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 histolo...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.展开更多
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...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.展开更多
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 responsibili...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.展开更多
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...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.展开更多
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 t...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.展开更多
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,a...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.展开更多
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...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.展开更多
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...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.展开更多
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 repa...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.展开更多
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 an...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.展开更多
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 managem...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.展开更多
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-/-)...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.展开更多
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...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.展开更多
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 ...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.展开更多
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...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.展开更多
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 m...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.展开更多
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 Syste...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.展开更多
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 ...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.展开更多
Objective. To describe our surgical experience on rupture of abdominal aortic aneurysm .Methods. Two cases of ruptured aortic aneurysms with severe complication were analyzed. Aorta reconstruction procedures were perf...Objective. To describe our surgical experience on rupture of abdominal aortic aneurysm .Methods. Two cases of ruptured aortic aneurysms with severe complication were analyzed. Aorta reconstruction procedures were performed using bifurcated e-PTFE grafts during emergency operation. Diagnosis, preoperadve resuscitation, emergency surgical intervention, and postoperative complications of these patients were summarized and discussed.Results. Rupture of aortic aneurysm in both patients presented as a huge retroperitoneum haematoma by computed tomography scan. They were successfully saved by prompt body fluid compensation, emergency procedure, intraoperative resuscitation, and postoperative intensive care.Conclusions. Correct diagnosis, prompt surgical management, immediate intraoperative proximal aorta clamping during procedure, and effective management of postoperative complications were the key points to successful treatment of ruptured aortic aneurysm.展开更多
Background Abdominal aortic aneurysm (AAA) is a multifactorial disease with strong genetic components. Various genetic loci have been associated with clinical AAA, but few studies have investigated pathological AAA,...Background Abdominal aortic aneurysm (AAA) is a multifactorial disease with strong genetic components. Various genetic loci have been associated with clinical AAA, but few studies have investigated pathological AAA, an intermediate phenotype of the disease. Methods We examined 2263 consecutive autopsies of older Japanese subjects from a study on geriatric diseases in Japanese individuals (The JG-SNP study). The presence of AAA was determined with a pathological diagnosis during autopsy. Single nucleotide variants (SNVs) associated with AAA were determined with an Illumina HumanExome Beadchip array. Logistic regression analyses were performed to determine ge- netic associations. Age, gender, and other risk factors of AAA were analyzed as covariates. Results 118 subjects with AAA and 2145 sub- jects without AAA were analyzed in a case-control setting. No variants reached significance after applying the Bonferroni correction (P 〈 2.05×10^-6). The strongest associations were found with rs3750092 (p.E321G, OR: 0.36, 95% CI: 0.24-0.56, P = 6.09 ×10^-6), a variant in the WAS/WASL interacting protein family 3 (WIPF3), and with rs1051338 (p.T16P, OR: 2.50, 95% CI: 1.70-3.66, P = 2.79 ×10^-6) and rs2246942 (intronic, OR: 2.32, 95% CI: 1.58-3.41, P = 1.61 ×10^-5), variants in the lysosomal acid lipase A (LIPA). LIPA is essential for macrophage cholesterol metabolism. Immunohistological analyses of WIPF3 protein in AAA samples from three subjects revealed that WIPF3 was expressed in macrophages ofatheromatous plaques. Conclusions This study suggests that WIPF3 and LIPA, both of which are expressed in the macrophages are involved in pathological AAA. These results should be regarded as hypothesis-generating; thus, replication study is warranted.展开更多
基金supported by Shaanxi Provincial Natural Science Foundation(2023-CX-PT-17 to Sihai Zhao)Natural Science Foundation of Xi'an Jiaotong University Foundation(YXJLRH2022073 to Sihai Zhao)Project of Key Laboratory of Medical Large Animal Models of Guangdong Province(Klmlam 202204 to Sihai Zhao)。
文摘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.
文摘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.
文摘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.
文摘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.
基金the National Natural Science Foundation of China(No.81900432)the Science Foundation of Union Hospital(No.F016.02004.21003.124).
文摘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.
文摘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.
基金The project was supported by the National Natural Science Foundation of China(10672090)
文摘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.
基金supported by a grant from the Key Program of Scientific and Technological Research of Wuhan (No. 200862123565)
文摘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.
文摘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.
文摘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.
文摘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.
基金supported by grants from the National Natural Science Foundation of China(No.81570325)the Fundamental Research Funds for the Central Universities
文摘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.
文摘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.
基金supported by the grants from National Natural Science Foundation of China(No.81100226,31300889,91439127,and 81570435)
文摘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.
基金supported by grants from the National Natural Science Foundation of China(No.81770478 and No.81970395)the Shanghai Science and Technology Development Foundation(No.21S21901900)+1 种基金Inter-governmental Science and Technology Innovation Cooperation Program,Ministry of Science and Technology of China(No.2021YFE0111300)the Biological Resources Programme,Chinese Academy of Sciences(No.KFJ-BRP-008).
文摘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.
基金partly supported by grants from the Natural Science Foundation of Shaanxi Province (2020PT-004, 2017BSHQYXMZZ18 and 2021PT-056)the National Natural Science Foundation of China (82070470 and 81370379)
文摘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.
文摘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.
基金Supported by the Peking Union Medical Foundation-Rui E(Rui Yi)Emergency Medical Research Special Fund,No.R2018001the Beijing Science and Technology Association Jinqiao Project Seed Fund,No.JQ18057.
文摘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.
文摘Objective. To describe our surgical experience on rupture of abdominal aortic aneurysm .Methods. Two cases of ruptured aortic aneurysms with severe complication were analyzed. Aorta reconstruction procedures were performed using bifurcated e-PTFE grafts during emergency operation. Diagnosis, preoperadve resuscitation, emergency surgical intervention, and postoperative complications of these patients were summarized and discussed.Results. Rupture of aortic aneurysm in both patients presented as a huge retroperitoneum haematoma by computed tomography scan. They were successfully saved by prompt body fluid compensation, emergency procedure, intraoperative resuscitation, and postoperative intensive care.Conclusions. Correct diagnosis, prompt surgical management, immediate intraoperative proximal aorta clamping during procedure, and effective management of postoperative complications were the key points to successful treatment of ruptured aortic aneurysm.
文摘Background Abdominal aortic aneurysm (AAA) is a multifactorial disease with strong genetic components. Various genetic loci have been associated with clinical AAA, but few studies have investigated pathological AAA, an intermediate phenotype of the disease. Methods We examined 2263 consecutive autopsies of older Japanese subjects from a study on geriatric diseases in Japanese individuals (The JG-SNP study). The presence of AAA was determined with a pathological diagnosis during autopsy. Single nucleotide variants (SNVs) associated with AAA were determined with an Illumina HumanExome Beadchip array. Logistic regression analyses were performed to determine ge- netic associations. Age, gender, and other risk factors of AAA were analyzed as covariates. Results 118 subjects with AAA and 2145 sub- jects without AAA were analyzed in a case-control setting. No variants reached significance after applying the Bonferroni correction (P 〈 2.05×10^-6). The strongest associations were found with rs3750092 (p.E321G, OR: 0.36, 95% CI: 0.24-0.56, P = 6.09 ×10^-6), a variant in the WAS/WASL interacting protein family 3 (WIPF3), and with rs1051338 (p.T16P, OR: 2.50, 95% CI: 1.70-3.66, P = 2.79 ×10^-6) and rs2246942 (intronic, OR: 2.32, 95% CI: 1.58-3.41, P = 1.61 ×10^-5), variants in the lysosomal acid lipase A (LIPA). LIPA is essential for macrophage cholesterol metabolism. Immunohistological analyses of WIPF3 protein in AAA samples from three subjects revealed that WIPF3 was expressed in macrophages ofatheromatous plaques. Conclusions This study suggests that WIPF3 and LIPA, both of which are expressed in the macrophages are involved in pathological AAA. These results should be regarded as hypothesis-generating; thus, replication study is warranted.