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.

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.

Management of multiple type II endoleaks detected by duplex ultrasound after endovascular abdominal aneurysm repair

We reported a case of multiple type II endoleaks detected by duplex ultrasound after endovascular abdominal aneurysm repair. The patient was undergoing warfarin therapy. Duplex ultrasound was applied as the sole surveillance method during follow-up and provided the concerned information for reintervention. The endoleaks were successfully repaired by coil embolization of the collaterals from the internal lilac artery feeding the fourth lumbar artery.

Progression and Regression of Abdominal Aortic Aneurysms in Mice

Objective:Abdominal aortic aneurysm(AAA)is a significant medical problem with a high mortality rate.Nevertheless,the underlying mechanism for the progression and regression of AAA is unknown.Methods:Experimental model of AAA was first created by porcine pancreatic elastase incubation around the infrarenal aorta of C57BL/6 mice.Then,AAA progression and regression were evaluated based on the diameter and volume of AAA.The aortas were harvested for hematoxylin-eosin staining(HE),orcein staining,sirius red staining,immunofluorescence analysis and peris’prussian blue staining at the indicated time point.Finally,P-aminopropionitrile monofumarate(BAPN)was used to explore the underlying mechanism of the regression of AAA.Results:When we extended the observation period to 100 days,we not only observed an increase in the AAA diameter and volume in the early stage,but also a decrease in the late stage.Consistent with AAA diameter and volume,the aortic thickness showed the same tendency based on HE staining.The elastin and collagen content first degraded and then regenerated,which corresponds to the early deterioration and late regression of AAA.Then,endogenous up-regulation of lysyl oxidase(LOX)was detected,accompanying the regression of AAA,as detected by an immunofluorescent assay.BAPN and LOX inhibitor considerably inhibited the regression of AAA,paralleling the degradation of elastin lamella and collagen.Conclusion:Taken together,we tentatively conclude that endogenous re-generation of LOX played an influential role in the regression of AAA.Therefore,regulatory factors on the generation of LOX exhibit promising therapeutic potential against AAA.

High-risk factors related to the occurrence and development of abdominal aortic aneurysm

Abdominal aortic aneurysm(AAA) is a common and potentially dangerous vascular disease with many risk factors related to its occurrence and development. This review collects the results from recent studies of different comorbidities including hypertension, diabetes, and hyperlipidemia and summarizes their connections with AAA development and its underlying mechanisms. We believe that hypertension, diabetes, and hyperlipidemia can affect AAA occurrence and development, but more studies are needed to further explore the mechanisms.

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.

Identify Can didate Genes in the Interactio n betwee n Abdominal Aortic Aneurysm and Type 2 Diabetes Mellitus by Using Biomedical Discovery Support System

Objective To explore the candidate genes that play significant roles in the interconnection between abdominal aortic aneurysm(AAA)and type 2 diabetes mellitus(DM).Methods We used the Biomedical Discovery Support System(BITOLA)to screen out the candidate intermediate molecular(CIM)"Gene or Gene Product”that are related to AAA and DM.The dataset of GSE13760,GSE7084,GSE57691,GSE47472 were used to analyze the differentially expressed genes(DEGs)of AAA and DM compared to the healthy status.We used the online tool ofVenny 2.1 assisted by manual checking to identify the overlapped DEGs with the CIMs.The Human eFP Browser was applied to examine the tissue specific expression levels of the detected genes in order to recognize strong expressed genes in both human artery and pancreatic tissue.Results There were 86 CIMs suggested by the closed BITOLA system.Among all the DEGs of AAA and DM,8 genes in GSE7084(ISG20,ITGAX,DSTN,CCL5,CCR5,AGTR1,CD19,CD44)and 2 genes in GSE 13760(PSMD12,FAS)were found to be overlapped with the 86 CIMs.By manual checking and comparing with tissuespecific gene data through Human eFP Browser,the gene PSMD12(proteasome 26S subunit,non-ATPase 12)was recognized to be strongly expressed in both the aorta and pancreatic tissue.Conclusion We proposed a hypothesis through text mining that PSMD12 might be involved or potentially involved in the interconnection between AAA and DM,which may provide a new clue for studies on novel therapeutic strategies for the two diseases.

Supraceliac Aortic Clamping for Repair of Ruptured Abdominal Aortic Aneurysm in Patients with Short Aortic Neck Length

Objective: Prompt bleeding control with proximal aortic clamping and subsequent aortic repair are very important for ruptured abdominal aortic aneurysm. However, unsuitable anatomy, such as short aortic neck length, not only disturbs the means to an expeditious repair, but may also increase morbidity and mortality. In the present study, we aimed to evaluate the efficacy of supraceliac aortic clamping for improving surgical outcomes for patients with ruptured abdominal aortic aneurysm, who have a short aortic neck length. Method: Between April 2010 and September 2015, eighteen patients underwent emergent open surgical repair of ruptured abdominal aortic aneurysm. Eight patients with a short aortic neck length underwent supraceliac aortic clamping, and 10 underwent infrarenal aortic clamping. Results: The mean supraceliac aortic clamping time was 30 ± 7 minutes. There was 1 operative death in the infrarenal aortic clamping group due to respiratory failure, and the overall operative mortality was 6%. There were no significant differences between the 2 groups with respect to postoperative complication rates or mortality. Furthermore, there were no significant differences in variables of renal function between the 2 groups, through-out the study period. Conclusion: Supraceliac aortic clamping was associated with minimal mortality and morbidity, but not with harmful effects on postoperative renal function. Thus, supraceliac aortic clamping can be safely applied for ruptured abdominal aortic aneurysm with short aortic neck length.

Pheochromocytoma with abdominal aortic aneurysm presenting as recurrent dyspnea,hemoptysis,and hypotension:A case report

BACKGROUND Pheochromocytomas are rare endocrine tumors with various clinical manifestations,and few of them might present with profound,life-threatening conditions.CASE SUMMARY We report the case of a 65-year-old man who complained of sudden dyspnea and hemoptysis for half a day.There was no obvious cause for the patient to have dyspnea,coughing,or coughing up to approximately 100 mL of fresh blood.Finally,he was diagnosed with pheochromocytoma crisis(PCC),coexisting with an abdominal aortic aneurysm(AAA).CONCLUSION We report a case of pheochromocytoma presenting with recurrent hemoptysis,dyspnea and hypotension coexisting with an AAA.It not only proved the uncommon manifestations of pheochromocytoma but also directed clinicians to consider PCC among the possible diagnoses when meeting similar cases.Moreover,surgical excision is the most beneficial method for the treatment of pheochromocytoma coexisting with AAA when the situation is stable.

Kunming mouse strain is less susceptible to elastase-induced abdominal aortic aneurysms

Background:Porcine pancreatic elastase(PPE)is successfully used to induce abdominal aortic aneurysm(AAA)in mice.However,differences between mouse strains in susceptibility to PPE induction have been reported.Kunming mouse is one of the most frequently used strains in China but whether it is suitable for induction of AAA by PPE application remains unclear.Methods:PPE infusion(1.5 units/ml)in temporary controlled aorta was performed to induce AAAs in both C57BL/6J and Kunming mice.Phosphatebuffered saline(PBS)application was used as vehicle control.The aorta diameters of all mice were measured at days 0 and 14 after surgery to evaluate the AAA formation.Results:After 14 days of PPE or PBS infusion,all mice were sacrificed and aorta tissues were collected for histological staining analysis.At the 14th day after infusion,PPE successfully induced aortic dilation in Kunming mice and typical AAA in C57BL/6J mice.The aorta diameter increased by 0.23 mm in Kunming mice after PPE infusion,while it was 0.72 mm in the C57BL/6J strain.PPE induced mild elastin degradation,smooth muscle cell(SMC)depletion and mural leucocyte infiltration in Kunming mice,but in PPE-sensitive C57BL/6J mice,it induced total loss of SMCs,elastin disappearance and diffused infiltrated leucocytes in aortic aneurysmal segments.The effects of PPE in inducing angiogenesis and upregulating matrix metalloproteinase 2 and 9 expression in Kunming mice were also weaker than that in C57BL/6J mice.Conclusion:At the reported dose of PPE,Kunming mouse is not as susceptible to AAA formation as C57BL/6J mice.The failure of PPE to induce AAA formation in Kunming mice may be associated to its inability to boost a strong inflammatory response.

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.

Comparison of Clinical Effects of Abdominal Aortic Aneurysm Treatment with Open and Endovascular Techniques

Objective:To compare the therapeutic effects of endovascular and open surgery on abdominal aortic aneurysms.Methods:From June 2019 to May 2020,60 cases of abdominal aortic aneurysms(AAA)were divided into observation group(30 cases in endovascular technique group)and control group(30 cases in open technique group).Results:The blood loss,operative time and blood transfusion of the observation group were significantly lower than those of the control group(P<0.05).The incidence of postoperative complications is low,and the incidence of longterm complications is relatively high.Conclusion:In the treatment of abdominal aortic aneurysm,endovascular technology has the advantages of low risk,less trauma,and quick recovery after surgery.Open surgery is suitable for patients who cannot receive endovascular treatment.In order to achieve good treatment effects,it is necessary to choose an appropriate treatment method according to the actual situation of the patient.

Endovascular Repair of Abdominal Aortic Aneurysm May Not Provide Long-Term Survival Benefit

Purpose: To investigate the long term survival benefit for the treatment of abdominal aortic aneurysmal (AAA) disease with Endovascular Aneurysm Repair (EVAR). Our hypothesis is that patients undergoing EVAR have an equivalent survival to an age matched population. Methods: Between 1997 and 2014 all patients treated for an AAA with EVAR by a single surgeon were prospectively followed and at 12 monthly intervals ultrasonography was utilised to assess the size of the aorta after treatment. Data from the Births, Deaths and Marriages was also collected regarding the survival of these patients. As of 2003 all patients with AAA were treated electively with EVAR. Results: There were a total of 145 patients treated with EVAR for AAA during the study period, 143 who survived the 30-day post-operative period. The long-term survival following EVAR at one year was 95% (95% C.I.: 88% to 97%), at 5 years 56% (95% C.I.: 42% to 64%), and at 10 years 28% (95% C.I.: 17% to 42%). Compared to an age-matched population the EVAR group had a lower than expected long term survival (P < 0.0001). Discussion: EVAR for the treatment of abdominal aortic aneurysms can be achieved with acceptable 30 day survival and freedom from aneurysm related death. However selection of patients for EVAR may significantly effect long-term survival if patients are fit for EVAR but not open operation. The question arises as to whether EVAR should be performed in patients with questionable long-term survival, even if they are fit for this procedure.

Application Effects of Total Percutaneous Technique in Endovascular Repair of Abdominal Aortic Aneurysm

Objective:To investigate the effectiveness of total percutaneous technique in endovascular repair of abdominal aortic aneurysm.Methods:Divide patients into two groups based on random tests.The control group received conventional treatment,and the experimental group received modified treatment.The changes in self-management ability,comfort level and recovery time before and after treatment were compared between the two groups.Results:The comfort level and self-management ability of the experimental group were significantly higher than that of the control group,and the recovery time was significantly shorter than that of the control group.The difference was statistically significant(P<0.05).Conclusion:Puncture suture can safely and effectively repair the intracavity of abdominal aortic aneurysm.

Preoperative echocardiographic predictors for 1-year mortality in patients treated with standard endovascular aneurysm repair for abdominal aortic aneurysm

Background: Abdominal aortic aneurysm (AAA) and cardiovascular disease are intimately associated, the latter representing the most common cause of death in Sweden. Cardiac complications are held responsible for the majority of perioperative morbidity and mortality in patients undergoing repair of AAA. The importance of preoperative thorough cardiac assessment is therefore obvious. The aim of this study was to evaluate the prognostic significance of preoperative echocardiographic findings for 1-year mortality after elective endovascular aneurysm repair (EVAR) of infrarenal AAA. Design: Retrospective analysis. Methods: The 505 patients were identified in a prospective database for endovascular interventions between 1998 and 2011, and data were retrieved from patient records. Preoperative echocardiography reports in 380 patients were reviewed and findings were notified according to a predefined protocol. Results: The 1-year mortality rate was 6.7%. Severe valve disease was present in 8.7% of the patients, aortic valve stenosis being the leading cause of valve pathology. Severe valve disease (OR 3.5, 95% CI [1.2 - 10.7];p = 0.025) and chronic kidney disease grade ≥ 3 (OR 7.5, 95% CI [2.1 - 26.1];p = 0.002) were the only independent risk factors for increased mortality rate at 1-year. Conclusion: Echocardiography should be a part of the preoperative workup in AAA patients. Finding of severe valve disease should be further evaluated by a cardiologist prior to EVAR.

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.

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.

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.

MicroRNA–disease Network Analysis Repurposes Methotrexate for the Treatment of Abdominal Aortic Aneurysm in Mice

Abdominal aortic aneurysm(AAA)is a permanent dilatation of the abdominal aorta and is highly lethal.The main purpose of the current study is to search for noninvasive medical therapies for AAA,for which there is currently no effective drug therapy.Network medicine represents a cuttingedge technology,as analysis and modeling of disease networks can provide critical clues regarding the etiology of specific diseases and therapeutics that may be effective.Here,we proposed a novel algorithm to quantify disease relations based on a large accumulated microRNA–disease association dataset and then built a disease network covering 15 disease classes and 304 diseases.Analysis revealed some patterns for these diseases.For instance,diseases tended to be clustered and coherent in the network.Surprisingly,we found that AAA showed the strongest similarity with rheumatoid arthritis and systemic lupus erythematosus,both of which are autoimmune diseases,suggesting that AAA could be one type of autoimmune diseases in etiology.Based on this observation,we further hypothesized that drugs for autoimmune diseases could be repurposed for the prevention and therapy of AAA.Finally,animal experiments confirmed that methotrexate,a drug for autoimmune diseases,was able to alleviate the formation and development of AAA.