Central nervous injury risk factors after endovascular repair of a thoracic aortic aneurysm with type B aortic dissection

Aortic dissection is the deadliest disease of the cardiovascular system.Type B aortic dissection accounts for 30%-60%of aortic dissections and is mainly treated by endovascular repair of thoracic endovascular aneurysm repair(TEVAR).However,patients are prone to various complications after surgery,with central nervous system injury being the most common,which seriously affects their prognosis and increases the risk of disability and death.Therefore,exploring the risk factors of central nervous system injury after TEVAR can provide a basis for its prevention and control.AIM To investigate the risk factors for central nervous system injury after the repair of a thoracic endovascular aneurysm with type B aortic dissection.METHODS We enrolled 306 patients with type B aortic dissection who underwent TEVAR at our hospital between December 2019 and October 2022.The patients were categorized into injury(n=159)and non-injury(n=147)groups based on central nervous system injury following surgery.The risk factors for central nervous system injury after TEVAR for type B aortic dissection were screened by comparing the two groups.Multivariate logistic regression analysis was performed.RESULTS The Association between age,history of hypertension,blood pH value,surgery,mechanical ventilation,intensive care unit stay,postoperative recovery times on the first day after surgery,and arterial partial pressure of oxygen on the first day after surgery differed substantially(P<0.05).Multivariate logistic regression analysis indicated that age,surgery time,history of hypertension,duration of mechanical ventilation,and intensive care unit stay were independent risk factors for central nervous system injury after TEVAR of type B aortic dissection(P<0.05).CONCLUSION For high-risk patients with central nervous system injury after TEVAR of type B aortic dissection,early intervention measures should be implemented to lower the risk of neurological discomfort following surgery in high-risk patients with central nervous system injury after TEVAR for type B aortic dissection.

A Case of Thoracic Aortic Aneurysm with Hemoptysis as the First Symptom

This article reports a case of thoracic aortic aneurysm with hemoptysis as the first clinical manifestation, hemoptysis as the first clinical manifestation is very uncommon and to the best of our knowledge, only twenty of such cases have been previously reported. The case report presented here constitutes the longest course of the disease reported in medical literature, and good recovery after thoracic endovascular aortic repair, may help us to increase the understanding and diagnosis of the disease.

Secondary aorto-esophageal fistula after thoracic aortic aneurysm endovascular repair treated by covered esophageal stenting

Thoracic endovascular aortic repair for thoracic aortic aneurysms is an accepted alternative to open surgery, especially in patients with significant comorbidities. The procedure itself has a low risk of complications and fistulas to surrounding organs are rarely reported. An 86-year-old patient was admitted to our hospital with gastro intestinal(GI) bleeding and a suspected aortoesophageal fistula. Eight months prior, the patient had undergone a stent graft repair of a mycotic thoracic aneurysm. Computerized tomography angiography and upper GI endoscopy confirmed an aortoesophageal fistula, which was treated by esophageal stenting. With early recognition, esophageal stenting may have a role in the initial emergency control of bleeding from and palliation of aortoesophageal fistula.

Study on hemodynamics in patient-specific thoracic aortic aneurysm

The objective of this study is to investigate the hemodynamics in patient-specific thoracic aortic aneurysm and discuss the reason for formation of aortic plaque.A 3-Dimensional pulsatile blood flow in thoracic aorta with a fusiform aneurysm and 3 main branched vessels was studied numerically with the average Reynolds number of 1399 and the Womersley number of 19.2.Based on the clinical 2-Dimensional CT slice data,the patient-specific geometry model was constructed using medical image process software.Unsteady,incompressible,3-Dimensional Navier-Stokes equations were employed to solve the flow field.The temporal distributions of hemodynamic variables during the cardiac cycle such as streamlines,wall shear stresses in the arteries and aneurysm were analyzed. Growth and rupture mechanisms of thoracic aortic aneurysm in the patient can be analyzed based on patient-specific model and hemodynamics simulation.

The incidence rate and histological characteristics of intimal hyperplasia in elastase-induced experimental abdominal aortic aneurysms in mice

Intimal hyperplasia(IH)is a negative vascular remodeling after arterial injury.IH occasionally occurs in elastase-induced abdominal aortic aneurysm(AAA)mouse models.This study aims to clarify the incidence and histological characteristics of IH in aneurysmal mice.A retrospective study was conducted by including 42 male elastaseinduced mouse AAA models.The IH incidence,aortic diameters with or without IH,and hyperplasia lesional features of mice were analyzed.Among 42 elastase-induced AAA mouse models,10 mice developed mild IH(24%)and severe IH was found in only 2 mice(5%).The outer diameters of the AAA segments in mice with and without IH did not show significant difference.Both mild and severe IH lesions show strong smooth muscle cell positive staining,but endothelial cells were occasionally observed in severe IH lesions.There was obvious macrophage infiltration in the IH lesions of the AAA mouse models,especially in mice with severe IH.However,only a lower numbers of T cells and B cells were found in the IH lesion.Local cell-secreted matrix metalloproteinases(MMP)2 was highly expressed in all IH lesions,but MMP9 was only overexpressed in severe lesions.In conclusion,this study is the first to demonstrate the occurrence of aneurysmal IH and its histological characteristics in an elastaseinduced mouse AAA model.This will help researchers better understand this model,and optimize it for use in AAA-related research.

Innovation in pathogenesis and management of aortic aneurysm

Aortic aneurysm(AA)refers to the persistent dilatation of the aorta,exceeding three centimeters.Investigating the pathophysiology of this condition is important for its prevention and management,given its responsibility for more than 25000 deaths in the United States.AAs are classified based on their location or morphology.various pathophysiologic pathways including inflammation,the immune system and atherosclerosis have been implicated in its development.Inflammatory markers such as transforming growth factorβ,interleukin-1β,tumor necrosis factor-α,matrix metalloproteinase-2 and many more may contribute to this phenomenon.Several genetic disorders such as Marfan syndrome,Ehler-Danlos syndrome and Loeys-Dietz syndrome have also been associated with this disease.Recent years has seen the investigation of novel management of AA,exploring the implication of different immune suppressors,the role of radiation in shrinkage and prevention,as well as minimally invasive and newly hypothesized surgical methods.In this narrative review,we aim to present the new contributing factors involved in pathophysiology of AA.We also highlighted the novel management methods that have demonstrated promising benefits in clinical outcomes of the AA.

Causal Relationship between Chronic Obstructive Pulmonary Disease and Abdominal Aortic Aneurysm: A Mendelian Randomization Study

Background: Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory lung condition associated with significant morbidity and mortality. Observational studies indicate a positive correlation between COPD and the risk of abdominal aortic aneurysm (AAA), suggesting individuals with COPD are more likely to develop AAA. However, the causal relationship between COPD and AAA remains unclear. Method: This study employed a bidirectional Mendelian Randomization (MR) approach to assess the causal relationship between COPD and AAA. A two-step MR analysis was conducted to evaluate the mediating effect of 1400 circulating metabolites between COPD and AAA. Expression quantitative trait loci (eQTL) were sourced from the MRC Integrative Epidemiology Unit (MRC-IEU) database, and MR analysis was performed using the TwoSampleMR R package. The results were filtered using the Inverse Variance Weighted (IVW) method to identify genes strongly associated with both COPD and AAA. Furthermore, the Super Exact Test R package was utilized to determine the overlapping genes between COPD and AAA. Enrichment analysis for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was conducted using the clusterProfiler R package. Protein-protein interaction (PPI) analysis was carried out using STRING v12.0. Results: The IVW method indicated a causal relationship between the risk increase of COPD and AAA (OR: 1.47, 95% CI: 1.16 - 1.86, p = 0.001). Among 1400 circulating metabolites, plasma-free proline was identified as mediating the relationship between COPD and AAA, with a mediation effect proportion of −4.6% (95% CI: −9.032%, −0.164%, p = 0.042). Additionally, PPI analysis revealed 20 functionally interrelated genes mediating the linkage between COPD and AAA. KEGG enrichment analysis showed functional enrichment of these genes in the pathway of aldosterone synthesis and secretion. Conclusion: Our study supports a causal relationship between COPD and an increased risk of AAA. Specifically, plasma-free proline and pathways related to aldosterone synthesis and secretion may play key roles in the connection between COPD and AAA.

Effects of COL1A1 and SYTL2 on inflammatory cell infiltration and poor extracellular matrix remodeling of the vascular wall in thoracic aortic aneurysm

Background:Thoracic aortic aneurysm(TAA)is a fatal cardiovascular disease,the pathogenesis of which has not yet been clarified.This study aimed to identify and validate the diagnostic markers of TAA to provide a strong theoretical basis for developing new methods to prevent and treat this disease.Methods:Gene expression profiles of the GSE9106,GSE26155,and GSE155468 datasets were acquired from the Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)were identified using the"limma"package in R.Least absolute shrinkage and selection operator(LASSO),support vector machine-recursive feature elimination(SVM-RFE),random forest,and binary logistic regression analyses were used to screen the diagnostic marker genes.Single-sample gene set enrichment analysis(ssGSEA)was used to estimate immune cell infiltration in TAA.Results:A total of 16 DEGs were identified.The enrichment and functional correlation analyses showed that DEGs were mainly associated with inflammatory response pathways and collagen-related diseases.Collagen type I alpha 1 chain(COL1A1)and synaptotagmin like 2(SYTL2)were identified as diagnostic marker genes with a high diagnostic value for TAA.The expression of COL1A1 and SYTL2 was considerably higher in TAA vascular wall tissues than in the corresponding normal tissues,and there were significant differences in the infiltration of immune cells between TAA and normal vascular wall tissues.Additionally,COL1A1 and SYTL2 expression were associated with the infiltration of immune cells in the vascular wall tissue.Single-cell analysis showed that COL1A1 in TAA was mainly derived from fibroblasts and SYTL2 mainly from cluster of differentiation(CD)8+T cells.In addition,single-cell analysis indicated that fibroblasts and CD8+T cells in TAA were significantly higher than those in normal arterial wall tissue.Conclusions:COL1A1 and SYTL2 may serve as diagnostic marker genes for TAA.The upregulation of SYTL2 and COL1A1 may be involved in the inflammatory infiltration of the vessel wall and poor extracellular matrix remodeling,promoting the progression of TAA.

Safety and Efficacy of Endovascular Aortic Repair for Abdominal Aortic Aneurysms with a Hostile Neck Anatomy

Objective This study aimed to investigate the safety and efficacy of endovascular aortic repair(EVAR)for the treatment of an abdominal aortic aneurysm(AAA)with a hostile neck anatomy(HNA).Methods From January 1,2015 to December 31,2019,a total of 259 patients diagnosed with an AAA who underwent EVAR were recruited into this study.Based on the morphological characteristics of the proximal neck anatomy,the patients were divided into the HNA group and the friendly neck anatomy(FNA)group.The patients were followed up for up to 4 years.Results The average follow-up time was 1056.1±535.5 days.Type I endoleak occurred in 4 patients in the HNA group,and 2 patients in the FNA group.Neither death nor intraoperative switch to open repair occurred in either group.The time of the operation was significantly longer in the HNA group(FNA vs.HNA,99.2±51.1 min vs.117.5±63.8 min,P=0.011).There were no significant differences in short-term clinical success rate(P=0.228)or midterm clinical success rate(P=0.889)between the two groups.The overall mortality rate was 10.4%,and Kaplan-Meier survival analysis indicated that the two groups had similar cumulative survival rates at the end of the follow-up period(P=0.889).Conclusion EVAR was feasible and safe in patients with an AAA with a proximal HNA.The early and midterm results were promising;however,further studies are needed to verify the long-term effectiveness of EVAR.

Relationship between acute kidney injury before thoracic endovascular aneurysm repair and in-hospital outcomes in patients with type B acute aortic dissection

Objective Acute kidney injury （AKI） frequently occurs after catheter-based interventional procedures and increases mortality. However, the implications of AKI before thoracic endovascular aneurysm repair （TEVAR） of type B acute aortic dissection （AAD） remain unclear. This study evaluated the incidence, predictors, and in-hospital outcomes of AKI before TEVAR in patients with type B AAD. Methods Between 2009 and 2013, 76 patients were retrospectively evaluated who received TEVAR for type B AAD within 36 h from symptom onset. The patients were classified into no-AKI vs. AKI groups, and the severity of AKI was further staged according to kidney disease： im- proving global outcomes criteria before TEVAR. Results The incidence of preoperative AKI was 36.8%. In-hospital complications was significantly higher in patients with preoperative AKI compared with no-AKI （50.0% vs. 4.2%, respectively; P 〈 0.001）, including acute renal failure （21.4% vs. O, respectively; P 〈 0.001）, and they increased with severity of AKI （P 〈 0.001）. The maximum levels of body tem- perature and white blood cell count were significantly related to maximum serum creatinine level before TEVAR. Multivariate analysis showed that systolic blood pressure on admission （OR： 1.023; 95% CI： 1.003-1.044; P ： 0.0238） and bilateral renal artery involvement （OR： 19.076; 95% CI： 1.914 190.164; P = 0.0120） were strong predictors of preoperative AKI. Conclusions Preoperative AKI frequently occurred in patients with type B AAD, and correlated with higher in-hospital complications and enhanced inflammatory reaction. Systolic blood pressure on admission and bilateral renal artery involvement were major risk factors for AKI before TEVAR.

Custom Made Fenestrated Stent Graft Collapse after Thoracic Endovascular Aortic Repair: A Case Report

We present a case of stent graft collapse after performing thoracic endovascular aortic repair with a custom-made fenestrated stent graft. The patient was a 70-year-old woman with an asymptomatic aneurysm of the distal aortic arch, and thoracic endovascular aortic repair was performed. The patient showed a blood pressure difference between the left arm and the right arm on postoperative day (POD) 17 prompting the performance of a chest computed tomography scan which revealed stent graft collapse. She then underwent staged debranching of thoracic endovascular aortic repair. Stent graft collapse is a rare but well-described complication of thoracic endovascular repair. Therefore, patients who undergo such a procedure should be carefully monitored for signs and symptoms, which suggest the possibility of stent collapse.

Effects of moxibustion at 46°C on blood lipids and related indicators of thoracic aortic endothelium in a hyperlipidemia rat model

Objective:To observe the effects of moxibustion at different temperatures(38℃,46℃)on blood lipids,endothelial morphology of the thoracic aorta,serum endothelin-1(ET-1),calcitonin gene-related peptide(CGRP),nitric oxide(NO),and endothelial NO synthase(eNOS)in hyperlipidemic rats.Methods:Using the random number table method,60 Sprague Dawley rats were randomly and evenly divided into blank,model,38℃-moxibustion,and 46℃-moxibustion groups.Rats in the 3 experimental groups were fed a high-fat feed to model hyperlipidemia in rats.Rats in the 38℃-moxibustion and 46℃-moxibustion groups were moxibustion on the Shenque and bilateral Zusanli acupoints for 10 minutes each,once every other day for 4 weeks,at temperatures of 38±1℃ and 46±1℃.After that,rat blood samples were collected to detect blood lipids and ET-1,CGRP,eNOS and NO.Take the endotheal tissue of the thoracic aorta to do HE staining.Results:(1)The serum total cholesterol,triglycerides,and low-density lipoprotein cholesterol of rats in the 46℃-moxibustion group were significantly lower than those in the model and 38℃-moxibustion groups.(2)Revealed by hematoxylin and eosin staining,showed necrosis in the local vascular endothelial cells and mild inflammatory cell infiltration in the tunica adventitia of the hyperlipidemic rats.These endothelial morphologies did not improve significantly after moxibustion at 38℃ but did improve at 46℃.(3)Compared with the blank group,serum ET-1 was significantly higher and serum CGRP,NO,eNOS were significantly lower in the model group.Compared with the model and the 38℃-moxibustion groups,serum ET-1 was significantly lower and serum CGRP,NO,eNOS were significantly higher in 46℃-moxibustion groups.Conclusion:Moxibustion at 46℃ effectively regulated blood lipids,improved the morphology of the vascular endothelium,and protected vascular endothelial function.

Extensive complex thoracoabdominal aortic aneurysm salvaged by surgical graft providing landing zone for endovascular graft:A case report

BACKGROUND Surgical repair of complex abdominal aortic aneurysm is associated with a higher perioperative mortality and morbidity.The advent of endovascular aortic repair(EVAR)has reduced perioperative complications,although the utilization of such techniques is limited by lesion characteristics,such as involvement of the visceral or renal arteries(RA)and/or presence of a sealing zone.CASE SUMMARY A 60-year-old male presented with a Crawford type IV complex thoracoabdominal aortic aneurysm(CAAA)starting directly distal to the diaphragm extending to both common iliac arteries(CIAs).The CAAA consist of a proximal and distal aneurysmal sac separated by a 1 cm-healthy zone in the infrarenal level.Due to the poor performance of the patient and the expansive disease,we planned a stepwise-combined surgery and EVAR to minimize invasiveness.A branched graft was implanted after surgical debranching of the visceral and RA.Since the patient had renal and liver injury after surgery,the second stage EVAR was performed 10 mo later.The stent graft was implanted from the distal portion of surgical branched graft to both CIAs during EVAR.The patient has been uneventful for 5-years after discharge and is being followed in the outpatient clinic.CONCLUSION The current case demonstrates that the surgical graft can provide a landing zone for second stage EVAR to avoid aggressive surgery in patients with poor performance with a long hostile CAAA.

Experimental and computational studies on the flow fields in aortic aneurysms associated with deployment of AAA stent-grafts

Pulsatile flow fields in rigid abdominal aortic aneurysm （AAA） models were investigated numerically, and the simulation results are found in good agreement with particle image velocimetry （PIV） measurements. There are one or more vortexes in the AAA bulge, and a fairly high wall shear stress exists at the distal end, and thus the AAA is in danger of rupture. Medical treatment consists of inserting a vascular stent-graft in the AAA, which would decrease the blood impact to the inner walls and reduce wall shear stress so that the rupture could be prevented. A new computational model, based on porous medium model, was developed and results are documented. Therapeutic effect of the stent-graft was verified numerically with the new model.

The Elevated Expression of Osteopontin and NF-κB in Human Aortic Aneurysms and Its Implication

The expression and significance of osteopontin （OPN） and NF-κB in patients with thoracic aortic aneurysm （TAA） and abdominal aortic aneurysm （AAA） were investigated. Thirteen TAA specimens, 20 AAA specimens and 6 normal aortic specimens were collected. The expression of OPN, nuclear factor-κB P65 （NF-κB P65）, urokinase plasminogen activator （uPA）, matrix metalloproteinase-2 （MMP-2） and matrix metalloproteinase-9 （MMP-9） were detected by using immunohisto-chemistry and Western blotting was employed to determine the expression of OPN and NF-κB P65. Immunohistochemical results showed that the expression of OPN, NF-κB P65, uPA, MMP-2 and MMP-9 was positive in all TAA and AAA specimens and negative in normal specimens, with the difference being statistically significant （P〈0.05）. There was no difference in the expression between TAA and AAA specimens （P〉0.05）. Correlation analysis revealed that there existed a positive correlation between the expression of OPN and that of NF-κB P65, uPA, MMP-2 and MMP-9 and between the expression of NF-κB P65 and that of uPA, MMP-2, MMP-9 （P〈0.05）. Western blotting demonstrated that OPN and NF-κB P65 were positive in AAA and TAA specimens, and negative in normal specimens with the differences being statistically significant （P〈0.05）. There were no statistically significant differences in the expression of OPN and NF-κB P65 between AAA and TAA specimens （P〉0.05）. It was concluded that OPN and NF-κB P65 were involved in the pathogenesis of TAA and AAA. OPN can up-regulate the expression of MMP and uPA via NF-κB signaling pathway thereby accelerating the degradation of extracellular matrix and playing an important role in the pathogenesis and development of TAA and AAA.

Incidental extravascular findings in computed tomographic angiography for planning or monitoring endovascular aortic aneurysm repair: Smoker patients, increased lung cancer prevalence?

AIM To validate the feasibility of high resolution computed tomography(HRCT) of the lung prior to computed tomography angiography(CTA) in assessing incidental thoracic findings during endovascular aortic aneurysm repair(EVAR) planning or follow-up.METHODS We conducted a retrospective study among 181 patients(143 men, mean age 71 years, range 50-94) referred to our centre for CTA EVAR planning or followup. HRCT and CTA were performed before or after 1 or 12 mo respectively to EVAR in all patients. All HRCT examinations were reviewed by two radiologists with 15 and 8 years experience in thoracic imaging. The results were compared with histology, bronchoscopy or follow-up HRCT in 12, 8 and 82 nodules respectively. RESULTS There were a total of 102 suspected nodules in 92 HRCT examinations, with a mean of 1.79 nodules per patient and an average diameter of 9.2 mm(range 4-56 mm). Eightynine out of 181 HRCTs resulted negative for the presence of suspected nodules with a mean smoking history of 10 pack-years(p-y, range 5-18 p-y). Eighty-two out of 102(76.4%) of the nodules met criteria for computed tomography follow-up, to exclude the malignant evolution. Of the remaining 20 nodules, 10 out of 20(50%) nodules, suspected for malignancy, underwent biopsy and then surgical intervention that confirmed the neoplastic nature: 4(20%) adenocarcinomas, 4(20%) squamous cell carcinomas, 1(5%) small cell lung cancer and 1(5%) breast cancer metastasis); 8 out of 20(40%) underwent bronchoscopy(8 pneumonia) and 2 out of 20(10%) underwent biopsy with the diagnosis of sarcoidosis.CONCLUSION HRCT in EVAR planning and follow-up allows to correctly identify patients requiring additional treatments, especially in case of lung cancer.

Abdominal aortic aneurysm： Treatment options, image visualizations and follow-up procedures

Abdominal aortic aneurysm is a common vascular disease that affects elderly population.Open surgical repair is regarded as the gold standard technique for treatment of abdominal aortic aneurysm,however,endovaseular aneurysm repair has rapidly expanded since its first introduction in 1990s.As a less invasive technique,endovascular aneurysm repair has been confirmed to be an effective alternative to open surgical repair,especially in patients with co-morbid conditions.Computed tomography （CT） angiography is currently the preferred imaging modality for both preoperative planning and post-operative follow-up.2D CT images are complemented by a number of 3D reconstructions which enhance the diagnostic applications of CT angiography in both planning and follow-up of endovascular repair.CT has the disadvantage of high cummulative radiation dose,of particular concern in younger patients,since patients require regular imaging follow-ups after endovascular repair,thus,exposing patients to repeated radiation exposure for life.There is a trend to change from CT to ultrasound surveillance of endovascular aneurysm repair.Medical image visualizations demonstrate excellent morphological assessment of aneurysm and stent-grafts,but fail to provide hemodynamic changes caused by the complex stent-graft device that is implanted into the aorta.This article reviews the treatment options of abdominal aortic aneurysm,various image visualization tools,and follow-up procedures with use of different modalities including both imaging and computational fluid dynamics methods.Future directions to improve treatment outcomes in the follow-up of endovascular aneurysm repair are outlined.

Transarterial Embolization versus Translumber Embolization for Type Ⅱ Endoleak after Endovascular Abdomi nal Aortic Aneurysm Repair:A Meta-Analysis

Objective Type II endoleak is the most common subtype of endoleak as a complication after endovascular aneurysm repair(EVAR).The efficacy of transarterial(TA)embolization and translumber(TL)embolization in the management of type II endoleak remains equipoise.The aim of this study is to compare the technical and clinical success between TA embolization andTL embolization for type II endoleak after EVAR.Methods The protocol was registered(CRD 42018114453)and the electronic databases(Pubmed,Embase,Web of Science,and Cochrane)were systematically searched till March 2019.The search terms included EVAR,type II endoleak,and embolization.The articles were read and extracted by two authors independently to include randomized control trails and retrospective studies that compared TA embolization and TL embolization in patients who developed type II endoleak after EVAR.The technical and clinical success rates were metaanalyzed with random effect model.Results A total of 6 articles with 268 patients and 290 type II endoleaks were included.The pooled odds ratio(OR)of technical success rate for TA vs.TL was 0.56(95%C7,0.10-3.18;P=0.51)and the pooled OR of clinical success rate for TA vs.TL was 0.31(95%CI,0.07-1.29;P=0.11).As a limitation,6 articles were all retrospective studies which may lead to bias.Conclusion Both TA.andTL could be eflective procedure of embolizations to resolve the type II endoleak.The metaanalysis result indicated that TA embolization was not inferior toTL embolization in technical success and clinical success.

Rapamycin Treatment Attenuates Angiotensin Ⅱ-induced Abdominal Aortic Aneurysm Formation via VSMC Phenotypic Modulation and Down-regulation of ERK1/2 Activity

The aim of the present study is to address the effect of rapamycin on abdominal aortic aneurysm（AAA） and the potential mechanisms. A clinically relevant AAA model was induced in apolipoprotein E-deficient（ApoE-/-） mice, in which miniosmotic pump was implanted subcutaneously to deliver angiotensin Ⅱ（Ang Ⅱ） for 14 days. Male ApoE-/-mice were randomly divided into 3 groups： saline infusion, Ang Ⅱ infusion, and Ang Ⅱ infusion plus intraperitoneal injection of rapamycin. The diameter of the supra-renal abdominal aorta was measured by ultrasonography at the end of the infusion. Then aortic tissue was excised and examined by Western blotting and histoimmunochemistry. Ang Ⅱ with or without rapamycin treatment was applied to the cultured vascular smooth muscle cells（VSMCs） in vitro. The results revealed that rapamycin treatment significantly attenuated the incidence of Ang Ⅱinduced-AAA in ApoE-/-mice. Histologic analysis showed that rapamycin treatment decreased disarray of elastin fibers and VSMCs hyperplasia in the medial layer. Immunochemistry staining and Western blotting documented the increased phospho-ERKl/2 and ERK1/2 expression in aortic walls in Ang Ⅱ induced-AAA,as well as in human lesions. Whereas in the rapamycintreated group, decreased phospho-ERK1/2 expression level was detected. Moreover, rapamycin reversed Ang Ⅱ-induced VSMCs phenotypic change both in vivo and in vitro. Based on those results, we confirmed that rapamycin therapy suppressed Ang Ⅱ-induced AAA formation in mice, partially via VSMCs phenotypic modulation and down-regulation of ERK1/2 activity.

Long Noncoding RNA Expression Signatures of Abdominal Aortic Aneurysm Revealed by Microarray

Objective This study is aimed at observing the role of long noncoding RNAs（lncR NAs） in the pathogenesis of abdominal aortic aneurysm（AAA）.Methods Lnc RNA and m RNA expression signatures of AAA tissues and normal abdominal aortic tissues（NT） were analyzed by microarray and further verified by Real-time quantitative reverse-transcription PCR（q RT-PCR）.The lnc RNAs-m RNAs targeting relationships were identified using computational analysis.The effect of lnc-ARG on 5-lipoxygenase（ALOX5） expression was tested in HeL a cells.Results Differential expressions of 3,688 lncR NAs and 3,007 m RNAs were identified between AAA and NT tissues.Moreover,1,284 differentially expressed long intergenic noncoding RNAs and 206 differentially expressed enhancer-like lnc RNAs adjacent to protein-coding genes were discerned by bioinformatics analysis.Some differentially expressed lncR NAs and m RNAs between AAA and normal tissue samples were further verified using q RT-PCR.A co-expression network of coding and noncoding genes was constructed based on the correlation analysis between the differentially expressed lnc RNAs and mR NAs.In addition,the lnc-ARG located within the upstream of ALOX5 was sorted as a noncoding transcript by analyzing the protein-coding potential using computational analysis.Furthermore,we found that lnc-ARG can decrease the m RNA level of ALOX5 and reactive oxygen species production in He La cells.Conclusion This study revealed new lnc RNA candidates are related to the pathogenesis of AAA.