JVS-vascular science最新文献

{"title":"Sox17 mediates venous adaptive remodeling after arteriovenous fistula creation","authors":"Yukihiko Aoyagi MD , Andrew W. Schwartz BS , Zhuo Li MD, PhD , Hualong Bai MD, PhD , Bryan Ho MD , Cayetana Lazcano-Etchebarne BS , Luis Gonzalez PhD , Yuichi Ohashi MD , Masaki Kano MD , Bogdan Yatsula PhD , Cassius Iyad Ochoa Chaar MD, MPH, MS , Kathleen Martin PhD , Roberto Vazquez-Padron PhD , Guohao Dai PhD , Alan Dardik MD, PhD","doi":"10.1016/j.jvssci.2025.100392","DOIUrl":"10.1016/j.jvssci.2025.100392","url":null,"abstract":"<div><h3>Objective</h3><div>Mature arteriovenous fistulae (AVF) are the gold standard vascular access allowing hemodialysis for patients with end-stage kidney disease. The rate of AVF failure remains high, reflecting an incomplete understanding of the biology of AVF maturation and failure. Sox17 is a transcription factor indispensable for the acquisition and maintenance of endothelial arterial identity. Because endothelial cells (EC) acquire dual arteriovenous identity after AVF creation, we determined whether Sox17 mediates venous remodeling in AVF.</div></div><div><h3>Methods</h3><div>Human preaccess vein, failed AVF, and mature AVF from second stage basilic vein transpositions were analyzed using immunofluorescence and single cell sequencing to determine Sox17 expression. Aortocaval AVF created in 9- to 11-week-old C57BL/6J mice were harvested on day 7 or 21 for analysis with Western blot, quantitative polymerase chain reaction, histology, or immunofluorescence to assess Sox17 immunoreactivity in EC. Doppler ultrasound examination confirmed AVF patency and measured inferior vena cava and aortic flow velocity and diameter. Sox17 knockdown was performed using short hairpin RNA lentivirus delivered perivascularly immediately after AVF creation. Analysis of variance and <em>t</em> tests were used for statistical analyses.</div></div><div><h3>Results</h3><div>Sox17 was significantly elevated in mature human AVF compared with control veins (<em>P</em> = .02) and in mature human AVF compared with failed human AVF (<em>P</em> = .04). In the mouse AVF, Sox17 expression was also significantly upregulated compared with sham-operated mice (<em>P</em> = .0012 in male mice; <em>P</em> = .0062 in female mice). Sox17 immunoreactivity was highest on days 7 and 21 and returned to near sham levels at day 42. In both human and mouse AVF, Sox17 expression was localized to the nucleus of EC. Sox17 knockdown mice had impaired venous remodeling, characterized by a smaller inferior vena cava diameter (<em>P</em> = .001) and thinner intima-media layers relative to control AVF (<em>P</em> = .015). Sox17 knockdown mice had decreased JAG1 expression (<em>P</em> = .008) and decreased smooth muscle cell proliferation (<em>P</em> = .03) on day 7.</div></div><div><h3>Conclusions</h3><div>Sox17 is a novel mediator of venous remodeling during AVF maturation. Sox17 is upregulated in the venous outflow of AVF, and Sox17 knockdown causes impaired outward remodeling and wall thickening. Manipulation of endothelial vascular identity may be a translational approach to regulate venous remodeling and improve AVF patency.</div></div><div><h3>Clinical Relevance</h3><div>Arteriovenous fistula (AVF) failure remains a major barrier to long-term hemodialysis access in patients with end-stage kidney disease. This study identifies Sox17 as a key transcription factor mediating venous remodeling after AVF creation. Sox17 expression is elevated in mature human AVF and affects outward remodeling, ","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100392"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145264952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contrast-enhanced ultrasound microbubble uptake and abnormal plasma biomarkers are seen in patients with abdominal aortic aneurysms","authors":"Adham N. Abou Ali MD ,&nbsp;Patrick Cherfan MD ,&nbsp;Ashraf G. Taha MD ,&nbsp;Michel S. Makaroun MD ,&nbsp;Yingze Zhang PhD ,&nbsp;Xucai X. Chen PhD ,&nbsp;Flordeliza S. Villanueva MD ,&nbsp;Rabih A. Chaer MD","doi":"10.1016/j.jvssci.2025.100284","DOIUrl":"10.1016/j.jvssci.2025.100284","url":null,"abstract":"<div><h3>Objective</h3><div>Abdominal aortic aneurysm (AAA) growth is unpredictable. We hypothesize that contrast-enhanced ultrasound (CEUS) imaging and plasma inflammatory biomarkers (PIBs) may detect AAA wall inflammation.</div></div><div><h3>Methods</h3><div>Patients with an AAA diameter ≥4 cm had CEUS and PIB testing at enrollment and every 6 months. Microbubble replenishment was analyzed via manually drawn regions of the aortic wall. Aneurysm growth, rupture, and repair were recorded. PIB testing was analyzed using biomarker panels. Independent and paired <em>t</em>-tests were used to detect differences in PIB levels. Logistic regression was used to study the association between PIBs, microbubble uptake, and AAA growth.</div></div><div><h3>Results</h3><div>A total of 59 patients were enrolled (mean age, 68.8 ± 8.6 years; 13.6% female; 93.2% White). Mean AAA size on presentation was 41.6 ± 6.7 mm. Microbubble uptake was seen in 36 patients (61%). Patients with AAA had high baseline levels of Cystatin C and interferon-γ and low levels of macrophage migration inhibitory factor. Microbubble uptake was seen in 59% of patients with ≥5 mm AAA growth but was not predictive of growth on logistic regression.</div></div><div><h3>Conclusions</h3><div>We have demonstrated that microbubble uptake with CEUS is seen in the aortic wall/intraluminal thrombus of patients with AAA. CEUS and PIBs could provide insight into aneurysm behavior in newly diagnosed AAA.</div></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100284"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantifying the effect of IMPEDE-FX packing rate and volume on pressure-normalized principal wall strain in an idealized 3D-printed aneurysm model","authors":"Baqir Kedwai BHSc ,&nbsp;Joshua Geiger MD ,&nbsp;Sam Najjar BS ,&nbsp;Joel Kruger MD ,&nbsp;Michael Richards PhD ,&nbsp;Chung Yeh BS ,&nbsp;Mary Dennehy BS ,&nbsp;Michael Stoner MD ,&nbsp;Doran Mix MD","doi":"10.1016/j.jvssci.2025.100287","DOIUrl":"10.1016/j.jvssci.2025.100287","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;This study aimed to quantify the nonbiologic effects of Shape Memory IMPEDE-FX embolization plug deployment rate and packing volume on pressure-normalized wall strain (&lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mover&gt;&lt;msub&gt;&lt;mi&gt;ε&lt;/mi&gt;&lt;mrow&gt;&lt;mi&gt;ρ&lt;/mi&gt;&lt;mo&gt;+&lt;/mo&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;mo&gt;¯&lt;/mo&gt;&lt;/mover&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;/PP) of an idealized 3D-printed abdominal aortic aneurysm model.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;An endograft was deployed into an abdominal aortic aneurysm model and connected to an industry-validated hemodynamic simulator. Plugs were deployed into the excluded sac to packing volumes of 100%, 200%, 300%, and 400% under two conditions: (1) sequential and (2) immediate deployment. Axial ultrasound images were taken for each packing volume. Frame-to-frame displacements of the aneurysm wall were measured with ultrasound elastography over one cardiac cycle and normalized to the circuit's pulse pressure to calculate the mean principal strain (&lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mover&gt;&lt;msub&gt;&lt;mi&gt;ε&lt;/mi&gt;&lt;mrow&gt;&lt;mi&gt;ρ&lt;/mi&gt;&lt;mo&gt;+&lt;/mo&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;mo&gt;¯&lt;/mo&gt;&lt;/mover&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;/PP).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;In the 100% packing condition, &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mover&gt;&lt;msub&gt;&lt;mi&gt;ε&lt;/mi&gt;&lt;mrow&gt;&lt;mi&gt;ρ&lt;/mi&gt;&lt;mo&gt;+&lt;/mo&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;mo&gt;¯&lt;/mo&gt;&lt;/mover&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;/PP was +113% above baseline at 15 minutes. After sequential deployment to 400%, the &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mover&gt;&lt;msub&gt;&lt;mi&gt;ε&lt;/mi&gt;&lt;mrow&gt;&lt;mi&gt;ρ&lt;/mi&gt;&lt;mo&gt;+&lt;/mo&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;mo&gt;¯&lt;/mo&gt;&lt;/mover&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;/PP trended down to +43% above baseline. Immediate packing was associated with a greater &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mover&gt;&lt;msub&gt;&lt;mi&gt;ε&lt;/mi&gt;&lt;mrow&gt;&lt;mi&gt;ρ&lt;/mi&gt;&lt;mo&gt;+&lt;/mo&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;mo&gt;¯&lt;/mo&gt;&lt;/mover&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;/PP reduction than sequential packing. When packed immediately to 400%, the &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mover&gt;&lt;msub&gt;&lt;mi&gt;ε&lt;/mi&gt;&lt;mrow&gt;&lt;mi&gt;ρ&lt;/mi&gt;&lt;mo&gt;+&lt;/mo&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;mo&gt;¯&lt;/mo&gt;&lt;/mover&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;/PP was −6.7% below baseline.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;These modeling data suggest that an immediate deployment strategy and higher plug packing volumes are associated with lower &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mover&gt;&lt;msub&gt;&lt;mi&gt;ε&lt;/mi&gt;&lt;mrow&gt;&lt;mi&gt;ρ&lt;/mi&gt;&lt;mo&gt;+&lt;/mo&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;mo&gt;¯&lt;/mo&gt;&lt;/mover&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;/PP, which has been associated with decreased sac growth rates.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Clinical Relevance&lt;/h3&gt;&lt;div&gt;The present findings suggest that rapid, high-volume filling of IMPEDE-FX embolization plugs results in a reduction in wall &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mover&gt;&lt;msub&gt;&lt;mi&gt;ε&lt;/mi&gt;&lt;mrow&gt;&lt;mi&gt;ρ&lt;/mi&gt;&lt;mo&gt;+&lt;/mo&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;mo&gt;¯&lt;/mo&gt;&lt;/mover&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;/PP, independent of thrombus formation. Fully expanded embolization plugs in aggregate limit pulsatile aortic sac displacement likely contribute to a greater reduction in overall wall strain compared with low packing volumes. These findings may inform clinical application for this device, supporting a rapid and high-volume deployment strategy for greater reduction in &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mover&gt;&lt;msub&gt;&lt;mi&gt;ε&lt;/mi&gt;&lt;mrow&gt;&lt;mi&gt;ρ&lt;/mi&gt;&lt;mo&gt;+&lt;/mo&gt;","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100287"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Narrative review of endothelial cell metabolism and aberrations in atherosclerosis and peripheral artery disease","authors":"Sean M. Carr PhD,&nbsp;Ottis Scrivner PhD,&nbsp;Katherine Elizabeth Hekman MD, PhD","doi":"10.1016/j.jvssci.2025.100285","DOIUrl":"10.1016/j.jvssci.2025.100285","url":null,"abstract":"<div><h3>Objective</h3><div>Several decades of medical research have shown an intricate and definitive connection between dysfunctional endothelium and cardiovascular disorders, including atherosclerosis and peripheral artery disease (PAD). Initial investigations into endothelial cell (EC) physiology highlighted excretion of protein-based growth factors and their signaling pathways with highly specific targets. However, more recent research has focused on nonprotein metabolic signaling.</div></div><div><h3>Methods</h3><div>A narrative review methodology was used. The review involved keyword searches of electronic databases, including Medline and ScienceDirect, conducted in March through October 2022. Review search terms included “endothelial cell metabolism,” “peripheral artery disease metabolism,” “angiogenesis metabolism,” and “endothelial cell metabolic regulation.” The search included primary research articles and subject matter narrative reviews. Abstracts were reviewed for English-language articles published between 2003 and 2022 and supplemented with targeted reference tracing.</div></div><div><h3>Results</h3><div>Small-molecular-weight metabolites have been found to regulate key EC functions such as angiogenesis directly. More specifically, they impact EC behavior through control of energy production, de novo biomass synthesis, redox homeostasis, and production of gases like nitric oxide and hydrogen sulfide. Recent investigations targeting these metabolic pathways have yielded preliminary success in correcting undesirable endothelial dysfunction in atherosclerosis and PAD.</div></div><div><h3>Conclusions</h3><div>Further investigations into therapeutic targeting of EC metabolism may yield novel approaches for treating PAD.</div></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100285"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143927449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Micro- and nanoplastics are elevated in femoral atherosclerotic plaques compared with undiseased arteries","authors":"Pierce L. Massie MD ,&nbsp;Marcus A. Garcia PharmD ,&nbsp;Daniel Gallego MD ,&nbsp;Christopher Schlosser PA ,&nbsp;Aerlin Decker BSPS ,&nbsp;Rui Liu PhD ,&nbsp;Milad MazloumiBakhshayesh MPharm ,&nbsp;Deepali Kulkarni MD ,&nbsp;Matthew P. Justus MS ,&nbsp;Carolyn Pace BS ,&nbsp;Rowza T. Rumma MD ,&nbsp;Matthew J. Campen PhD ,&nbsp;Ross M. Clark MD, MBA, FSVS","doi":"10.1016/j.jvssci.2025.100393","DOIUrl":"10.1016/j.jvssci.2025.100393","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;As plastic production continues to accelerate, the byproducts increasingly fill the environment. Once degraded into micronanoplastics (MNPs), particles may circulate into food, drinking water, or air. Nascent literature has demonstrated MNP bioaccumulation within human tissues, such as the blood, brain, and solid organs. Only recently have MNPs been identified within thrombi and atherosclerotic plaques of diseased blood vessels, and these findings have been associated with adverse clinical outcomes. Data on MNP content in infrainguinal arterial occlusive disease is currently lacking, however. We investigated MNP presence within femoral artery plaques and examined patient clinical variables to characterize their associations in a territory commonly affected by peripheral arterial disease.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Common femoral artery plaques were collected from patients undergoing common femoral endarterectomy for medically refractory lower extremity peripheral arterial disease. These samples were then sectioned, frozen, and analyzed using pyrolysis gas chromatography/mass spectrometry for MNP content by polymer. A total of 12 polymers were investigated in triplicate. A group of decedent patients without clinical atherosclerosis served as control with whole carotid artery tissue used for a similar analysis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 10 plaques from 8 patients were collected for the plaque group, and 30 whole carotids were gathered from decedents and age matched to the plaque group. The total MNP concentration was 80-fold higher in femoral plaque compared with the control group 3234 μg/g tissue vs 40.68 μg/g tissue for control arteries (&lt;em&gt;P&lt;/em&gt; = .0001). By polymer, polyethylene, polystyrene, acrylonitrile butadiene styrene, styrene-butadiene, polyvinylchloride, polyethylene terephthalate, poly(methyl methacrylate), polycarbonate, nylon 66, and nylon 6 were all significantly elevated compared with control tissue. No differences in sex were detected in either group. Polypropylene content was positively correlated with age (&lt;em&gt;P&lt;/em&gt; = .011). Within the plaque group, patients undergoing revascularization for chronic limb-threatening ischemia had a greater than three-fold concentration of PP (247 ± 113.6 μg/g vs 71.9 ± 73.5 μg/g) and 10-fold concentration of polyurethane (17.4 ± 12.1 μg/g vs 1.69 ± 2.9 μg/g) compared with those with claudication (&lt;em&gt;P&lt;/em&gt; = .0381 and &lt;em&gt;P&lt;/em&gt; = .0238, respectively).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;This study demonstrates a greater accumulation of MNPs in common femoral artery plaques compared with nonatherosclerotic artery tissue. This finding further supports the premise that, despite similarities in age between groups, MNPs tend to be represented heavily in atherosclerotic tissues. Patients with chronic limb-threatening ischemia showed a greater concentration of some polymers compared with those with claudication, raising the question of","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100393"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis between abdominal aortic aneurysm and popliteal artery aneurysm","authors":"Marcos Vinícius Melo de Oliveira MD, PhD ,&nbsp;Alexandre Malta Brandão MD, PhD ,&nbsp;Gina Camillo Rocha Silvestre BS ,&nbsp;Alexandre Queiroz Silva BS ,&nbsp;Michele Alberto Marques BS ,&nbsp;Marcia Martins Reis PhD ,&nbsp;Maria de Lourdes Higuchi MD, PhD ,&nbsp;Erasmo Simão da Silva MD, PhD","doi":"10.1016/j.jvssci.2024.100279","DOIUrl":"10.1016/j.jvssci.2024.100279","url":null,"abstract":"<div><h3>Objective</h3><div>Infrarenal abdominal aortic aneurysm (AAA) and popliteal artery aneurysm (PAA) are localized arterial dilatations with distinct clinical outcomes. This study aimed to comprehensively compare these two types of aneurysms' biomechanical, histological, and immunohistochemical characteristics.</div></div><div><h3>Methods</h3><div>This study included 180 patients with AAA and 18 with PAA. Medical history and imaging data were collected. Biomechanical testing assessed arterial wall mechanical strength and elasticity, and histological and immunohistochemical analyses examined tissue composition and inflammatory markers.</div></div><div><h3>Results</h3><div>PAA wall fragments demonstrate higher failure strain energy (13.36 N/m² vs 9.95 N/m²; <em>P</em> = .023), a measure of mechanical strength. Regarding immunohistochemical markers, AAA exhibited more B lymphocyte cells in the adventitia (CD20 1475.50 vs 320; <em>P</em> = .003) compared with PAA. Additionally, AAA demonstrated more adipogenic differentiation in the adventitia (PPARgamma 4854.50 vs 778; <em>P</em> = .009), whereas PAA showed more adipogenic differentiation in the intima (KLF5 283.50 vs 77.50; <em>P</em> = .039).</div></div><div><h3>Conclusions</h3><div>PAA wall fragments demonstrate greater mechanical strength compared with AAA wall fragments. In contrast, AAA walls contain a greater number of B lymphocytes within the adventitia compared with PAA walls. Adipogenic differentiation is more pronounced in the adventitia of AAA than in PAA, whereas in PAA, it is more prominent in the intima compared with AAA.</div></div><div><h3>Clinical Relevance</h3><div>The clinical significance of this study lies in its potential to enhance our understanding of the distinct pathophysiological mechanisms underlying abdominal aortic aneurysms, which is often associated with rupture, and popliteal artery aneurysms, which are more prone to thrombosis and distal embolization. By comprehensively comparing the biomechanical, histological, and immunohistochemical aspects of these two aneurysm types, the study aims to illuminate the factors contributing to their differing clinical presentations and outcomes.</div></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100279"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143139172","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}

{"title":"Information for Readers","authors":"","doi":"10.1016/j.jvssci.2025.100402","DOIUrl":"10.1016/j.jvssci.2025.100402","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100402"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma proteome-wide Mendelian randomization reveals the association of extracellular matrix proteins with abdominal aortic aneurysm","authors":"Samuel Khodursky PhD ,&nbsp;Shuai Yuan PhD ,&nbsp;Joshua M. Spin MD, PhD ,&nbsp;Philip S. Tsao PhD ,&nbsp;Michael G. Levin MD ,&nbsp;Scott M. Damrauer MD","doi":"10.1016/j.jvssci.2025.100290","DOIUrl":"10.1016/j.jvssci.2025.100290","url":null,"abstract":"<div><h3>Objective</h3><div>Abdominal aortic aneurysm (AAA) is a common and life-threatening vascular disease. Genetic studies have identified numerous risk loci, many potentially encoding plasma proteins. However, the causal effects of plasma proteins on AAAs have not been thoroughly studied. We used genetic causal inference approaches to identify plasma proteins that have a potential causal impact on AAAs.</div></div><div><h3>Methods</h3><div>Causal inference was performed using two-sample Mendelian randomization (MR). For AAAs, we utilized recently published summary statistics from a multi-population genome-wide association meta-analysis including 39,221 individuals with and 1,086,107 individuals without AAAs from 14 cohorts. We used protein quantitative trait loci (protein quantitative trait loci) identified in two large-scale plasma-proteomics studies (deCODE and UKB-PPP) to generate genetic instruments. We tested 2783 plasma proteins for possible causal effects on AAAs using two-sample MR with inverse variance weighting with common sensitivity analyses.</div></div><div><h3>Results</h3><div>MR identified 90 plasma proteins associated with AAAs at a false discovery rate &lt;0.05, with 25 supported by colocalization analysis. Among those supported by both MR and colocalization were proteins such as PCSK9 (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.2-1.4; <em>P</em> &lt; 1e-10), LTBP4 (OR, 3.4; 95% CI, 2.6-4.6; <em>P</em> &lt; 1e-10), and COL6A3 (OR, 0.6; 95% CI, 0.5-0.7; <em>P</em> &lt; 1e-6). Gene Ontology analysis revealed enrichment of proteins (extracellular matrix; OR, 7.8; <em>P</em> &lt; 1e-4), some with maximal mRNA levels in aortic tissue. Bi-directional MR suggested plasma level changes were not caused by liability to AAA itself. Colocalization analysis showed that an aortic expression quantitative trait locus for COL6A3, and a splicing quantitative trait locus for LTBP4 colocalized with their respective plasma pQTLs and AAA signals.</div></div><div><h3>Conclusions</h3><div>Our results highlight proteins and pathways with potential causal effects on AAAs, providing a foundation for future functional experiments. These findings suggest a possible causal pathway whereby genetic variation affecting extracellular matrix proteins expressed in the aortic wall cause their levels to change in blood plasma, influencing development of AAAs.</div></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100290"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of platelets and antiplatelets medications on immune mediation","authors":"Leela Morena MD ,&nbsp;Isabella Ferlini Cieri MD ,&nbsp;Daniel Marconi Mendes PhD ,&nbsp;Sasha P. Suarez Ferreira MD ,&nbsp;Shiv Patel BS ,&nbsp;Samir Ghandour MD ,&nbsp;Maria Fernanda Andrade BS ,&nbsp;Mohit Manchella BS ,&nbsp;Adriana A. Rodriguez MD ,&nbsp;Henry Davies MBBS, MD, MRSC ,&nbsp;Shruti Sharma PhD ,&nbsp;Anahita Dua MD, MS, MBA","doi":"10.1016/j.jvssci.2024.100278","DOIUrl":"10.1016/j.jvssci.2024.100278","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the mechanisms through which platelets and antiplatelet therapies modulate the immune response and propose directions for future research in this field, with a particular emphasis on their impact on treatment efficacy and surgical outcomes.</div></div><div><h3>Methods</h3><div>A comprehensive review of recent studies investigating the role of platelets in immune modulation, specifically highlighting their involvement in pathogen recognition, leukocyte recruitment, and lymphocyte activation. Additionally, the review evaluates the impact of antiplatelet therapies, such as aspirin, P2Y12 inhibitors, and glycoprotein IIb/IIIa inhibitors, on immune responses.</div></div><div><h3>Results</h3><div>Recent studies have emphasized the critical role of platelets in immune-driven applications, namely, atherosclerosis, cancer, viral infections, and sepsis. These studies also suggest that antiplatelet therapies may alter immune responses. However, the precise mechanisms through which platelets and antiplatelet drugs influence immune responses, as well as their effects on post-treatment and surgical outcomes, are not yet fully elucidated.</div></div><div><h3>Conclusions</h3><div>Recent studies highlight the important role of platelets in immune processes, such as in atherosclerosis, cancer, viral infections, and sepsis, and suggest that antiplatelet therapies can influence immune responses. However, the exact mechanisms by which platelets and antiplatelet drugs modulate these responses remain unclear. This area presents valuable opportunities for future research to uncover these mechanisms, which could lead to novel therapeutic strategies and better clinical outcomes for patients.</div></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100278"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Piezo-type mechanosensitive ion channel component 1 (PIEZO1) is upregulated in peripheral arterial disease (PAD) and a novel murine PAD model","authors":"Fujie Zhao MD, PhD ,&nbsp;Feifei Li MD, PhD ,&nbsp;Farbod Sedaghati PhD ,&nbsp;Hai Dong PhD ,&nbsp;Sandeep Kumar PhD ,&nbsp;Dennis Gene Foster MD ,&nbsp;Jim Otto PhD ,&nbsp;Dana Giangiacomo BS ,&nbsp;Lucas H. Timmins PhD ,&nbsp;Maiko Sasaki MS, MPH ,&nbsp;Gloriani Sanchez Marrero BS ,&nbsp;Kyung In Baek PhD ,&nbsp;Michael Tu BS ,&nbsp;Sandra Peprah MD ,&nbsp;Xiangqin Cui PhD ,&nbsp;Jeffrey H. Lawson MD, PhD ,&nbsp;Rudolph L. Gleason PhD ,&nbsp;Hanjoong Jo PhD ,&nbsp;Luke Brewster MD, PhD","doi":"10.1016/j.jvssci.2025.100394","DOIUrl":"10.1016/j.jvssci.2025.100394","url":null,"abstract":"<div><h3>Objective</h3><div>The objectives of this work are to: define murine femoral artery stiffening with age and the modifiability of this process by exercise; impose peripheral arterial disease (PAD) hemodynamics on murine femoral arteries and to deliver focal atherosclerotic plaque to femoral arteries; and test piezo-type mechanosensitive ion channel component 1 (PIEZO1) expression in human and murine femoral arteries of PAD.</div></div><div><h3>Methods</h3><div>We used a running wheel to exercise young and old S129 mice and biomechanical testing to quantify changes in arterial stiffness. We created a novel partial femoral artery ligation (PFL) model to impose PAD hemodynamics via low wall shear stress (WSS) to create a flow-mediated model of arterial aging in femoral arteries. In vivo mechanics were defined with ultrasound. Ex vivo arteries underwent biaxial tests. Atherogenic conditions were induced using PCSK9 infection and a high-fat diet. Arterial remodeling and PIEZO1 expression were quantified by histology.</div></div><div><h3>Results</h3><div>Femoral arteries are naturally stiffer than carotid arteries; both stiffen further with aging, but exercise improved compliance in old femoral arteries. PFL imposed low WSS and stiffening, similar to that seen in aging. Under atherogenic conditions, PFL delivered focal atherosclerotic plaques in femoral arteries. Low WSS increased PIEZO1 expression in femoral arteries (∼1.8× in endothelial cells, ∼2.4× in smooth muscle cells, and ∼2.8× in macrophages). Human PAD arteries with high-grade stenosis validated increased PIEZO1 mRNA (∼1.83×).</div></div><div><h3>Conclusions</h3><div>Femoral artery mechanics differ significantly from the carotid artery but can be modified by exercise. This PFL model confers arterial stiffness, and under atherogenic conditions, delivers focal femoral atherosclerotic plaque. PIEZO1 expression increases in both PFL-treated mouse femoral arteries and human PAD arteries with severe stenosis, supporting this as a translational target for PAD.</div></div><div><h3>Clinical Relevance</h3><div>Peripheral artery disease (PAD) is the third most common atherosclerotic bed. PAD is associated with increased risk of limb loss and death, but the mechanisms driving site-specific arterial remodeling in PAD remain unclear. This work uniquely creates a model of PAD that incorporates arterial stiffening via aging and flow disturbances and inducing atherosclerotic plaque into the murine femoral artery. By comparing murine femoral arteries with PAD arteries, piezo-type mechanosensitive ion channel component 1 (PIEZO1) was discovered as key mediator linking PAD blood flow and stiffening to untoward changes in endothelial cells, smooth muscle cells, and macrophages within femoral arteries. Targeted modulation of PIEZO1 activity provide PAD-centric therapeutic strategies and help promote the vascular health, life, and limb outcomes in patients with PAD.</div></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100394"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145527958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}