Pub Date : 2024-01-01DOI: 10.1016/j.jvssci.2024.100215
Gabriel Cruz-González MD , James F. Meschia MD , Benjamin J. Madden BSc , Mercedes Prudencio PhD , Camilo A. Polania-Sandoval MD , Janelle Hartwell BS , Eniola Oyefeso BS , Ranya Benchaaboune , Tara Brigham MLIS , Sukhwinder J.S. Sandhu MD , Cristine Charlesworth PhD, MS , Ganesh P. Pujari MD , Leonard Petrucelli PhD , Akhilesh Pandey MD, PhD , Young Erben MD
Objective
We sought to identify differentially expressed proteins in serum, plasma, and plaque samples of patients with carotid atherosclerotic lesions.
Methods
We performed a systematic review of the proteomic profile of serum, plasma, and plaque samples of patients with carotid artery disease. We included full-length peer-reviewed studies of adult humans and reported them using PRISMA guidelines. The quality of the design and content of the articles included in the review was assessed using the Newcastle-Ottawa scale.
Results
We included six peer-reviewed articles reporting protein expression in serum, plasma, or plaque samples from patients with carotid atherosclerosis. Three were single-center cross-sectional studies, two were single-center case-control studies, and one was a single-center cohort study. Thirty-six proteins were found to be expressed differentially when comparing samples from healthy subjects and individuals with diseased carotid vessels and between patients with symptomatic and asymptomatic carotid artery atherosclerotic lesions. Some of these were shown to be related to inflammatory or anti-inflammatory pathways in atherogenesis. CD5L and S100A12 were both found to be upregulated in patients with unstable plaque, the former owing to its anti-inflammatory properties and the latter for its pro-oxidant effects in atherosclerosis. ACTB is involved in cellular structure and integrity and was found to be downregulated in patients with ruptured carotid plaques.
Conclusions
Atherosclerotic carotid disease places the patient at increased risk of ischemic neurological events. Proteomics may help to understand their pathophysiological processes and can identify differential protein expression in blood samples from healthy subjects and patients with carotid artery plaques. This patient-centered approach will allow for the timely identification of individuals at higher risk of experiencing stroke.
{"title":"Recent advances in proteomic analysis to study carotid artery plaques","authors":"Gabriel Cruz-González MD , James F. Meschia MD , Benjamin J. Madden BSc , Mercedes Prudencio PhD , Camilo A. Polania-Sandoval MD , Janelle Hartwell BS , Eniola Oyefeso BS , Ranya Benchaaboune , Tara Brigham MLIS , Sukhwinder J.S. Sandhu MD , Cristine Charlesworth PhD, MS , Ganesh P. Pujari MD , Leonard Petrucelli PhD , Akhilesh Pandey MD, PhD , Young Erben MD","doi":"10.1016/j.jvssci.2024.100215","DOIUrl":"10.1016/j.jvssci.2024.100215","url":null,"abstract":"<div><h3>Objective</h3><p>We sought to identify differentially expressed proteins in serum, plasma, and plaque samples of patients with carotid atherosclerotic lesions.</p></div><div><h3>Methods</h3><p>We performed a systematic review of the proteomic profile of serum, plasma, and plaque samples of patients with carotid artery disease. We included full-length peer-reviewed studies of adult humans and reported them using PRISMA guidelines. The quality of the design and content of the articles included in the review was assessed using the Newcastle-Ottawa scale.</p></div><div><h3>Results</h3><p>We included six peer-reviewed articles reporting protein expression in serum, plasma, or plaque samples from patients with carotid atherosclerosis. Three were single-center cross-sectional studies, two were single-center case-control studies, and one was a single-center cohort study. Thirty-six proteins were found to be expressed differentially when comparing samples from healthy subjects and individuals with diseased carotid vessels and between patients with symptomatic and asymptomatic carotid artery atherosclerotic lesions. Some of these were shown to be related to inflammatory or anti-inflammatory pathways in atherogenesis. CD5L and S100A12 were both found to be upregulated in patients with unstable plaque, the former owing to its anti-inflammatory properties and the latter for its pro-oxidant effects in atherosclerosis. ACTB is involved in cellular structure and integrity and was found to be downregulated in patients with ruptured carotid plaques.</p></div><div><h3>Conclusions</h3><p>Atherosclerotic carotid disease places the patient at increased risk of ischemic neurological events. Proteomics may help to understand their pathophysiological processes and can identify differential protein expression in blood samples from healthy subjects and patients with carotid artery plaques. This patient-centered approach will allow for the timely identification of individuals at higher risk of experiencing stroke.</p></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"5 ","pages":"Article 100215"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350324000269/pdfft?md5=0724ce0ddb26f766af2d098433cbd988&pid=1-s2.0-S2666350324000269-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270515","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}
Pub Date : 2024-01-01DOI: 10.1016/j.jvssci.2024.100210
Thijs J. Sluiter MSc , Lucinda Cruddas MBBS , Federica Ninno MRes , Thomas Schmitz-Rixen MD, PhD , Janice Tsui MD, FRCS , Margreet R. de Vries PhD
The Basic Vascular Science (BVS) meeting was set up to provide a forum for researchers and clinicians in the field to exchange knowledge and ideas and to foster cross-disciplinary collaborations. The BVS 2024 meeting was held in Berlin. Attended by vascular surgeons and physicians, interventional radiologists, basic science researchers, and engineers, the meeting continues to successfully attract both early career researchers and established clinician-scientists. Here, we report on the scientific sessions encompassing keynote lectures and oral presentations.
{"title":"Basic Vascular Science 2024 Meeting","authors":"Thijs J. Sluiter MSc , Lucinda Cruddas MBBS , Federica Ninno MRes , Thomas Schmitz-Rixen MD, PhD , Janice Tsui MD, FRCS , Margreet R. de Vries PhD","doi":"10.1016/j.jvssci.2024.100210","DOIUrl":"10.1016/j.jvssci.2024.100210","url":null,"abstract":"<div><p>The Basic Vascular Science (BVS) meeting was set up to provide a forum for researchers and clinicians in the field to exchange knowledge and ideas and to foster cross-disciplinary collaborations. The BVS 2024 meeting was held in Berlin. Attended by vascular surgeons and physicians, interventional radiologists, basic science researchers, and engineers, the meeting continues to successfully attract both early career researchers and established clinician-scientists. Here, we report on the scientific sessions encompassing keynote lectures and oral presentations.</p></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"5 ","pages":"Article 100210"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266635032400021X/pdfft?md5=a901ea037bdb368d4a77d022a15f8357&pid=1-s2.0-S266635032400021X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141276653","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}
Pub Date : 2024-01-01DOI: 10.1016/j.jvssci.2024.100198
Dakota W. Gonring BA , Zachary R. Zottola BS , Adnan A. Hirad MD, PhD , Ronald Lakony BS , Michael S. Richards PhD , Grayson Pitcher MD , Michael C. Stoner MD , Doran S. Mix MD
Objective
Strain has become a viable index for evaluating abdominal aortic aneurysm stability after endovascular aneurysm repair (EVAR). In addition, literature has shown that healthy aortic tissue requires a degree of strain to maintain homeostasis. This has led to the hypothesis that too much strain reduction conferred by a high degree of graft oversizing is detrimental to the aneurysm neck in the seal zone of abdominal aortic aneurysms after EVAR. We investigated this in a laboratory experiment by examining the effects that graft oversizing has on the pressure-normalized strain (/pulse pressure [PP]) reduction using four different infrarenal EVAR endografts and our ultrasound elastography technique. Approximate graft oversizing percentages were 20% (30 mm phantom-graft combinations), 30% (28 mm phantom-graft combinations), and 50% (24 mm phantom-graft combinations).
Methods
Axisymmetric, 10% by mass polyvinyl alcohol phantoms were connected to a flow simulator. Ultrasound elastography was performed before and after implantation with the four different endografts: (1) 36 mm polyester/stainless steel, (2) 36 mm polyester/electropolished nitinol, (3) 35 mm polytetrafluoroethylene (PTFE)/nitinol, and (4) 36 mm nitinol/polyester/platinum-iridium. Five ultrasound cine loops were taken of each phantom-graft combination. They were analyzed over two different cardiac cycles (end-diastole to end-diastole), yielding a total of 10 maximum mean principal strain () values. was divided by pulse pressure to yield pressure-normalized strain (/PP). An analysis of variance was performed for graft comparisons. We calculated the average percent /PP reduction by manufacturer and percent oversizing. These values were used for linear regression analysis.
Results
Results from one-way analysis of variance showed a significant difference in /PP between the empty phantom condition and all oversizing conditions for all graft manufacturers (F(3, 56) = 106.7 [graft A], 132.7 [graft B], 106.5 [graft C], 105.7 [graft D], P < .0001 for grafts A-D). There was a significant difference when comparing the 50% condition with the 30% and 20% conditions across all manufacturers by post hoc a
{"title":"Ultrasound elastography to quantify average percent pressure-normalized strain reduction associated with different aortic endografts in 3D-printed hydrogel phantoms","authors":"Dakota W. Gonring BA , Zachary R. Zottola BS , Adnan A. Hirad MD, PhD , Ronald Lakony BS , Michael S. Richards PhD , Grayson Pitcher MD , Michael C. Stoner MD , Doran S. Mix MD","doi":"10.1016/j.jvssci.2024.100198","DOIUrl":"10.1016/j.jvssci.2024.100198","url":null,"abstract":"<div><h3>Objective</h3><p>Strain has become a viable index for evaluating abdominal aortic aneurysm stability after endovascular aneurysm repair (EVAR). In addition, literature has shown that healthy aortic tissue requires a degree of strain to maintain homeostasis. This has led to the hypothesis that too much strain reduction conferred by a high degree of graft oversizing is detrimental to the aneurysm neck in the seal zone of abdominal aortic aneurysms after EVAR. We investigated this in a laboratory experiment by examining the effects that graft oversizing has on the pressure-normalized strain (<span><math><mrow><mover><msub><mi>ε</mi><mrow><mi>ρ</mi><mo>+</mo></mrow></msub><mo>¯</mo></mover></mrow></math></span>/pulse pressure [PP]) reduction using four different infrarenal EVAR endografts and our ultrasound elastography technique. Approximate graft oversizing percentages were 20% (30 mm phantom-graft combinations), 30% (28 mm phantom-graft combinations), and 50% (24 mm phantom-graft combinations).</p></div><div><h3>Methods</h3><p>Axisymmetric, 10% by mass polyvinyl alcohol phantoms were connected to a flow simulator. Ultrasound elastography was performed before and after implantation with the four different endografts: (1) 36 mm polyester/stainless steel, (2) 36 mm polyester/electropolished nitinol, (3) 35 mm polytetrafluoroethylene (PTFE)/nitinol, and (4) 36 mm nitinol/polyester/platinum-iridium. Five ultrasound cine loops were taken of each phantom-graft combination. They were analyzed over two different cardiac cycles (end-diastole to end-diastole), yielding a total of 10 maximum mean principal strain (<span><math><mrow><mover><msub><mi>ε</mi><mrow><mi>ρ</mi><mo>+</mo></mrow></msub><mo>¯</mo></mover></mrow></math></span>) values. <span><math><mrow><mover><msub><mi>ε</mi><mrow><mi>ρ</mi><mo>+</mo></mrow></msub><mo>¯</mo></mover></mrow></math></span> was divided by pulse pressure to yield pressure-normalized strain (<span><math><mrow><mover><msub><mi>ε</mi><mrow><mi>ρ</mi><mo>+</mo></mrow></msub><mo>¯</mo></mover></mrow></math></span>/PP). An analysis of variance was performed for graft comparisons. We calculated the average percent <span><math><mrow><mover><msub><mi>ε</mi><mrow><mi>ρ</mi><mo>+</mo></mrow></msub><mo>¯</mo></mover></mrow></math></span>/PP reduction by manufacturer and percent oversizing. These values were used for linear regression analysis.</p></div><div><h3>Results</h3><p>Results from one-way analysis of variance showed a significant difference in <span><math><mrow><mover><msub><mi>ε</mi><mrow><mi>ρ</mi><mo>+</mo></mrow></msub><mo>¯</mo></mover></mrow></math></span>/PP between the empty phantom condition and all oversizing conditions for all graft manufacturers (<em>F</em>(3, 56) = 106.7 [graft A], 132.7 [graft B], 106.5 [graft C], 105.7 [graft D], <em>P</em> < .0001 for grafts A-D). There was a significant difference when comparing the 50% condition with the 30% and 20% conditions across all manufacturers by post hoc a","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"5 ","pages":"Article 100198"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350324000099/pdfft?md5=174462f0b3289da4a0f6e8331d8e0f44&pid=1-s2.0-S2666350324000099-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140270596","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}
Pub Date : 2024-01-01DOI: 10.1016/j.jvssci.2024.100192
Xiao Luo PhD , Fattah Muhammad Tahabi BS , Dave M. Rollins RVT , Alan P. Sawchuk MD
Objective
Routine surveillance with duplex ultrasound (DUS) examination is recommended after femoral-popliteal and femoral-tibial-pedal vein bypass grafts with various intervals postoperatively. The presently used methodology to analyze bypass graft DUS examination does not use all the available data and has been shown to have a significant rate for missing impending bypass graft failure. The objective of this research is to investigate recurrent neural networks (RNNs) to predict future bypass graft occlusion or stenosis.
Methods
This study includes DUS examinations of 663 patients who had bypass graft operations done between January 2009 and June 2022. Only examinations without missing values were included. We developed two RNNs (a bidirectional long short-term memory unit and a bidirectional gated recurrent unit) to predict bypass graft occlusion and stenosis based on peak systolic velocities collected in the 2 to 5 previous DUS examinations. We excluded the examinations with missing values and split our data into training and test sets. Then, we applied 10-fold cross-validation on training to optimize the hyperparameters and compared models using the test data.
Results
The bidirectional long short-term memory unit model can gain an overall sensitivity of 0.939, specificity of 0.963, and area under the curve of 0.950 on the prediction of bypass graft occlusion, and an overall sensitivity of 0.915, specificity of 0.909, and area under the curve of 0.912 predicting the development of a future critical stenosis. The results on different bypass types show that the system performs differently on different types. The results on subcohorts based on gender, smoking status, and comorbidities show that the performance on current smokers is lower than the never smoker.
Conclusions
We found that RNNs can gain good sensitivity, specificity, and accuracy for the detection of impending bypass graft occlusion or the future development of a critical bypass graft stenosis using all the available peak systolic velocity data in the present and previous bypass graft DUS examinations. Integrating clinical data, including demographics, social determinants, medication, and other risk factors, together with the DUS examination may result in further improvements.
Clinical Relevance
Detecting bypass graft failure before it occurs is important clinically to prevent amputations, salvage limbs, and save lives. Current methods evaluating screening duplex ultrasound examinations have a significant failure rate for detecting a bypass graft at risk for failure. Artificial intelligence using recurrent neural networks has the potential to improve the detection of at-risk bypass graft before they fail. Additionally, artificial intelligence is in the news and is being applied to many fields. Vascular surgeons need to know its potential to improve vascular outcomes.
目的建议在股-腘静脉和股-胫-腓静脉旁路移植术后的不同时间间隔内使用双工超声（DUS）进行常规监测。目前使用的旁路移植术 DUS 检查分析方法并未使用所有可用数据，而且已被证明有很大可能遗漏即将发生的旁路移植术失败。本研究的目的是研究用递归神经网络（RNN）来预测未来旁路移植管闭塞或狭窄的情况。方法本研究包括对 2009 年 1 月至 2022 年 6 月间接受旁路移植手术的 663 名患者进行的 DUS 检查。仅纳入了无缺失值的检查。我们开发了两个 RNN（双向长短期记忆单元和双向门控复发单元），根据之前 2 到 5 次 DUS 检查中收集的收缩速度峰值预测旁路移植闭塞和狭窄。我们排除了有缺失值的检查，并将数据分成训练集和测试集。结果双向长短期记忆单元模型在预测旁路移植闭塞方面的总体灵敏度为 0.939，特异性为 0.963，曲线下面积为 0.950；在预测未来发生临界狭窄方面的总体灵敏度为 0.915，特异性为 0.909，曲线下面积为 0.912。不同分流类型的结果表明，该系统对不同类型的分流有不同的表现。基于性别、吸烟状况和合并症的亚群结果显示，当前吸烟者的表现低于从未吸烟者。结论我们发现，RNN 可以利用当前和之前旁路移植 DUS 检查中所有可用的收缩压峰值速度数据，获得良好的灵敏度、特异性和准确性，用于检测即将发生的旁路移植闭塞或未来发展为临界旁路移植狭窄。将临床数据（包括人口统计学、社会决定因素、药物和其他风险因素）与 DUS 检查结合起来可能会带来进一步的改进。临床意义在旁路移植失败发生之前进行检测对于防止截肢、抢救肢体和挽救生命具有重要的临床意义。目前评估筛查双相超声检查的方法在检测有失效风险的旁路移植方面有很大的失败率。使用递归神经网络的人工智能有可能在搭桥术失败前提高对高风险搭桥术的检测率。此外，人工智能已成为新闻，并被应用于许多领域。血管外科医生需要了解人工智能在改善血管治疗效果方面的潜力。
{"title":"Predicting future occlusion or stenosis of lower extremity bypass grafts using artificial intelligence to simultaneously analyze all flow velocities collected in current and previous ultrasound examinations","authors":"Xiao Luo PhD , Fattah Muhammad Tahabi BS , Dave M. Rollins RVT , Alan P. Sawchuk MD","doi":"10.1016/j.jvssci.2024.100192","DOIUrl":"10.1016/j.jvssci.2024.100192","url":null,"abstract":"<div><h3>Objective</h3><p>Routine surveillance with duplex ultrasound (DUS) examination is recommended after femoral-popliteal and femoral-tibial-pedal vein bypass grafts with various intervals postoperatively. The presently used methodology to analyze bypass graft DUS examination does not use all the available data and has been shown to have a significant rate for missing impending bypass graft failure. The objective of this research is to investigate recurrent neural networks (RNNs) to predict future bypass graft occlusion or stenosis.</p></div><div><h3>Methods</h3><p>This study includes DUS examinations of 663 patients who had bypass graft operations done between January 2009 and June 2022. Only examinations without missing values were included. We developed two RNNs (a bidirectional long short-term memory unit and a bidirectional gated recurrent unit) to predict bypass graft occlusion and stenosis based on peak systolic velocities collected in the 2 to 5 previous DUS examinations. We excluded the examinations with missing values and split our data into training and test sets. Then, we applied 10-fold cross-validation on training to optimize the hyperparameters and compared models using the test data.</p></div><div><h3>Results</h3><p>The bidirectional long short-term memory unit model can gain an overall sensitivity of 0.939, specificity of 0.963, and area under the curve of 0.950 on the prediction of bypass graft occlusion, and an overall sensitivity of 0.915, specificity of 0.909, and area under the curve of 0.912 predicting the development of a future critical stenosis. The results on different bypass types show that the system performs differently on different types. The results on subcohorts based on gender, smoking status, and comorbidities show that the performance on current smokers is lower than the never smoker.</p></div><div><h3>Conclusions</h3><p>We found that RNNs can gain good sensitivity, specificity, and accuracy for the detection of impending bypass graft occlusion or the future development of a critical bypass graft stenosis using all the available peak systolic velocity data in the present and previous bypass graft DUS examinations. Integrating clinical data, including demographics, social determinants, medication, and other risk factors, together with the DUS examination may result in further improvements.</p></div><div><h3>Clinical Relevance</h3><p>Detecting bypass graft failure before it occurs is important clinically to prevent amputations, salvage limbs, and save lives. Current methods evaluating screening duplex ultrasound examinations have a significant failure rate for detecting a bypass graft at risk for failure. Artificial intelligence using recurrent neural networks has the potential to improve the detection of at-risk bypass graft before they fail. Additionally, artificial intelligence is in the news and is being applied to many fields. Vascular surgeons need to know its potential to improve vascular outcomes.</p","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"5 ","pages":"Article 100192"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350324000038/pdfft?md5=e64b464b16fd4434244d34e5952f1fb4&pid=1-s2.0-S2666350324000038-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139814472","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}
Pub Date : 2024-01-01DOI: 10.1016/j.jvssci.2024.100194
Ali Navi PhD, FRCS , Hemanshu Patel MRCS , Xu Shiwen PhD , Daryll Baker PhD, FRCS , David Abraham PhD , Janice Tsui MD, FRCS
Objective
Toll-like receptors (TLRs) are key pattern recognition receptors in the innate immune system. In particular, the TLR4-mediated immune response has been implicated in ischemia-induced tissue injury. Mounting evidence supports a detrimental role of the innate immune system in the pathophysiology of skeletal muscle damage in patients with chronic limb-threatening ischemia (CLTI), in whom patient-oriented functional outcomes are poor. The overall aim of this study was to investigate the potential role of TLR4 in skeletal muscle dysfunction and damage in CLTI.
Methods
The role of TLR4 in ischemic muscle was investigated by (1) studying TLR4 expression and distribution in human gastrocnemius muscle biopsies, (2) evaluating the functional consequences of TLR4 inhibition in myotubes derived from human muscle biopsies, and (3) assessing the therapeutic potential of modulating TLR4 signaling in ischemic muscle in a mouse hindlimb ischemia model.
Results
TLR4 was found to be expressed in human muscle biopsies, with significant upregulation in samples from patients with CLTI. In vitro studies using cultured human myotubes demonstrated upregulation of TLR4 in ischemia, with activation of the downstream signaling pathway. Inhibition of TLR4 before ischemia was associated with reduced ischemia-induced apoptosis. Upregulation of TLR4 also occurred in ischemia in vivo and TLR4 inhibition was associated with decreased inflammatory cell infiltration and diminished apoptosis in the ischemic limb.
Conclusions
TLR4 is upregulated and activated in ischemic skeletal muscle in patients with CLTI. Modulating TLR4 signaling in vitro and in vivo was associated with attenuation of ischemia-induced skeletal muscle damage. This strategy could be explored further for potential clinical application.
{"title":"Role of toll-like receptor 4 in skeletal muscle damage in chronic limb-threatening ischemia","authors":"Ali Navi PhD, FRCS , Hemanshu Patel MRCS , Xu Shiwen PhD , Daryll Baker PhD, FRCS , David Abraham PhD , Janice Tsui MD, FRCS","doi":"10.1016/j.jvssci.2024.100194","DOIUrl":"10.1016/j.jvssci.2024.100194","url":null,"abstract":"<div><h3>Objective</h3><p>Toll-like receptors (TLRs) are key pattern recognition receptors in the innate immune system. In particular, the TLR4-mediated immune response has been implicated in ischemia-induced tissue injury. Mounting evidence supports a detrimental role of the innate immune system in the pathophysiology of skeletal muscle damage in patients with chronic limb-threatening ischemia (CLTI), in whom patient-oriented functional outcomes are poor. The overall aim of this study was to investigate the potential role of TLR4 in skeletal muscle dysfunction and damage in CLTI.</p></div><div><h3>Methods</h3><p>The role of TLR4 in ischemic muscle was investigated by (1) studying TLR4 expression and distribution in human gastrocnemius muscle biopsies, (2) evaluating the functional consequences of TLR4 inhibition in myotubes derived from human muscle biopsies, and (3) assessing the therapeutic potential of modulating TLR4 signaling in ischemic muscle in a mouse hindlimb ischemia model.</p></div><div><h3>Results</h3><p>TLR4 was found to be expressed in human muscle biopsies, with significant upregulation in samples from patients with CLTI. In vitro studies using cultured human myotubes demonstrated upregulation of TLR4 in ischemia, with activation of the downstream signaling pathway. Inhibition of TLR4 before ischemia was associated with reduced ischemia-induced apoptosis. Upregulation of TLR4 also occurred in ischemia in vivo and TLR4 inhibition was associated with decreased inflammatory cell infiltration and diminished apoptosis in the ischemic limb.</p></div><div><h3>Conclusions</h3><p>TLR4 is upregulated and activated in ischemic skeletal muscle in patients with CLTI. Modulating TLR4 signaling in vitro and in vivo was associated with attenuation of ischemia-induced skeletal muscle damage. This strategy could be explored further for potential clinical application.</p></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"5 ","pages":"Article 100194"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350324000051/pdfft?md5=d603bb34696f721ac8ea04bebe8fb57c&pid=1-s2.0-S2666350324000051-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139888888","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}
Pub Date : 2023-01-01DOI: 10.1016/j.jvssci.2023.100100
Dahlia M. Kenawy MD , Moataz Elsisy PhD , Mahmoud Abdel-Rasoul MS, MPH , Tanner L. Koppert MS , Marlene I. Garcia-Neuer MD, MSc , Youngjae Chun PhD , Bryan W. Tillman MD, PhD
Objective
Noncompressible torso hemorrhage is a high-mortality injury. We previously reported improved outcomes with a retrievable rescue stent graft to temporize aortic hemorrhage in a porcine model while maintaining distal perfusion. A limitation was that the original cylindrical stent graft design prohibited simultaneous vascular repair, given the concern for suture ensnarement of the temporary stent. We hypothesized that a modified, dumbbell-shaped design would preserve distal perfusion and also offer a bloodless plane in the midsection, facilitating repair with the stent graft in place and improve the postrepair hemodynamics.
Methods
In an Institutional Animal Care and Use Committee-approved terminal porcine model, a custom retrievable dumbbell-shaped rescue stent graft (dRS) was fashioned from laser-cut nitinol and polytetrafluoroethylene covering and compared with aortic cross-clamping. Under anesthesia, the descending thoracic aorta was injured and then repaired with cross-clamping (n = 6) or dRS (n = 6). Angiography was performed in both groups. Operations were divided into phases: (1) baseline, (2) thoracic injury with either cross-clamp or dRS deployed, and (3) recovery, after which the clamp or dRS were removed. Target blood loss was 22% to simulate class II or III hemorrhagic shock. Shed blood was recovered with a Cell Saver and reinfused for resuscitation. Renal artery flow rates were recorded at baseline and during the repair phase and reported as a percentage of cardiac output. Phenylephrine pressor requirements were recorded.
Results
In contrast with cross-clamped animals, dRS animals demonstrated both operative hemostasis and preserved flow beyond the dRS angiographically. Recovery phase mean arterial pressure, cardiac output, and right ventricular end-diastolic volume were significantly higher in dRS animals (P = .033, P = .015, and P = .012, respectively). Whereas distal femoral blood pressures were absent during cross-clamping, among the dRS animals, the carotid and femoral MAPs were not significantly different during the injury phase (P = .504). Cross-clamped animals demonstrated nearly absent renal artery flow, in contrast with dRS animals, which exhibited preserved perfusion (P<.0001). Femoral oxygen levels (partial pressure of oxygen) among a subset of animals further confirmed greater distal oxygenation during dRS deployment compared with cross-clamping (P = .006). After aortic repair and clamp or stent removal, cross-clamped animals demonstrated more significant hypotension, as demonstrated by increased pressor requirements over stented animals (P = .035).
Conclusions
Compared with aortic cross-clamping, the dRS model demonstrated superior distal perfusion, while also facilitating simultaneous hemorrhage control and aortic repair. This study demonstrates a promising
{"title":"A dumbbell rescue stent graft facilitates clamp-free repair of aortic injury in a porcine model","authors":"Dahlia M. Kenawy MD , Moataz Elsisy PhD , Mahmoud Abdel-Rasoul MS, MPH , Tanner L. Koppert MS , Marlene I. Garcia-Neuer MD, MSc , Youngjae Chun PhD , Bryan W. Tillman MD, PhD","doi":"10.1016/j.jvssci.2023.100100","DOIUrl":"10.1016/j.jvssci.2023.100100","url":null,"abstract":"<div><h3>Objective</h3><p>Noncompressible torso hemorrhage is a high-mortality injury. We previously reported improved outcomes with a retrievable rescue stent graft to temporize aortic hemorrhage in a porcine model while maintaining distal perfusion. A limitation was that the original cylindrical stent graft design prohibited simultaneous vascular repair, given the concern for suture ensnarement of the temporary stent. We hypothesized that a modified, dumbbell-shaped design would preserve distal perfusion and also offer a bloodless plane in the midsection, facilitating repair with the stent graft in place and improve the postrepair hemodynamics.</p></div><div><h3>Methods</h3><p>In an Institutional Animal Care and Use Committee-approved terminal porcine model, a custom retrievable dumbbell-shaped rescue stent graft (dRS) was fashioned from laser-cut nitinol and polytetrafluoroethylene covering and compared with aortic cross-clamping. Under anesthesia, the descending thoracic aorta was injured and then repaired with cross-clamping (n = 6) or dRS (n = 6). Angiography was performed in both groups. Operations were divided into phases: (1) baseline, (2) thoracic injury with either cross-clamp or dRS deployed, and (3) recovery, after which the clamp or dRS were removed. Target blood loss was 22% to simulate class II or III hemorrhagic shock. Shed blood was recovered with a Cell Saver and reinfused for resuscitation. Renal artery flow rates were recorded at baseline and during the repair phase and reported as a percentage of cardiac output. Phenylephrine pressor requirements were recorded.</p></div><div><h3>Results</h3><p>In contrast with cross-clamped animals, dRS animals demonstrated both operative hemostasis and preserved flow beyond the dRS angiographically. Recovery phase mean arterial pressure, cardiac output, and right ventricular end-diastolic volume were significantly higher in dRS animals (<em>P</em> = .033, <em>P</em> = .015, and <em>P</em> = .012, respectively). Whereas distal femoral blood pressures were absent during cross-clamping, among the dRS animals, the carotid and femoral MAPs were not significantly different during the injury phase (<em>P</em> = .504). Cross-clamped animals demonstrated nearly absent renal artery flow, in contrast with dRS animals, which exhibited preserved perfusion (<em>P</em><.0001). Femoral oxygen levels (partial pressure of oxygen) among a subset of animals further confirmed greater distal oxygenation during dRS deployment compared with cross-clamping (<em>P</em> = .006). After aortic repair and clamp or stent removal, cross-clamped animals demonstrated more significant hypotension, as demonstrated by increased pressor requirements over stented animals (<em>P</em> = .035).</p></div><div><h3>Conclusions</h3><p>Compared with aortic cross-clamping, the dRS model demonstrated superior distal perfusion, while also facilitating simultaneous hemorrhage control and aortic repair. This study demonstrates a promising","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"4 ","pages":"Article 100100"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10068254/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9612628","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}
This study was conducted to investigate in vitro proangiogenic and anti-inflammatory phenotypes and functions and the in vivo efficacy and safety of quality and quantity (QQ) media-cultured mononuclear cells (MNCs) compared with standard cultured MNCs from the peripheral blood of patients with chronic limb-threatening ischemia (CLTI) with atherosclerotic risk factors.
Methods
Peripheral blood MNCs (PBMNCs) from patients with CLTI were cultured in QQ culture media or standard culture media. Phenotypic analysis of progenitor cells (CD34+CD133+), M2 macrophages (CD206+), and inactivated T regulatory cells (CD4+CD25+CD127+), colony-forming assay, and tube formation assay of QQ media-cultured MNCs (QQMNCs) and PBMNCs, were conducted. Intramuscular transplantation of QQMNCs or PBMNCs was performed in the ischemic hindlimb model. The clinical appearance of ischemic limbs was observed, and blood flow in ischemic limbs was measured using a laser Doppler perfusion imager. Outcomes were compared between the QQMNC and PBMNC groups.
Results
Twenty patients with CLTI were included. The mean percentages of CD34+ cells, CD133+ cells, CD34+CD133+ progenitor cells, CD206+ cells, colony-forming cells, and tube formation were significantly higher in the QQMNCs. The mean percentage of CD4+CD25+CD127+ cells was significantly lower in QQMNC. The colony-forming unit count and Dil-acetylated low-density lipoprotein uptake were significantly greater in QQMNCs. The clinical appearance of post-QQMNC-injected limbs was less severe than the appearance of post-PBMNC-injected limbs. Limb perfusion was significantly better in the QQMNCs.
Conclusions
Proangiogenic and anti-inflammatory phenotypes of MNCs cultured in QQ culture media were reproducible. Intramuscular QQMNC transplantation was safe and resulted in better reperfusion of ischemic hindlimbs compared with PBMNCs.
{"title":"The quality and quantity media-cultured mononuclear cell transplantation is safe and effective in ischemic hindlimb mouse model","authors":"Wanchai Chinchalongporn MD , Nuttapol Chruewkamlow PhD , Nuttawut Sermsathanasawadi MD, PhD , Kosit Vorateera MD , Suthatip Jintaworn MSc , Chumpol Wongwanit MD , Chanean Ruangsetakit MSc, MD","doi":"10.1016/j.jvssci.2023.100129","DOIUrl":"https://doi.org/10.1016/j.jvssci.2023.100129","url":null,"abstract":"<div><h3>Objective</h3><p>This study was conducted to investigate in vitro proangiogenic and anti-inflammatory phenotypes and functions and the in vivo efficacy and safety of quality and quantity (QQ) media-cultured mononuclear cells (MNCs) compared with standard cultured MNCs from the peripheral blood of patients with chronic limb-threatening ischemia (CLTI) with atherosclerotic risk factors.</p></div><div><h3>Methods</h3><p>Peripheral blood MNCs (PBMNCs) from patients with CLTI were cultured in QQ culture media or standard culture media. Phenotypic analysis of progenitor cells (CD34<sup>+</sup>CD133<sup>+</sup>), M2 macrophages (CD206<sup>+</sup>), and inactivated T regulatory cells (CD4<sup>+</sup>CD25<sup>+</sup>CD127<sup>+</sup>), colony-forming assay, and tube formation assay of QQ media-cultured MNCs (QQMNCs) and PBMNCs, were conducted. Intramuscular transplantation of QQMNCs or PBMNCs was performed in the ischemic hindlimb model. The clinical appearance of ischemic limbs was observed, and blood flow in ischemic limbs was measured using a laser Doppler perfusion imager. Outcomes were compared between the QQMNC and PBMNC groups.</p></div><div><h3>Results</h3><p>Twenty patients with CLTI were included. The mean percentages of CD34<sup>+</sup> cells, CD133<sup>+</sup> cells, CD34<sup>+</sup>CD133<sup>+</sup> progenitor cells, CD206<sup>+</sup> cells, colony-forming cells, and tube formation were significantly higher in the QQMNCs. The mean percentage of CD4<sup>+</sup>CD25<sup>+</sup>CD127<sup>+</sup> cells was significantly lower in QQMNC. The colony-forming unit count and Dil-acetylated low-density lipoprotein uptake were significantly greater in QQMNCs. The clinical appearance of post-QQMNC-injected limbs was less severe than the appearance of post-PBMNC-injected limbs. Limb perfusion was significantly better in the QQMNCs.</p></div><div><h3>Conclusions</h3><p>Proangiogenic and anti-inflammatory phenotypes of MNCs cultured in QQ culture media were reproducible. Intramuscular QQMNC transplantation was safe and resulted in better reperfusion of ischemic hindlimbs compared with PBMNCs.</p></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"4 ","pages":"Article 100129"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350323000330/pdfft?md5=8aa8028b9e963dd22b3212eaad87425f&pid=1-s2.0-S2666350323000330-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91591125","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}
Pub Date : 2023-01-01DOI: 10.1016/j.jvssci.2023.100132
Alan Dardik , John A. Curci , Gale L. Tang , Ulf Hedin , Nirvana Sadaghianloo , Trisha L. Roy , Ronald L. Dalman
{"title":"We need more vascular research","authors":"Alan Dardik , John A. Curci , Gale L. Tang , Ulf Hedin , Nirvana Sadaghianloo , Trisha L. Roy , Ronald L. Dalman","doi":"10.1016/j.jvssci.2023.100132","DOIUrl":"https://doi.org/10.1016/j.jvssci.2023.100132","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"4 ","pages":"Article 100132"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350323000366/pdfft?md5=4aca1207ba59639cf84850819f0e2c1f&pid=1-s2.0-S2666350323000366-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91957444","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}
Pub Date : 2023-01-01DOI: 10.1016/j.jvssci.2023.100169
Isra Marei , Binitha Thomas , Blerina Ahmetaj-Shala , Omar Chidiac , Tanwir Habib , El-Naas Ahmed , Anam Ehtesham , Azwa Dilawar , Leena Elsheikh Aboidris , Muhammed Jameesh Moidy , Amin Jayyousi , Jassim M. Al Suwaidi , Charbel A. Abi Khalil , Jane A. Mitchell , Chris R. Triggle
{"title":"Altered Gene Expression and Impaired Repair Functions of Circulating Endothelial Colony-Forming Cells From Diabetic Patients","authors":"Isra Marei , Binitha Thomas , Blerina Ahmetaj-Shala , Omar Chidiac , Tanwir Habib , El-Naas Ahmed , Anam Ehtesham , Azwa Dilawar , Leena Elsheikh Aboidris , Muhammed Jameesh Moidy , Amin Jayyousi , Jassim M. Al Suwaidi , Charbel A. Abi Khalil , Jane A. Mitchell , Chris R. Triggle","doi":"10.1016/j.jvssci.2023.100169","DOIUrl":"https://doi.org/10.1016/j.jvssci.2023.100169","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"4 ","pages":"Article 100169"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350323000731/pdfft?md5=18cbde0917cc4fa3087223f665524c1b&pid=1-s2.0-S2666350323000731-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139107089","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}
Pub Date : 2023-01-01DOI: 10.1016/j.jvssci.2023.100168
Michelle L. Roberts, Justin Westhoff, Jingli Wang, Rong Ying, Susanne M. Cabrera, Michael E. Widlansky
{"title":"Phenotypic and Molecular Effects of Testosterone Gender-affirming Hormone Therapy on the Vascular Endothelium of Transgender Men","authors":"Michelle L. Roberts, Justin Westhoff, Jingli Wang, Rong Ying, Susanne M. Cabrera, Michael E. Widlansky","doi":"10.1016/j.jvssci.2023.100168","DOIUrl":"https://doi.org/10.1016/j.jvssci.2023.100168","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"4 ","pages":"Article 100168"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266635032300072X/pdfft?md5=eca6ab7c74b02b56840ebc09e05ef2e9&pid=1-s2.0-S266635032300072X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139108510","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}
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