] age, 72.6 [7.8] years; 14 286 [80.8%] men), 6100 (34.5%) underwent EVAR and 11 583 (65.5%) underwent OSR. From these patients, 4010 well-balanced propensity score-matched pairs of patients were defined, with a mean (SD) age of 73.0 (7.6) years and 6583 (82.1%) men. In the matched cohort, the mean (SD) follow-up was 4.4 (2.7) years, and maximum follow-up was 13.8 years. The overall median survival was 8.9 years. Compared with OSR, EVAR was associated with a higher survival rate up to 1 year after repair (91.0% [95% CI, 90.1%-91.9%] vs 94.0% [95% CI, 93.3%-94.7%]) and a higher major adverse cardiovascular event-free survival rate up to 4 years after repair (69.9% [95% CI, 68.3%-71.3%] vs 72.9% [95% CI, 71.4%-74.4%]). Cumulative incidence of reintervention was higher among patients who underwent EVAR compared with those who underwent OSR at the 7-year follow-up (45.9% [95% CI, 44.1%-47.8%] vs 42.2% [95% CI, 40.4%-44.0%]). Survival analyses demonstrated no statistically significant differences in long-term survival, reintervention, and secondary rupture for patients who underwent EVAR compared with those who underwent OSR. Kaplan-Meier analysis suggested superior long-term major adverse cardiovascular event-free survival among patients who underwent EVAR compared with those who underwent OSR (32.6% [95% CI, 26.9%-38.4%] vs 14.1% [95% CI, 4.0%-30.4%]; stratified log-rank P < .001) during a maximum follow-up of 13.8 years. Conclusions and Relevance:Endovascular aortic repair was not associated with a difference in long-term survival during more than 13 years' maximum follow-up. The reasons for these findings will require studies to consider specific graft makes and models, adherence to instructions for use, and types and reasons for reintervention.

Project description:ObjectiveMortality after open repair for emergent complex abdominal aortic aneurysm (AAA) is poorly defined. This study evaluated the 30-day mortality of open complex AAA repair performed for rupture or other emergent indication using a national surgical registry. We subsequently identified factors associated with mortality.MethodsThe targeted vascular module from the American College of Surgeons National Surgical Quality Improvement Program was queried to identify patients undergoing open repair for juxtarenal and suprarenal AAAs or type IV thoracoabdominal aneurysms (TAAAs) for rupture or other emergent indication from 2011 to 2017. Univariate analyses were performed using the Fisher's exact test for categorical variables and the Wilcoxon rank sum test for continuous variables. Multivariable logistic regression was performed to identify factors independently associated with mortality.ResultsWe included 374 patients who underwent an emergent complex open AAA repair during the study period. There were 142 (38%) cases performed for rupture with hypotension, 141 (38%) for rupture without hypotension, 40 (11%) for symptomatic AAA, and 51 (14%) for another indication. The distribution by aneurysm type was 224 juxtarenal AAAs, 122 suprarenal AAAs, and 28 type IV TAAAs. Overall, there was a 30-day mortality of 32% (118 deaths). For those with juxtarenal AAA repair, 67 (30%) patients died within 30 days; there were 38 (31%) deaths within 30 days in those with suprarenal AAA, and 13 (46%) deaths within 30 days in those with type IV TAAA. On univariate analysis, preoperative variables associated with death were increasing age, use of a transperitoneal surgical approach, lower preoperative estimated glomerular filtration rate, low baseline albumin concentration (<3.5 g/dL), need for preoperative transfusion, low body mass index (<18.5 kg/m2), and hypotension at presentation. Intraoperative variables associated with mortality were supraceliac clamp location and concurrent renal revascularization. On multivariable analysis, factors independently associated with death included rupture with associated hypotension (reference: other emergent indication; adjusted odds ratio [AOR], 3.28; confidence interval [CI], 1.75-5.41; P < .001), age >60 years (reference: <60 years; AOR, 1.59; CI, 1.18-2.13; P = .002), longitudinal laparotomy incision (reference: retroperitoneal; AOR, 3.28; CI, 1.75-6.16; P < .001), and supraceliac cross-clamp (reference: clamp above one renal artery; AOR, 2.14; CI, 1.31-3.50; P = .003).ConclusionsNearly one-third of patients die within 30 days of emergent open complex AAA repair. Mortality is particularly high for patients with type IV TAAAs, approaching 50%. Predictors of 30-day mortality include rupture with associated hypotension, increasing age, supraceliac clamp location, and longitudinal transperitoneal repair approach. These results will help inform surgical decisions preoperatively and intraoperatively.