JVS-vascular science最新文献

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Cystathionine-γ-lyase overexpression modulates oxidized nicotinamide adenine dinucleotide biosynthesis and enhances neovascularization 半胱硫氨酸-γ-裂解酶过表达调节氧化烟酰胺腺嘌呤二核苷酸生物合成,促进新生血管形成
JVS-vascular science Pub Date : 2023-01-01 DOI: 10.1016/j.jvssci.2022.11.003
Kevin Kiesworo MS , Michael R. MacArthur PhD , Peter Kip MD, PhD , Thomas Agius MS , Diane Macabrey MS , Martine Lambelet BS , Lauriane Hamard PhD , C.-Keith Ozaki MD , James R. Mitchell PhD , Sébastien Déglise MD , Sarah J. Mitchell PhD , Florent Allagnat PhD , Alban Longchamp MD, PhD
{"title":"Cystathionine-γ-lyase overexpression modulates oxidized nicotinamide adenine dinucleotide biosynthesis and enhances neovascularization","authors":"Kevin Kiesworo MS ,&nbsp;Michael R. MacArthur PhD ,&nbsp;Peter Kip MD, PhD ,&nbsp;Thomas Agius MS ,&nbsp;Diane Macabrey MS ,&nbsp;Martine Lambelet BS ,&nbsp;Lauriane Hamard PhD ,&nbsp;C.-Keith Ozaki MD ,&nbsp;James R. Mitchell PhD ,&nbsp;Sébastien Déglise MD ,&nbsp;Sarah J. Mitchell PhD ,&nbsp;Florent Allagnat PhD ,&nbsp;Alban Longchamp MD, PhD","doi":"10.1016/j.jvssci.2022.11.003","DOIUrl":"10.1016/j.jvssci.2022.11.003","url":null,"abstract":"<div><h3>Objective</h3><p>Hydrogen sulfide is a proangiogenic gas produced primarily by the transsulfuration enzyme cystathionine-γ-lyase (CGL). CGL-dependent hydrogen sulfide production is required for neovascularization in models of peripheral arterial disease. However, the benefits of increasing endogenous CGL and its mechanism of action have not yet been elucidated.</p></div><div><h3>Methods</h3><p>Male whole body CGL-overexpressing transgenic (CGL<sup>Tg</sup>) mice and wild-type (WT) littermates (C57BL/6J) were subjected to the hindlimb ischemia model (age, 10-12 weeks). Functional recovery was assessed via the treadmill exercise endurance test. Leg perfusion was measured by laser Doppler imaging and vascular endothelial-cadherin immunostaining. To examine the angiogenic potential, aortic ring sprouting assay and postnatal mouse retinal vasculature development studies were performed. Finally, comparative metabolomics analysis, oxidized/reduced nicotinamide adenine dinucleotide (NAD<sup>+</sup>/NADH) analysis, and quantitative real-time polymerase chain reaction were performed on CGL<sup>WT</sup> and CGL<sup>Tg</sup> gastrocnemius muscle.</p></div><div><h3>Results</h3><p>The restoration of blood flow occurred more rapidly in CGL<sup>Tg</sup> mice. Compared with the CGL<sup>WT</sup> mice, the median ± standard deviation running distance and time were increased for the CGL<sup>Tg</sup> mice after femoral artery ligation (159 ± 53 m vs 291 ± 74 m [<em>P</em> &lt; .005] and 17 ± 4 minutes vs 27 ± 5 minutes [<em>P</em> &lt; .05], respectively). Consistently, in the CGL<sup>Tg</sup> ischemic gastrocnemius muscle, the capillary density was increased fourfold (0.05 ± 0.02 vs 0.20 ± 0.12; <em>P</em> &lt; .005). Ex vivo, the endothelial cell (EC) sprouting length was increased in aorta isolated from CGL<sup>Tg</sup> mice, especially when cultured in VEGFA (vascular endothelial growth factor A)-only media (63 ± 2 pixels vs 146 ± 52 pixels; <em>P</em> &lt; .05). Metabolomics analysis demonstrated a higher level of niacinamide, a precursor of NAD<sup>+</sup>/NADH in the muscle of CGL<sup>Tg</sup> mice (61.4 × 10<sup>6</sup> ± 5.9 × 10<sup>6</sup> vs 72.4 ± 7.7 × 10<sup>6</sup> area under the curve; <em>P</em> &lt; .05). Similarly, the NAD<sup>+</sup> salvage pathway gene expression was increased in CGL<sup>Tg</sup> gastrocnemius muscle. Finally, CGL overexpression or supplementation with the NAD<sup>+</sup> precursor nicotinamide mononucleotide improved EC migration in vitro (wound closure: control, 35% ± 9%; CGL, 55% ± 11%; nicotinamide mononucleotide, 42% ± 13%; <em>P</em> &lt; .05).</p></div><div><h3>Conclusions</h3><p>Our results have demonstrated that CGL overexpression improves the neovascularization of skeletal muscle on hindlimb ischemia. These effects correlated with changes in the NAD pathway, which improved EC migration.</p></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"4 ","pages":"Article 100095"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9369038","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: 2
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
JVS-vascular science 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
{"title":"Degradation phenomena on last generations of polyethylene terephthalate knitted vascular prostheses","authors":"Arielle Bellissard MD ,&nbsp;Nabil Chakfe MD, PhD ,&nbsp;Salomé Kuntz MD, MSc ,&nbsp;Delphine Dion MSc ,&nbsp;Lory Schmitt ,&nbsp;Frédéric Heim PhD ,&nbsp;Anne Lejay MD, PhD","doi":"10.1016/j.jvssci.2023.01.001","DOIUrl":"10.1016/j.jvssci.2023.01.001","url":null,"abstract":"<div><h3>Objectives</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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.</p><p>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.</p></div><div><h3>Conclusions</h3><p>New-generation PET VG degradation seems to result from both anatomic constraints and intrinsic textile structure phenomena.</p></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"4 ","pages":"Article 100097"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/75/25/main.PMC10165261.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9458181","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
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
JVS-vascular science 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
{"title":"Machine learning analysis of confounding variables of a convolutional neural network specific for abdominal aortic aneurysms","authors":"Roger T. Tomihama MD ,&nbsp;Justin R. Camara MD ,&nbsp;Sharon C. Kiang MD","doi":"10.1016/j.jvssci.2022.11.004","DOIUrl":"10.1016/j.jvssci.2022.11.004","url":null,"abstract":"<div><h3>Objective</h3><p>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).</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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 &lt;3.3 cm, 32% (11/34) for aneurysms 3.3 to 5 cm, and 20% (7/34) for aneurysms &gt;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%, <em>P</em> &lt; .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.</p></div><div><h3>Conclusions</h3><p>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 (&lt;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.</p></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"4 ","pages":"Article 100096"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a6/a7/main.PMC10245322.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9607150","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: 2
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
JVS-vascular science 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
{"title":"A20 (tnfaip3) Knockdown Protects from Abdominal Aortic Aneurysms BY Limiting Extracellular Matrix Degradation and Maintaining Aortic Smooth Muscle Cell Mass","authors":"Tarek Aridi ,&nbsp;John Gigioli ,&nbsp;Nyah Patel ,&nbsp;Jacqueline Wade ,&nbsp;Phillip Brennan ,&nbsp;Keyan Roshan ,&nbsp;Cleide Angolano ,&nbsp;Christiane Ferran","doi":"10.1016/j.jvssci.2023.100158","DOIUrl":"https://doi.org/10.1016/j.jvssci.2023.100158","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"4 ","pages":"Article 100158"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350323000627/pdfft?md5=049731588b10a4eeee22b2826a8896fc&pid=1-s2.0-S2666350323000627-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139107180","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
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
JVS-vascular science 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":"4 ","pages":"Article 100148"},"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
JVS-vascular science 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":"4 ","pages":"Article 100140"},"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
JVS-vascular science 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":"4 ","pages":"Article 100165"},"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
JVS-vascular science 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":"4 ","pages":"Article 100174"},"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
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
JVS-vascular science 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
{"title":"Ceramides in peripheral arterial plaque lead to endothelial cell dysfunction","authors":"Rodrigo Meade BS ,&nbsp;Yang Chao MD, PhD ,&nbsp;Nikolai Harroun MD ,&nbsp;Chenglong Li MD ,&nbsp;Shahab Hafezi MD ,&nbsp;Fong-Fu Hsu PhD ,&nbsp;Clay F. Semenkovich MD ,&nbsp;Mohamed A. Zayed MD, PhD, MBA","doi":"10.1016/j.jvssci.2023.100181","DOIUrl":"10.1016/j.jvssci.2023.100181","url":null,"abstract":"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>We observed that C16 is the single most elevated ceramide in peripheral arterial tissue from below the knee in individuals with diabetes (11% increase, <em>P</em> &lt; .05). C16 content in tibial arterial tissue positively correlates with sphingomyelin (SPM) content in patients with and without diabetes (r<sup>2</sup> = 0.5, <em>P</em> &lt; .005; r<sup>2</sup> = 0.17, <em>P</em> &lt; .05; respectively). Tibial arteries of individuals with diabetes demonstrated no difference in <em>CERS6</em> expression (encoding ceramide synthase 6; the predominate ceramide synthesis enzyme), but higher <em>SMPD</em> expression (encoding sphingomyelin phosphodiesterase that catalyzes ceramide synthesis from sphingomyelins; <em>P</em> &lt; .05). <em>SMPD4,</em> but not <em>SMPD2</em>, was particularly elevated in maximally diseased (Max) tibial arterial segments (<em>P</em> &lt; .05). In vitro, exogenous C16 caused endothelial cells (HUVECs) to have decreased proliferation (<em>P</em> &lt; .03), increased apoptosis (<em>P</em> &lt; .003), and decreased autophagy (<em>P</em> &lt; .008). Selective knockdown of <em>SMPD2</em> and <em>SMPD4</em> decreased native production of C16 (<em>P</em> &lt; .01 and <em>P</em> &lt; .001, respectively), but only knockdown of SMPD4 rescued cellular proliferation (<em>P</em> &lt; .005) following exogenous supplementation with C16.</p></div><div><h3>Conclusions</h3><p>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.</p></div><div><h3>Clinical relevance</h3><p>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","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"4 ","pages":"Article 100181"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350323000858/pdfft?md5=3d3bd95adba87869a0086af3cb8d6207&pid=1-s2.0-S2666350323000858-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135670049","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
JVS-vascular science Pub Date : 2023-01-01 DOI: 10.1016/j.jvssci.2023.100106
Jack Bontekoe MD , Jon Matsumura MD , Bo Liu PhD
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