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
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: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 investigate the changes of the plasma level of MMP-9 (Matrix Metalloproteinase-9, MMP-9) in the patients with abdominal aortic aneurysms (AAAs) before and after the treatment, and evaluate the significan...Objective: To investigate the changes of the plasma level of MMP-9 (Matrix Metalloproteinase-9, MMP-9) in the patients with abdominal aortic aneurysms (AAAs) before and after the treatment, and evaluate the significance of MMP-9 in the pathogenesis of AAAs. Methods: Blood samples of 35 patients with AAAs and 10 patients with the arterial occlusive diseases (AODs) , which enrolled into the Vascular Surgery Center of Colonge University Hospital from February to August of 2002, were collected before and one month after surgical repair or less-invasive endovascular exclusion. The plasma concentrations of MMP-9 of all the collected samples were measured by means of enzyme-linked immunosorbent assay(ELISA), and compared between the two groups patients at different time point. Results: The mean plasma concentration of MMP-9 of AAAs was significantly higher than that of AODs prior to treatment [(90.3±9.1) ng/ml vs (23.6±7.3) ng/ml, P<0.05], and no apparent difference was showed in the patients with AODs [(23.6±7.3) ng/ml vs (25.3±5.8) ng/ml, P>0.05)] before and after the surgical bypass operation. However, in the patients with AAAs the plasma concentration of MMP-9 was apparently decreased one month after the surgical repair or endovascular exclusion compared with before [(28.6±8.4) ng/ml vs (90.3±9.1) ng/ml, P<0.05)]. No meaningful difference of the mean plasma MMP-9 concentration was seen between two groups after the both being successfully treated [(28.6±8.4) ng/ml vs (25.3±5.8) ng/ml, P>0.05]. Conclusion: Apparent elevation of plasma concentration of MMP-9 in the AAAs and its dramatic decrease after being treated implicated that MMP-9 might play an important role in the formation and development of AAAs. Meanwhile, to investigate the changes of MMP-9 level of AAAs could provide an practical way to facilitate the earlier diagnosis and long term surveillance for AAAs. More importantly, pharmacologic prevention and treatment of AAAs, in which the MMP-9 serves as effective target, might be possible in the future.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
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
Objective:To investigate the production of nitric oxide(NO) and the expression of inducible nitric oxide synthase (iNOS), and their possible role in abdominal aortic aneurysm (AAA). Methods: A total of 28 pati...Objective:To investigate the production of nitric oxide(NO) and the expression of inducible nitric oxide synthase (iNOS), and their possible role in abdominal aortic aneurysm (AAA). Methods: A total of 28 patients with AAA, 10 healthy controls, and 8 patients with arterial occlusive disease were enrolled into this study. Standard colorimetric assay was used to examine NO concentration in plasma from patients with AAA and normal controls, and in cultured smooth muscle cells (SMCs). Expression of iNOS in aortas and cultured SMCs were detected by immunochemistry. The correlation of iNOS expression with age of the patient, size of aneurysm, and degree of inflammation was also investigated by Cochran-Mantel-Haenszel χ^2 test and Kendall correlation. Results : Expression of iNOS increased significantly in the wall of aneurism in the patients with AAA compared to the healthy controls (P〈0.05) and the patients with occlusive arteries (P〈0.05). iNOS protein and media NOx (nitrite+nitrate) also increased in cultured SMCs from human AAA (n=4, P〈0.05), while plasma NOx decreased in patients with AAA (n= 25) compared to the healthy controls (n=20). There was a positive correlation between iNOS protein and the degree of inflammation in aneurismal wall (Kendall coefficient = 0. 5032, P= 0. 0029). Conclusion: SMCs and inflammatory cells are main cellular sources of increased iNOS in AAA, and NO may play a part in pathogenesis in AAA through inflammation, SMCs and oxidative stress.展开更多
In the study, we sought to retrospectively analyze the effectiveness and safety of surgical repair of thoracoab-dominal aortic aneurysm using the critical artery reattachment technique. Twenty-three consecutive thorac...In the study, we sought to retrospectively analyze the effectiveness and safety of surgical repair of thoracoab-dominal aortic aneurysm using the critical artery reattachment technique. Twenty-three consecutive thoracoab-dominal aortic aneurysm patients were treated using the technique of sequential aortic clamping and critical artery reattachment. The entire procedure was technically successful in all patients. One died of renal failure and the overall hospital mortality was 4.35%. The total incidence of complications was 21.74%. At a median follow-up of 33 months, all patients were alive. We found that the application of critical artery reattachment technique in the management of thoracoabdominal aortic aneurysm provides excellent short- and mid-term results in most patients. It could markedly increase the curing rate and reduce the morbidity of postoperative complications including par-aplegia, ischemia of abdominal viscera, and renal failure.展开更多
Abdominal aortic aneurysm(AAA)is a progressive aortic dilatation,causing~80%mortality upon rupture.Currently,there is no approved drug therapy for AAA.Surgical repairs are invasive and risky and thus not recommended t...Abdominal aortic aneurysm(AAA)is a progressive aortic dilatation,causing~80%mortality upon rupture.Currently,there is no approved drug therapy for AAA.Surgical repairs are invasive and risky and thus not recommended to patients with small AAAs which,however,account for~90%of the newly diagnosed cases.It is therefore a compelling unmet clinical need to discover effective non-invasive strategies to prevent or slow down AAA progression.We contend that the first AAA drug therapy will only arise through discoveries of both effective drug targets and innovative delivery methods.There is substantial evidence that degenerative smooth muscle cells(SMCs)orchestrate AAA pathogenesis and progression.In this study,we made an exciting finding that PERK,the endoplasmic reticulum(ER)stress Protein Kinase R-like ER Kinase,is a potent driver of SMC degeneration and hence a potential therapeutic target.Indeed,local knockdown of PERK in elastase-challenged aorta significantly attenuated AAA lesions in vivo.In parallel,we also conceived a biomimetic nanocluster(NC)design uniquely tailored to AAA-targeting drug delivery.This NC demonstrated excellent AAA homing via a platelet-derived biomembrane coating;and when loaded with a selective PERK inhibitor(PERKi,GSK2656157),the NC therapy conferred remarkable benefits in both preventing aneurysm development and halting the progression of pre-existing aneurysmal lesions in two distinct rodent models of AAA.In summary,our current study not only establishes a new intervention target for mitigating SMC degeneration and aneurysmal pathogenesis,but also provides a powerful tool to facilitate the development of effective drug therapy of AAA.展开更多
BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to exa...BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD.METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95% confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results.RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4% male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women.CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.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
Objectives: This study aimed to determine whether errors in vascular measurements would affect device selection in endovascular aortic repair (EVAR) by comparing measurements obtained using non-contrast computed tomog...Objectives: This study aimed to determine whether errors in vascular measurements would affect device selection in endovascular aortic repair (EVAR) by comparing measurements obtained using non-contrast computed tomography (NCT) with those obtained using contrast-enhanced CT (CECT). Materials and Methods: This single-center, retrospective study included 25 patients who underwent EVAR for abdominal aortic aneurysm at our institution. A 1-mm horizontal cross-sectional slice of NCT and CECT from each patient was retrospectively reviewed. The area from the abdominal aorta to the common iliac artery was divided into four zones. A centerline was created using the NCT by manually plotting the center points. Subsequently, the centerlines were automatically extracted and manually corrected during the arterial phase of CECT. The diameter and length of each zone were measured for each modality. The mean diameters and lengths of the target vessels were compared between NCT and CECT. Results: The measurements obtained using both methods were reproducible and demonstrated good agreement. The mean differences in vessel length and diameter measurements for each segment between NCT and CECT were not statistically significant, indicating good consistency. Conclusion: NCT may be useful for preoperative EVAR evaluation in patients with renal dysfunction or allergies to contrast agents.展开更多
Angiotensin II (Angll) is the primary bioactive peptide of the renin angiotensin system that plays a critical role in many cardiovascular diseases. Subcutaneous infusion of Angll into mice induces the development of...Angiotensin II (Angll) is the primary bioactive peptide of the renin angiotensin system that plays a critical role in many cardiovascular diseases. Subcutaneous infusion of Angll into mice induces the development of abdominal aortic aneurysms (AAAs). Like human AAAs, Angll-induced AAA tissues exhibit progressive changes and considerable heterogeneity. This complex pathology provides an impediment to the quantification of aneurysmal tissue composition by biochemical and immunostaining techniques. Therefore, while the mouse model of Angll-induced AAAs provides a salutary approach to studying the mechanisms of the evolution of AAAs in humans, meaningful interpretation of mechanisms requires consideration of the heterogeneous nature of the diseased tissue.展开更多
Aortic aneurysms are common and life threatening problems with high rates of death.The initiation and progression of aneurysms are characterized by extensive extracellular matrix degradation and immune cells invasion ...Aortic aneurysms are common and life threatening problems with high rates of death.The initiation and progression of aneurysms are characterized by extensive extracellular matrix degradation and immune cells invasion within arterial wall.During the pathogenesis of all aneurysms,inflammation and immune cells play a significant role.Although T cells are abundant in aneurysm tissue,their functions in initiation and propagation of aneurysms remain unclear.This review summarizes the current state of knowledge of T lymphocytes on this disease and focuses on potential mechanisms of specific T cell responses.展开更多
The unfavorable vessel anatomy is still a major challenge in the endovascular aneurysm repair,with usually insufficient or even no proximal/distal landing zone for the stent-graft.During recent years,several articles ...The unfavorable vessel anatomy is still a major challenge in the endovascular aneurysm repair,with usually insufficient or even no proximal/distal landing zone for the stent-graft.During recent years,several articles have been published concerning the new approach of multiple stents to the treatment of aneurysm by reducing the stent porosity to encourage laminar flow,preserving branch patency,and promoting thrombus formation in the aneurysm.1,2 We herein report the use of multiple overlapping stents in the treatment of thoracoabdominal aortic aneurysms.展开更多
An abdominal aortic aneurysm(AAA) is a permanent, localized dilatation of the abdominal aorta. In western countries, the morbidity of AAA is approximately 8%. Currently, pharmacotherapies for AAA are limited. Here, we...An abdominal aortic aneurysm(AAA) is a permanent, localized dilatation of the abdominal aorta. In western countries, the morbidity of AAA is approximately 8%. Currently, pharmacotherapies for AAA are limited. Here, we demonstrate that baicalein(BAI), the main component of the Chinese traditional drug "Huang Qin", attenuates the incidence and severity of AAA in Apoe儃/儃 mice infused with angiotensin II(AngII). Mechanically, BAI treatment decreases AngII-induced reactive oxygen species(ROS) production in the aortic wall. Moreover, BAI inhibits inflammatory cell accumulation in the aortas of mice infused with AngII. It also inhibits AngII-induced activation of matrix metalloproteinase 2(MMP-2) and MMP-9 to maintain elastin content in vivo. In addition, it blocks AngII cascade by downregulating angiotensin type 1 receptor(AT1R) and inhibiting mitogen-activated protein kinases(MAPKs). Taken together, our findings show that BAI is an effective agent for AAA prevention.展开更多
Background Nitric oxide (NO) is an important mediator in the pathophysiology of many vascular diseases. However, the definite role of NO in human abdominal aortic aneurysm (AAA) formation is unclear. The aim of th...Background Nitric oxide (NO) is an important mediator in the pathophysiology of many vascular diseases. However, the definite role of NO in human abdominal aortic aneurysm (AAA) formation is unclear. The aim of this study was to investigate production of NO and expression of inducible nitric oxide synthase (iNOS), and their possible role in AAA. Methods A total of 28 patients with AAA, 10 healthy controls, and 8 patients with arterial occlusive disease were enrolled into this study. Standard colorimetric assay was used to examine NO concentration in plasma from patients with AAA and normal controls, and in cultured smooth muscle cells (SMCs). Expression of iNOS in aortas and cultured SMCs were detected by immunochemistry. The correlation of iNOS expression with age of the patient, size of aneurysm, and degree of inflammation was also investigated by Cochran-Mantel-HaenszelX^2 test and Kendall' Tau correlation. Results Expression of iNOS increased significantly in the wall of aneurism in the patients with AAA compared to the healthy controls (P〈0.05) and the patients with occlusive arteries (P〈0.05). iNOS protein and media NOx (nitrite+nitrate) also increased in cultured SMCs from human AAA (n=4, P〈0.05), while plasma NOx decreased in patients with AAA (n=25) compared to the healthy controls (n=20). There was a positive correlation between iNOS protein and degree of inflammation in aneurismal wall (Kendall coefficient=0.5032, P=0.0029) Conclusions SMCs and inflammatory cells were main cellular sources of increased iNOS in AAA, and NO may play a part in pathogenesis in AAA through inflammation.展开更多
Background Although it is generally acknowledged that patients with ruptured abdominal aortic aneurysm (rAAA) obtain the greatest benefit from endovascular repair (EVAR), convincing evidence on the medium-long ter...Background Although it is generally acknowledged that patients with ruptured abdominal aortic aneurysm (rAAA) obtain the greatest benefit from endovascular repair (EVAR), convincing evidence on the medium-long term effect is lacking. The aim of this study was to compare and summarize published results of rAAA that underwent EVAR with open surgical repair (OSR). Methods A search of publicly published literature was performed. Based on an inclusion and exclusion criteria, a systematic meta-analysis was undertaken to compare patient characteristics, complications, short term mortality and medium-long term outcomes. A random-effects model was used to pool the data and calculate pooled odds ratios and weighted mean differences. A quantitative method was used to analyze the differences between these two methods. Results A search of the published literature showed that fourteen English language papers comprising totally 1213 patients with rAAA (435 EVAR and 778 OSR) would be suitable for this study. Furthermore, 13 Chinese studies were included, including 267 patients with rAAA totally, among which 238 patients received operation. The endovascular method was associated with more respiratory diseases before treatment (OR=1.81, P=0.01), while there are more patients with hemodynamic instability before treatment in OSR group (OR=1.53, P=0.031). Mean blood transfusion was 1328 ml for EVAR and 2809 ml for OSR (weighted mean difference (WMD) 1500 ml, P=0.014). The endovascular method was associated with a shorter stay in intensive care (WMD 2.34 days, P 〈0.001) and a shorter total post- operative stay (WMD 6.27 days, P 〈0.001). The pooled post-operative complication rate of respiratory system and visceral ischemia seldom occurred in the EVAR group (OR=0.48, P 〈0.001 and OR=0.28, P=0.043, respectively). The pooled 30-day mortality was 25.7% for EVAR and 39.6% for OSR, and the odds ratio was 0.53 (95% confidence interval (CI) 0.41-0.70, P 〈0.001). There was not, however, any significant reduction in the medium-long all-cause mortality rate (HR=1.13, P=0.381) and re-intervention rate (OR= 2.19, ,~=-0.243) following EVAR. In EVAR group, nevertheless, incidence of type I endoleak was significantly lower than type II endoleak (OR=0.33, P=0.039) at late follow-up period. Conclusions On the basis of this systematic review, rAAA EVAR results in less blood use for transfusion, shorter operation time, shorter intensive care unit and hospital stays, and lower 30-day mortality. However, in the medium-long term, it is not associated with a reduction in all-cause mortality.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.
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.
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 investigate the changes of the plasma level of MMP-9 (Matrix Metalloproteinase-9, MMP-9) in the patients with abdominal aortic aneurysms (AAAs) before and after the treatment, and evaluate the significance of MMP-9 in the pathogenesis of AAAs. Methods: Blood samples of 35 patients with AAAs and 10 patients with the arterial occlusive diseases (AODs) , which enrolled into the Vascular Surgery Center of Colonge University Hospital from February to August of 2002, were collected before and one month after surgical repair or less-invasive endovascular exclusion. The plasma concentrations of MMP-9 of all the collected samples were measured by means of enzyme-linked immunosorbent assay(ELISA), and compared between the two groups patients at different time point. Results: The mean plasma concentration of MMP-9 of AAAs was significantly higher than that of AODs prior to treatment [(90.3±9.1) ng/ml vs (23.6±7.3) ng/ml, P<0.05], and no apparent difference was showed in the patients with AODs [(23.6±7.3) ng/ml vs (25.3±5.8) ng/ml, P>0.05)] before and after the surgical bypass operation. However, in the patients with AAAs the plasma concentration of MMP-9 was apparently decreased one month after the surgical repair or endovascular exclusion compared with before [(28.6±8.4) ng/ml vs (90.3±9.1) ng/ml, P<0.05)]. No meaningful difference of the mean plasma MMP-9 concentration was seen between two groups after the both being successfully treated [(28.6±8.4) ng/ml vs (25.3±5.8) ng/ml, P>0.05]. Conclusion: Apparent elevation of plasma concentration of MMP-9 in the AAAs and its dramatic decrease after being treated implicated that MMP-9 might play an important role in the formation and development of AAAs. Meanwhile, to investigate the changes of MMP-9 level of AAAs could provide an practical way to facilitate the earlier diagnosis and long term surveillance for AAAs. More importantly, pharmacologic prevention and treatment of AAAs, in which the MMP-9 serves as effective target, might be possible in the future.
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.
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Supported by the National Natural Science Foundation of China (No. 39800177)
文摘Objective:To investigate the production of nitric oxide(NO) and the expression of inducible nitric oxide synthase (iNOS), and their possible role in abdominal aortic aneurysm (AAA). Methods: A total of 28 patients with AAA, 10 healthy controls, and 8 patients with arterial occlusive disease were enrolled into this study. Standard colorimetric assay was used to examine NO concentration in plasma from patients with AAA and normal controls, and in cultured smooth muscle cells (SMCs). Expression of iNOS in aortas and cultured SMCs were detected by immunochemistry. The correlation of iNOS expression with age of the patient, size of aneurysm, and degree of inflammation was also investigated by Cochran-Mantel-Haenszel χ^2 test and Kendall correlation. Results : Expression of iNOS increased significantly in the wall of aneurism in the patients with AAA compared to the healthy controls (P〈0.05) and the patients with occlusive arteries (P〈0.05). iNOS protein and media NOx (nitrite+nitrate) also increased in cultured SMCs from human AAA (n=4, P〈0.05), while plasma NOx decreased in patients with AAA (n= 25) compared to the healthy controls (n=20). There was a positive correlation between iNOS protein and the degree of inflammation in aneurismal wall (Kendall coefficient = 0. 5032, P= 0. 0029). Conclusion: SMCs and inflammatory cells are main cellular sources of increased iNOS in AAA, and NO may play a part in pathogenesis in AAA through inflammation, SMCs and oxidative stress.
文摘In the study, we sought to retrospectively analyze the effectiveness and safety of surgical repair of thoracoab-dominal aortic aneurysm using the critical artery reattachment technique. Twenty-three consecutive thoracoab-dominal aortic aneurysm patients were treated using the technique of sequential aortic clamping and critical artery reattachment. The entire procedure was technically successful in all patients. One died of renal failure and the overall hospital mortality was 4.35%. The total incidence of complications was 21.74%. At a median follow-up of 33 months, all patients were alive. We found that the application of critical artery reattachment technique in the management of thoracoabdominal aortic aneurysm provides excellent short- and mid-term results in most patients. It could markedly increase the curing rate and reduce the morbidity of postoperative complications including par-aplegia, ischemia of abdominal viscera, and renal failure.
基金supported by the National Institute of Health(NIH)grants R01HL133665(to L.-W.G.),R01HL143469R01HL129785(to K.C.K,S.G.,and L.-W.G.)+2 种基金R01HL162895(to B.W.)R01HL132395 and 1S10RR027333(to J.A.H.)Overseas Research Fellowships,The Uehara Memorial Foundation in Japan(to T.S.).
文摘Abdominal aortic aneurysm(AAA)is a progressive aortic dilatation,causing~80%mortality upon rupture.Currently,there is no approved drug therapy for AAA.Surgical repairs are invasive and risky and thus not recommended to patients with small AAAs which,however,account for~90%of the newly diagnosed cases.It is therefore a compelling unmet clinical need to discover effective non-invasive strategies to prevent or slow down AAA progression.We contend that the first AAA drug therapy will only arise through discoveries of both effective drug targets and innovative delivery methods.There is substantial evidence that degenerative smooth muscle cells(SMCs)orchestrate AAA pathogenesis and progression.In this study,we made an exciting finding that PERK,the endoplasmic reticulum(ER)stress Protein Kinase R-like ER Kinase,is a potent driver of SMC degeneration and hence a potential therapeutic target.Indeed,local knockdown of PERK in elastase-challenged aorta significantly attenuated AAA lesions in vivo.In parallel,we also conceived a biomimetic nanocluster(NC)design uniquely tailored to AAA-targeting drug delivery.This NC demonstrated excellent AAA homing via a platelet-derived biomembrane coating;and when loaded with a selective PERK inhibitor(PERKi,GSK2656157),the NC therapy conferred remarkable benefits in both preventing aneurysm development and halting the progression of pre-existing aneurysmal lesions in two distinct rodent models of AAA.In summary,our current study not only establishes a new intervention target for mitigating SMC degeneration and aneurysmal pathogenesis,but also provides a powerful tool to facilitate the development of effective drug therapy of AAA.
基金supported by grants from the Ministry of Science and Technology of the People’s Republic of China,(No.2020AAA0109605 to XL)grants from the National Natural Science Foundation of China(No.82272246 and 82072225 to XL)+1 种基金Science and Technology Program of Guangzhou,China(No.202206010044 to XL)High-level Hospital Construction Project of Guangdong Provincial People’s Hospital(No.DFJHBF202104 to XL).
文摘BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD.METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95% confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results.RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4% male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women.CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.
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Objectives: This study aimed to determine whether errors in vascular measurements would affect device selection in endovascular aortic repair (EVAR) by comparing measurements obtained using non-contrast computed tomography (NCT) with those obtained using contrast-enhanced CT (CECT). Materials and Methods: This single-center, retrospective study included 25 patients who underwent EVAR for abdominal aortic aneurysm at our institution. A 1-mm horizontal cross-sectional slice of NCT and CECT from each patient was retrospectively reviewed. The area from the abdominal aorta to the common iliac artery was divided into four zones. A centerline was created using the NCT by manually plotting the center points. Subsequently, the centerlines were automatically extracted and manually corrected during the arterial phase of CECT. The diameter and length of each zone were measured for each modality. The mean diameters and lengths of the target vessels were compared between NCT and CECT. Results: The measurements obtained using both methods were reproducible and demonstrated good agreement. The mean differences in vessel length and diameter measurements for each segment between NCT and CECT were not statistically significant, indicating good consistency. Conclusion: NCT may be useful for preoperative EVAR evaluation in patients with renal dysfunction or allergies to contrast agents.
基金Project (Nos. HL062846 and HL80100) supported by the National Institutes of Health of the United States of America
文摘Angiotensin II (Angll) is the primary bioactive peptide of the renin angiotensin system that plays a critical role in many cardiovascular diseases. Subcutaneous infusion of Angll into mice induces the development of abdominal aortic aneurysms (AAAs). Like human AAAs, Angll-induced AAA tissues exhibit progressive changes and considerable heterogeneity. This complex pathology provides an impediment to the quantification of aneurysmal tissue composition by biochemical and immunostaining techniques. Therefore, while the mouse model of Angll-induced AAAs provides a salutary approach to studying the mechanisms of the evolution of AAAs in humans, meaningful interpretation of mechanisms requires consideration of the heterogeneous nature of the diseased tissue.
基金supported by the National Basic Research Program of China(2013CB531103,2012CB517805)National Natural Science Foundation of China(81222002,91339118)
文摘Aortic aneurysms are common and life threatening problems with high rates of death.The initiation and progression of aneurysms are characterized by extensive extracellular matrix degradation and immune cells invasion within arterial wall.During the pathogenesis of all aneurysms,inflammation and immune cells play a significant role.Although T cells are abundant in aneurysm tissue,their functions in initiation and propagation of aneurysms remain unclear.This review summarizes the current state of knowledge of T lymphocytes on this disease and focuses on potential mechanisms of specific T cell responses.
文摘The unfavorable vessel anatomy is still a major challenge in the endovascular aneurysm repair,with usually insufficient or even no proximal/distal landing zone for the stent-graft.During recent years,several articles have been published concerning the new approach of multiple stents to the treatment of aneurysm by reducing the stent porosity to encourage laminar flow,preserving branch patency,and promoting thrombus formation in the aneurysm.1,2 We herein report the use of multiple overlapping stents in the treatment of thoracoabdominal aortic aneurysms.
基金supported by the National Natural Science Foundation of China(31571193,81422002,91339201)
文摘An abdominal aortic aneurysm(AAA) is a permanent, localized dilatation of the abdominal aorta. In western countries, the morbidity of AAA is approximately 8%. Currently, pharmacotherapies for AAA are limited. Here, we demonstrate that baicalein(BAI), the main component of the Chinese traditional drug "Huang Qin", attenuates the incidence and severity of AAA in Apoe儃/儃 mice infused with angiotensin II(AngII). Mechanically, BAI treatment decreases AngII-induced reactive oxygen species(ROS) production in the aortic wall. Moreover, BAI inhibits inflammatory cell accumulation in the aortas of mice infused with AngII. It also inhibits AngII-induced activation of matrix metalloproteinase 2(MMP-2) and MMP-9 to maintain elastin content in vivo. In addition, it blocks AngII cascade by downregulating angiotensin type 1 receptor(AT1R) and inhibiting mitogen-activated protein kinases(MAPKs). Taken together, our findings show that BAI is an effective agent for AAA prevention.
基金This study was supported by a grant from Clinical Medical Center of Vascular Surgery in Shanghai (NO. ZX03B1).
文摘Background Nitric oxide (NO) is an important mediator in the pathophysiology of many vascular diseases. However, the definite role of NO in human abdominal aortic aneurysm (AAA) formation is unclear. The aim of this study was to investigate production of NO and expression of inducible nitric oxide synthase (iNOS), and their possible role in AAA. Methods A total of 28 patients with AAA, 10 healthy controls, and 8 patients with arterial occlusive disease were enrolled into this study. Standard colorimetric assay was used to examine NO concentration in plasma from patients with AAA and normal controls, and in cultured smooth muscle cells (SMCs). Expression of iNOS in aortas and cultured SMCs were detected by immunochemistry. The correlation of iNOS expression with age of the patient, size of aneurysm, and degree of inflammation was also investigated by Cochran-Mantel-HaenszelX^2 test and Kendall' Tau correlation. Results Expression of iNOS increased significantly in the wall of aneurism in the patients with AAA compared to the healthy controls (P〈0.05) and the patients with occlusive arteries (P〈0.05). iNOS protein and media NOx (nitrite+nitrate) also increased in cultured SMCs from human AAA (n=4, P〈0.05), while plasma NOx decreased in patients with AAA (n=25) compared to the healthy controls (n=20). There was a positive correlation between iNOS protein and degree of inflammation in aneurismal wall (Kendall coefficient=0.5032, P=0.0029) Conclusions SMCs and inflammatory cells were main cellular sources of increased iNOS in AAA, and NO may play a part in pathogenesis in AAA through inflammation.
基金This work was supported by Science Foundation of China grants from the National Natural (No. 304717076), the Department of Education of Liaoning Province (Key Laboratory Project No. LS2010172), and Ministry of Education of China (Key Research Project of Science and Technology No. 208028).
文摘Background Although it is generally acknowledged that patients with ruptured abdominal aortic aneurysm (rAAA) obtain the greatest benefit from endovascular repair (EVAR), convincing evidence on the medium-long term effect is lacking. The aim of this study was to compare and summarize published results of rAAA that underwent EVAR with open surgical repair (OSR). Methods A search of publicly published literature was performed. Based on an inclusion and exclusion criteria, a systematic meta-analysis was undertaken to compare patient characteristics, complications, short term mortality and medium-long term outcomes. A random-effects model was used to pool the data and calculate pooled odds ratios and weighted mean differences. A quantitative method was used to analyze the differences between these two methods. Results A search of the published literature showed that fourteen English language papers comprising totally 1213 patients with rAAA (435 EVAR and 778 OSR) would be suitable for this study. Furthermore, 13 Chinese studies were included, including 267 patients with rAAA totally, among which 238 patients received operation. The endovascular method was associated with more respiratory diseases before treatment (OR=1.81, P=0.01), while there are more patients with hemodynamic instability before treatment in OSR group (OR=1.53, P=0.031). Mean blood transfusion was 1328 ml for EVAR and 2809 ml for OSR (weighted mean difference (WMD) 1500 ml, P=0.014). The endovascular method was associated with a shorter stay in intensive care (WMD 2.34 days, P 〈0.001) and a shorter total post- operative stay (WMD 6.27 days, P 〈0.001). The pooled post-operative complication rate of respiratory system and visceral ischemia seldom occurred in the EVAR group (OR=0.48, P 〈0.001 and OR=0.28, P=0.043, respectively). The pooled 30-day mortality was 25.7% for EVAR and 39.6% for OSR, and the odds ratio was 0.53 (95% confidence interval (CI) 0.41-0.70, P 〈0.001). There was not, however, any significant reduction in the medium-long all-cause mortality rate (HR=1.13, P=0.381) and re-intervention rate (OR= 2.19, ,~=-0.243) following EVAR. In EVAR group, nevertheless, incidence of type I endoleak was significantly lower than type II endoleak (OR=0.33, P=0.039) at late follow-up period. Conclusions On the basis of this systematic review, rAAA EVAR results in less blood use for transfusion, shorter operation time, shorter intensive care unit and hospital stays, and lower 30-day mortality. However, in the medium-long term, it is not associated with a reduction in all-cause mortality.