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Degradation phenomena on last generations of polyethylene terephthalate knitted vascular prostheses 上代聚对苯二甲酸乙二醇酯编织血管假体的降解现象
Q3 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jvssci.2023.01.001
Arielle Bellissard MD , Nabil Chakfe MD, PhD , Salomé Kuntz MD, MSc , Delphine Dion MSc , Lory Schmitt , Frédéric Heim PhD , Anne Lejay MD, PhD

Objectives

The aim of this study was to analyze a series of new generations of explanted knitted polyethylene terephthalate (PET) vascular grafts (VGs) presenting nonanastomotic degradations according to preoperative computed tomography angiography (CTA) when available in order to better understand the mechanisms leading to rupture.

Methods

Explanted knitted PET VGs were collected as part of the Geprovas European Collaborative Retrieval Program. VGs implanted after 1990 presenting a nonanastomotic rupture of the fabric were included. Clinical data and pre-explantation CTA data when available were retrieved for each VG. The ruptures were characterized by macroscopic examination and optical microscopy according to a standardized protocol.

Results

Nineteen explants were collected across 11 European centers, 13 were implanted as infrainguinal bypasses, 3 at the aortic level, and 1 as an axillobifemoral bypass. The mean implantation duration was 9.2 years. Pre-explantation CTA data were available for 8 VGs and showed false aneurysms at the adductor canal level on 4 VGs, at the inguinal ligament level on 2 VGs, and in the proximal or middle third thigh level on 3 VGs. Examination revealed longitudinal ruptures on 9 explanted VGs (EVGs), transversal ruptures on 15 EVGs, 45°-oriented ruptures on 5 EVGs, V-shaped ruptures on 7 EVGs, and punctiform ruptures on 2 EVGs. Ruptures involved the remeshing line on 11 EVGs, the guideline on 10 EVGs, and the crimping valley on 15 EVGs.

At the microscopic level, two main degradation phenomena could be identified: a decrease in the density of the meshing and local ruptures of the PET fibers. Fourteen EVGs presented a loosening of the remeshing line and 17 EVGs an attenuation of the crimping.

Conclusions

New-generation PET VG degradation seems to result from both anatomic constraints and intrinsic textile structure phenomena.

目的分析新一代外植针织聚对苯二甲酸乙二醇酯(PET)血管(VGs)在术前ct血管造影(CTA)检查中出现的非吻合口退化,以便更好地了解导致血管破裂的机制。方法在Geprovas欧洲协同检索计划中收集植入的针织PET VGs。包括1990年以后植入的出现非吻合口断裂的VGs。检索每个VG的临床数据和移植前CTA数据。根据标准方案,通过宏观检查和光学显微镜对破裂进行表征。结果在欧洲11个中心收集了19个移植体,其中13个作为腹股沟下旁路植入,3个作为主动脉水平植入,1个作为腋叶-道德旁路植入。平均植入时间为9.2年。移植前CTA数据显示,4个假动脉瘤位于内收管水平,2个假动脉瘤位于腹股沟韧带水平,3个假动脉瘤位于大腿近端或中段。检查结果显示,外植性肺叶纵向破裂9例,横向破裂15例,45°定向破裂5例,v型破裂7例,点状破裂2例。破裂涉及11个evg的重网格线,10个evg的指导线,15个evg的压溃谷。在微观层面上,可以确定两种主要的降解现象:网格密度的降低和PET纤维的局部断裂。14个evg表现为网格线松动,17个evg表现为卷曲衰减。结论新一代PET VG降解可能是解剖约束和内在纺织结构现象共同作用的结果。
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引用次数: 0
Machine learning analysis of confounding variables of a convolutional neural network specific for abdominal aortic aneurysms 腹主动脉瘤专用卷积神经网络混杂变量的机器学习分析
Q3 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jvssci.2022.11.004
Roger T. Tomihama MD , Justin R. Camara MD , Sharon C. Kiang MD

Objective

To identify confounding variables influencing the accuracy of a convolutional neural network (CNN) specific for infrarenal abdominal aortic aneurysms (AAAs) on computed tomography angiograms (CTAs).

Methods

A Health Insurance Portability and Accountability Act-compliant, institutional review board-approved, retrospective study analyzed abdominopelvic CTA scans from 200 patients with infrarenal AAAs and 200 propensity-matched control patients. An AAA-specific trained CNN was developed by the application of transfer learning to the VGG-16 base model using model training, validation, and testing techniques. Model accuracy and area under the curve were analyzed based on data sets (selected, balanced, or unbalanced), aneurysm size, extra-abdominal extension, dissections, and mural thrombus. Misjudgments were analyzed by review of heatmaps, via gradient weighted class activation, overlaid on CTA images.

Results

The trained custom CNN model reported high test group accuracies of 94.1%, 99.1%, and 99.6% and area under the curve of 0.9900, 0.9998, and 0.9993 in selected (n = 120), balanced (n = 3704), and unbalanced image sets (n = 31,899), respectively. Despite an eightfold difference between balanced and unbalanced image sets, the CNN model demonstrated high test group sensitivities (98.7% vs 98.9%) and specificities (99.7% vs 99.3%) in unbalanced and balanced image sets, respectively. For aneurysm size, the CNN model demonstrates decreasing misjudgments as aneurysm size increases: 47% (16/34) for aneurysms <3.3 cm, 32% (11/34) for aneurysms 3.3 to 5 cm, and 20% (7/34) for aneurysms >5 cm. Aneurysms containing measurable mural thrombus were over-represented within type II (false-negative) misjudgments compared with type I (false-positive) misjudgments (71% vs 15%, P < .05). Inclusion of extra-abdominal aneurysm extension (thoracic or iliac artery) or dissection flaps in these imaging sets did not decrease the model's overall accuracy, indicating that the model performance was excellent without the need to clean the data set of confounding or comorbid diagnoses.

Conclusions

Analysis of an AAA-specific CNN model can accurately screen and identify infrarenal AAAs on CTA despite varying pathology and quantitative data sets. The highest anatomic misjudgments were with small aneurysms (<3.3 cm) or the presence of mural thrombus. Accuracy of the CNN model is maintained despite the inclusion of extra-abdominal pathology and imbalanced data sets.

目的确定影响肾下腹主动脉瘤(AAAs)特异性卷积神经网络(CNN)在计算机断层扫描血管造影(CTA)中准确性的混杂变量,这项回顾性研究分析了200名肾下AAAs患者和200名倾向匹配的对照患者的腹部-骨盆CTA扫描结果。通过将迁移学习应用于VGG-16基础模型,使用模型训练、验证和测试技术,开发了AAA特定训练的CNN。根据数据集(选定的、平衡的或不平衡的)、动脉瘤大小、腹外扩张、夹层和附壁血栓分析模型的准确性和曲线下面积。通过回顾热图,通过梯度加权类激活,叠加在CTA图像上,分析误判。结果训练的自定义CNN模型在选定(n=120)、平衡(n=3704)和不平衡图像集(n=31899)中的测试组准确率分别为94.1%、99.1%和99.6%,曲线下面积分别为0.9900、0.9998和0.9993。尽管平衡和不平衡图像集之间存在八倍的差异,但CNN模型在不平衡和平衡图像集中分别表现出较高的测试组敏感性(98.7%对98.9%)和特异性(99.7%对99.3%)。对于动脉瘤大小,CNN模型显示,随着动脉瘤大小的增加,误判减少:47%(16/34)的动脉瘤<;3.3厘米,动脉瘤3.3至5厘米占32%(11/34),动脉瘤占20%(7/34)>;5厘米。与I型(假阳性)误判相比,包含可测量附壁血栓的动脉瘤在II型(假阴性)误判中表现过度(71%对15%,P<;.05)。在这些成像集中包括腹外动脉瘤延伸(胸动脉或髂动脉)或夹层皮瓣并没有降低模型的总体准确性,表明该模型性能优异,而无需清除混杂或共病诊断的数据集。结论尽管病理学和定量数据集各不相同,但对AAA特异性CNN模型的分析可以在CTA上准确筛选和识别肾下AAAs。最高的解剖误判是小动脉瘤(<3.3厘米)或附壁血栓的存在。尽管包含了腹部外病理学和不平衡的数据集,CNN模型的准确性仍然保持不变。
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引用次数: 2
Ceramides in peripheral arterial plaque lead to endothelial cell dysfunction 外周动脉斑块中的神经酰胺导致内皮细胞功能障碍
Q3 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jvssci.2023.100181
Rodrigo Meade BS , Yang Chao MD, PhD , Nikolai Harroun MD , Chenglong Li MD , Shahab Hafezi MD , Fong-Fu Hsu PhD , Clay F. Semenkovich MD , Mohamed A. Zayed MD, PhD, MBA

Background

Peripheral arterial atheroprogression is increasingly prevalent, and is a risk factor for major limb amputations in individuals with risk factors such as diabetes. We previously demonstrated that bioactive lipids are significantly altered in arterial tissue of individuals with diabetes and advanced peripheral arterial disease.

Methods

Here we evaluated whether sphingolipid ceramide 18:1/16:0 (C16) is a cellular regulator in endothelial cells and peripheral tibial arterial tissue in individuals with diabetes.

Results

We observed that C16 is the single most elevated ceramide in peripheral arterial tissue from below the knee in individuals with diabetes (11% increase, P < .05). C16 content in tibial arterial tissue positively correlates with sphingomyelin (SPM) content in patients with and without diabetes (r2 = 0.5, P < .005; r2 = 0.17, P < .05; respectively). Tibial arteries of individuals with diabetes demonstrated no difference in CERS6 expression (encoding ceramide synthase 6; the predominate ceramide synthesis enzyme), but higher SMPD expression (encoding sphingomyelin phosphodiesterase that catalyzes ceramide synthesis from sphingomyelins; P < .05). SMPD4, but not SMPD2, was particularly elevated in maximally diseased (Max) tibial arterial segments (P < .05). In vitro, exogenous C16 caused endothelial cells (HUVECs) to have decreased proliferation (P < .03), increased apoptosis (P < .003), and decreased autophagy (P < .008). Selective knockdown of SMPD2 and SMPD4 decreased native production of C16 (P < .01 and P < .001, respectively), but only knockdown of SMPD4 rescued cellular proliferation (P < .005) following exogenous supplementation with C16.

Conclusions

Our findings suggest that C16 is a tissue biomarker for peripheral arterial disease severity in the setting of diabetes, and can impact endothelial cell viability and function.

Clinical relevance

Peripheral arterial disease and its end-stage manifestation known as chronic limb-threatening ischemia (CLTI) represent ongoing prevalent and intricate medical challenges. Individuals with diabetes have a heightened risk of developing CLTI and experiencing its complications, including wounds, ulcers, and major amputations. In the present study, we conducted a comprehensive examination of the molecular lipid composition within arterial segments from individuals with CLTI, and with and without diabetes. Our investigations unveiled a striking revelation: the sphingolipid ceramide 18:1/16:0 emerged as the predominant ceramide species that was significantly elevated in the peripheral arterial intima below the knee in patients with diabetes. Moreover, this heightened cera

背景:外周动脉粥样硬化进展越来越普遍,是糖尿病等危险因素导致截肢的危险因素。我们之前证明,生物活性脂质在糖尿病和晚期外周动脉疾病患者的动脉组织中显著改变。方法研究鞘脂神经酰胺18:1/16:0 (C16)是否在糖尿病患者的内皮细胞和胫外周动脉组织中起细胞调节作用。结果我们观察到C16是糖尿病患者膝以下外周动脉组织中升高最多的神经酰胺(增加11%,P <. 05)。糖尿病患者和非糖尿病患者胫骨动脉组织C16含量与鞘磷脂(SPM)含量呈正相关(r2 = 0.5, P <.005;r2 = 0.17, P <. 05;分别)。糖尿病患者胫骨动脉中CERS6的表达无差异(编码神经酰胺合成酶6;主要的神经酰胺合成酶),但较高的SMPD表达(编码鞘磷脂磷酸二酯酶,催化鞘磷脂合成神经酰胺;P & lt;. 05)。SMPD4,而不是SMPD2,在最大病变(Max)胫骨动脉段特别升高(P <. 05)。体外,外源性C16引起内皮细胞(HUVECs)增殖降低(P <.03),细胞凋亡增加(P <.003),自噬减少(P <.008)。选择性敲除SMPD2和SMPD4可降低C16的天然产量(P <.01和P <.001),但只有敲低SMPD4才能挽救细胞增殖(P <.005),外源性添加C16后。结论C16是糖尿病患者外周动脉疾病严重程度的组织生物标志物,可以影响内皮细胞的活力和功能。外周动脉疾病及其终末期表现为慢性肢体威胁性缺血(CLTI),是持续流行和复杂的医学挑战。糖尿病患者发生CLTI及其并发症的风险更高,包括伤口、溃疡和主要截肢。在本研究中,我们对CLTI患者、糖尿病患者和非糖尿病患者动脉段内的分子脂质组成进行了全面检查。我们的研究揭示了一个惊人的发现:鞘脂神经酰胺18:1/16:0成为糖尿病患者膝盖以下外周动脉内膜中显著升高的主要神经酰胺种类。此外,这种神经酰胺的存在与内皮细胞功能和活力的显著损害有关。此外,我们的研究还发现,在病变最严重的动脉段内,鞘磷脂磷酸二酯酶(负责催化鞘磷脂合成神经酰胺的酶)的表达同时升高。这些发现强调了神经酰胺及其生物合成酶在CLTI中的关键作用,为管理这一具有挑战性的疾病过程的潜在治疗途径提供了新的见解。
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引用次数: 0
A20 (tnfaip3) Knockdown Protects from Abdominal Aortic Aneurysms BY Limiting Extracellular Matrix Degradation and Maintaining Aortic Smooth Muscle Cell Mass A20(ttfaip3)基因敲除通过限制细胞外基质降解和维持主动脉平滑肌细胞质量来保护腹主动脉瘤
Q3 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jvssci.2023.100158
Tarek Aridi , John Gigioli , Nyah Patel , Jacqueline Wade , Phillip Brennan , Keyan Roshan , Cleide Angolano , Christiane Ferran
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引用次数: 0
Semiautomated Classification of Peripheral Artery Disease Lesion Composition From Multicontrast Magnetic Resonance Histology at 9..4 Tesla with A Two-Dimensional Convolutional Neural Network Variational AutoEncoder Algorithm 利用二维卷积神经网络变异自动编码器算法,从 9...4 特斯拉多对比磁共振组织学中对外周动脉疾病病变组成进行半自动分类
Q3 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jvssci.2023.100148
Judit Csore , Christof Karmonik , Alan B. Lumsden , Trisha L. Roy
{"title":"Semiautomated Classification of Peripheral Artery Disease Lesion Composition From Multicontrast Magnetic Resonance Histology at 9..4 Tesla with A Two-Dimensional Convolutional Neural Network Variational AutoEncoder Algorithm","authors":"Judit Csore ,&nbsp;Christof Karmonik ,&nbsp;Alan B. Lumsden ,&nbsp;Trisha L. Roy","doi":"10.1016/j.jvssci.2023.100148","DOIUrl":"https://doi.org/10.1016/j.jvssci.2023.100148","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350323000524/pdfft?md5=d7987633550e946ecf59849b1e56bd88&pid=1-s2.0-S2666350323000524-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139107262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Histone Demethylase JARID1c Regulates TH17 T-cells in Diabetic Wounds by Increasing IL-6 Expression in Plasmacytoid Dendritic Cells 组蛋白去甲基化酶 JARID1c 通过增加浆细胞树突状细胞中 IL-6 的表达调控糖尿病伤口中的 TH17 T 细胞
Q3 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jvssci.2023.100140
Chris Audu , William Melvin , Kevin Mangum , Amrita Joshi , Katherine A. Gallagher
{"title":"Histone Demethylase JARID1c Regulates TH17 T-cells in Diabetic Wounds by Increasing IL-6 Expression in Plasmacytoid Dendritic Cells","authors":"Chris Audu ,&nbsp;William Melvin ,&nbsp;Kevin Mangum ,&nbsp;Amrita Joshi ,&nbsp;Katherine A. Gallagher","doi":"10.1016/j.jvssci.2023.100140","DOIUrl":"https://doi.org/10.1016/j.jvssci.2023.100140","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350323000445/pdfft?md5=c03888a3cf6a3e61dcb41963d950fba0&pid=1-s2.0-S2666350323000445-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139108678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association Between SARS-COV-2 Infection And Abdominal Aortic Aneurysms SARS-COV-2 感染与腹主动脉瘤之间的关系
Q3 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jvssci.2023.100165
Baohui Xu, Toru Ikezoe, Jia Guo, Gang Li, Makoto Samura, Sihai Zhao, Ronald L. Dalman
{"title":"Association Between SARS-COV-2 Infection And Abdominal Aortic Aneurysms","authors":"Baohui Xu,&nbsp;Toru Ikezoe,&nbsp;Jia Guo,&nbsp;Gang Li,&nbsp;Makoto Samura,&nbsp;Sihai Zhao,&nbsp;Ronald L. Dalman","doi":"10.1016/j.jvssci.2023.100165","DOIUrl":"https://doi.org/10.1016/j.jvssci.2023.100165","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266635032300069X/pdfft?md5=0012fe43ca8ccf90b08a9b9bb398ea31&pid=1-s2.0-S266635032300069X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139108716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
E-selectin-overexpressing Mesenchymal Stem Cell-based Therapy Augments Cutaneous Wound Healing in Ischemic Limbs 基于 E 选择素表达的间充质干细胞疗法可促进缺血性肢体的皮肤伤口愈合
Q3 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jvssci.2023.100174
Carlos T. Huerta , Yulexi Ortiz , Yan Li , Antoine Ribieras , Francesca Voza , Nga Le , Zhao-Jun Liu , Omaida Caridad Velazquez
{"title":"E-selectin-overexpressing Mesenchymal Stem Cell-based Therapy Augments Cutaneous Wound Healing in Ischemic Limbs","authors":"Carlos T. Huerta ,&nbsp;Yulexi Ortiz ,&nbsp;Yan Li ,&nbsp;Antoine Ribieras ,&nbsp;Francesca Voza ,&nbsp;Nga Le ,&nbsp;Zhao-Jun Liu ,&nbsp;Omaida Caridad Velazquez","doi":"10.1016/j.jvssci.2023.100174","DOIUrl":"https://doi.org/10.1016/j.jvssci.2023.100174","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350323000780/pdfft?md5=1dcfa4733b260161b2a6381a930d2a62&pid=1-s2.0-S2666350323000780-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139108826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Thrombosis in the pathogenesis of abdominal aortic aneurysm 血栓形成在腹主动脉瘤发病机制中的作用
Q3 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jvssci.2023.100106
Jack Bontekoe MD , Jon Matsumura MD , Bo Liu PhD

Background

Abdominal aortic aneurysms (AAAs) are a relatively common vascular pathology of the elderly with high morbidity potential. Irreversible degeneration of the aortic wall leads to lethal rupture if left untreated. Nearly all AAAs contain intraluminal thrombus (ILT) to a varying degree, yet the mechanisms explaining how thrombosis is disturbed in AAA are relatively unknown. This review examined the thrombotic complications associated with AAA, the impact of thrombosis on AAA surgical outcomes and AAA pathogenesis, and the use of antithrombotic therapy in the management of this disease.

Methods

A literature search of the PubMed database was conducted using relevant keywords related to thrombosis and AAAs.

Results

Thrombotic complications are relatively infrequent in AAA yet carry significant morbidity risks. The ILT can impact endovascular aneurysm repair by limiting anatomic suitability and influence the risk of endoleaks. Many of the pathologic mechanisms involved in AAA development, including hemodynamics, inflammation, oxidative stress, and aortic wall remodeling, contain pathways that interact with thrombosis. Conversely, the ILT can also be a source of biochemical stress and exacerbate these aneurysmal processes. In animal AAA models, antithrombotic therapies have shown favorable results in preventing and stabilizing AAA. Antiplatelet agents may be beneficial for reducing risks of major adverse cardiovascular events in AAA patients; however, neither antiplatelet nor anticoagulation is currently used solely for the management of AAA.

Conclusions

Thrombosis and ILT may have detrimental effects on AAA growth, rupture risk, and patient outcomes, yet there is limited understanding of the pathologic thrombotic mechanisms in aneurysmal disease at the molecular level. Preventing ILT using platelet and coagulation inhibitors may be a reasonable theoretical target for aneurysm progression and stability; however, the practical benefits of current antithrombotic therapies in AAA are unclear. Further research is needed to demonstrate the extent to which thrombosis impacts AAA pathogenesis and to develop novel pharmacologic strategies for the medical management of this disease.

背景腹主动脉瘤(AAAs)是老年人较为常见的血管性病变,具有较高的发病率。不可逆的主动脉壁退化如果不及时治疗会导致致命的破裂。几乎所有的AAA都不同程度地含有腔内血栓(ILT),但血栓形成在AAA中受到干扰的机制相对未知。本文综述了与AAA相关的血栓性并发症、血栓形成对AAA手术结果的影响、AAA发病机制以及抗血栓治疗在该疾病治疗中的应用。方法采用血栓形成、AAAs相关关键词检索PubMed数据库的文献。结果血栓性并发症在AAA患者中相对少见,但有显著的发病率风险。ILT可以通过限制解剖适应性和影响血管内泄漏的风险来影响血管内动脉瘤的修复。AAA发展的许多病理机制,包括血流动力学、炎症、氧化应激和主动脉壁重塑,都包含与血栓形成相互作用的途径。相反,ILT也可能是生化应激的来源,并加剧这些动脉瘤的过程。在动物AAA模型中,抗血栓治疗在预防和稳定AAA方面显示出良好的效果。抗血小板药物可能有助于降低AAA患者主要不良心血管事件的风险;结论血栓形成和ILT可能对动脉瘤生长、破裂风险和患者预后有不利影响,但在分子水平上对动脉瘤疾病的病理性血栓形成机制的了解有限。使用血小板和凝血抑制剂预防ILT可能是动脉瘤进展和稳定的合理理论目标;然而,目前抗血栓治疗在AAA中的实际益处尚不清楚。需要进一步的研究来证明血栓形成对AAA发病机制的影响程度,并为这种疾病的医学管理开发新的药理学策略。
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引用次数: 0
Mechanisms and efficacy of metformin-mediated suppression of established experimental abdominal aortic aneurysms 二甲双胍介导的实验性腹主动脉瘤抑制的机制和疗效
Q3 Medicine Pub Date : 2023-01-01 DOI: 10.1016/j.jvssci.2023.100102
Baohui Xu MD, PhD , Gang Li MD, PhD , Yankui Li MD, PhD , Hongping Deng MD, PhD , Anna Cabot BS , Jia Guo MD, PhD , Makoto Samura MD, PhD , Xiaoya Zheng MD, PhD , Tiffany Chen BS , Sihai Zhao MD, PhD , Naoki Fujimura MD, PhD , Ronald L. Dalman MD

Objective

Metformin treatment attenuates experimental abdominal aortic aneurysm (AAA) formation, as well as reduces clinical AAA diameter enlargement in patients with diabetes. The mechanisms of metformin-mediated aneurysm suppression, and its efficacy in suppressing established experimental aneurysms, remain uncertain.

Methods

Experimental AAAs were created in male C57BL/6J mice via intra-aortic infusion of porcine pancreatic elastase. Metformin alone (250 mg/kg), or metformin combined with the 5′ AMP-activated protein kinase (AMPK) antagonist Compound C (10 mg/kg), were administered to respective mouse cohorts daily beginning 4 days following AAA induction. Further AAA cohorts received either the AMPK agonist AICA riboside (500 mg/kg) as positive, or vehicle (saline) as negative, controls. AAA progression in all groups was assessed via serial in vivo ultrasonography and histopathology at sacrifice. Cytokine-producing T cells and myeloid cellularity were determined by flow cytometric analyses.

Results

Metformin limited established experimental AAA progression at 3 (−85%) and 10 (−68%) days following treatment initiation compared with saline control. Concurrent Compound C treatment reduced this effect by approximately 50%. In metformin-treated mice, reduced AAA progression was associated with relative elastin preservation, smooth muscle cell preservation, and reduced mural leukocyte infiltration and neoangiogenesis compared with vehicle control group. Metformin also resulted in reduced interferon-γ-, but not interleukin-10 or -17, producing splenic T cells in aneurysmal mice. Additionally, metformin therapy increased circulating and splenic inflammatory monocytes (CD11b+Ly-6Chigh), but not neutrophils (CD11b+Ly-6G+), with no effect on respective bone marrow cell populations.

Conclusions

Metformin treatment suppresses existing experimental AAA progression in part via AMPK agonist activity, limiting interferon-γ-producing T cell differentiation while enhancing circulating and splenic inflammatory monocyte retention.

目的:甲双胍治疗糖尿病患者实验性腹主动脉瘤(AAA)的形成,降低临床AAA直径增大。二甲双胍介导的动脉瘤抑制机制及其在抑制已建立的实验性动脉瘤中的有效性仍不确定。方法采用猪胰弹性酶主动脉内灌注法,在雄性C57BL/6J小鼠腹腔内制造实验性AAAs。在AAA诱导后的第4天,每天分别给药二甲双胍单独(250 mg/kg),或二甲双胍联合5 ' amp活化的蛋白激酶(AMPK)拮抗剂化合物C (10 mg/kg)。进一步的AAA队列接受AMPK激动剂AICA核苷(500 mg/kg)作为阳性,或载体(生理盐水)作为阴性对照。在牺牲时,通过连续的体内超声检查和组织病理学来评估所有组的AAA进展。流式细胞术检测细胞因子生成T细胞和髓细胞结构。结果与生理盐水对照组相比,二甲双胍在治疗开始后3天(−85%)和10天(−68%)限制了已建立的实验性AAA进展。同时使用复方C治疗可使这种效果降低约50%。在二甲双胍治疗的小鼠中,与对照组相比,AAA进展的减少与相对弹性蛋白保存、平滑肌细胞保存、壁白细胞浸润和新生血管生成的减少有关。二甲双胍还导致动脉瘤小鼠脾T细胞产生的干扰素-γ-减少,但白细胞介素-10或-17没有减少。此外,二甲双胍治疗增加了循环和脾炎性单核细胞(CD11b+ ly - 6高),但没有增加中性粒细胞(CD11b+Ly-6G+),对各自的骨髓细胞群没有影响。结论二甲双胍治疗抑制实验性AAA进展,部分是通过AMPK激动剂活性,限制产生干扰素γ的T细胞分化,同时增强循环和脾炎性单核细胞保留。
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引用次数: 2
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JVS-vascular science
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