JVS-vascular science最新文献

{"title":"Vascular adhesion molecule 1+ fibro-adipogenic progenitors mark fatty infiltration in chronic limb-threatening ischemia","authors":"Qunsheng Dai MD , Changxin Wan PhD , Yueyuan Xu PhD , Kaileen Fei MD , Lindsey A. Olivere MD , Hana Shafique BS, BA , Shaghayegh Sadeghmousavi MD , Camryn Johnson BS , Brianna Garrett MS , Leo Akers MS , Derek Peters MD, PhD , James Otto PhD , Christopher D. Kontos MD , Zhiceng Ji PhD , Yarui Diao PhD , Kevin W. Southerland MD","doi":"10.1016/j.jvssci.2025.100295","DOIUrl":"10.1016/j.jvssci.2025.100295","url":null,"abstract":"<div><h3>Background</h3><div>Skeletal muscle health and function are critical determinants of clinical outcomes in peripheral arterial disease. Chronic limb-threatening ischemia (CLTI), the most severe clinical manifestation of peripheral arterial disease, is associated with a 1-year amputation rate of 25%. In patients with CLTI, myosteatosis—the ectopic deposition of adipocytes—is independently associated with amputation. The mechanisms responsible for myosteatosis in patients with CLTI remain unknown. In this study, we aim to identify both the causal cellular population and the molecular mechanisms in patients with CLTI that promote myosteatosis.</div></div><div><h3>Methods</h3><div>To identify a candidate causal cell type and putative signaling axis that promotes myosteatosis, we performed single cell transcriptomic and chromatin accessibility profiling of ischemic muscle in a preclinical CLTI model. To assess the adipogenic potential for candidate subpopulations, we used an in vitro adipogenesis assay; myosteatosis was determined by Oil Red O (ORO), perilipin, and peroxisome proliferator-activated receptor gamma (PPAR-γ) staining. To determine the necessity of candidate transcriptional and epigenetic regulators, we used a small interfering RNA (siRNA). Finally, to assess the clinical significance of our findings, we used a publicly available human CLTI single cell RNA-sequencing dataset.</div></div><div><h3>Results</h3><div>Bulk-RNA sequencings and ORO staining reveal myosteatosis as a hallmark feature of the CLTI limb. Bioinformatic analyses reveal vascular adhesion molecule 1 (Vcam1)<sup>+</sup> fibro-adipogenic progenitors (FAPs) to be a proadipogenic cluster. Vcam1<sup>+</sup> FAPs display increased adipogenic potential compared with Vcam1<sup>−</sup> FAPs (ORO staining, <em>P</em> < .001; perilipin staining, <em>P</em> < .01; PPAR-γ staining, <em>P</em> < .05). Analyses of bulk and single cell RNA-sequencing datasets identify Sfrp1 as a regulator of Vcam1<sup>+</sup> FAP adipogenic differentiation. In vitro inhibition of Sfrp1 with a siRNA demonstrated impaired Vcam1<sup>+</sup> FAP adipogenic differentiation. Single cell ATAC sequencing identifies Nr3c1 as a candidate transcription factor that regulates Vcam1<sup>+</sup> FAP adipogenic differentiation. In vitro inhibition of Nr3c1 with a siRNA demonstrated decreased Sfrp1 expression (<em>P</em> < .01) and impaired adipogenic differentiation (ORO staining, <em>P</em> < .01; perilipin staining, <em>P</em> < .05; PPAR-γ, <em>P</em> < .001). Single cell transcriptomic profiling of paired nonischemic and ischemic muscle specimens from patients with CLTI displayed enriched gene expression of Vcam1 (<em>P</em> = 5.24e<sup>−166</sup>; log2FC = 0.89), Sfrp1 (<em>P</em> = 0; log2FC = 1.49) and Nr3c1 (<em>P</em> = .047; log2FC = 0.050) in ischemic CLTI muscle tissues. Altogether, these data reveal a candidate signaling axis, Nr3c1-Sfrp1, that regulates the differentiation of V","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100295"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007531","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":"Telmisartan modulates exercise responses in peripheral artery disease: Analyses of skeletal muscle from the TELEX Trial","authors":"Kate Kosmac PhD ,&nbsp;Jai K. Joshi BS ,&nbsp;Mary M. McDermott MD ,&nbsp;Jada C. Stewart BS ,&nbsp;Dongxue Zhang MS ,&nbsp;Shujun Xu MS ,&nbsp;Karen J. Ho MD ,&nbsp;Robert Sufit MD ,&nbsp;Luigi Ferrucci MD ,&nbsp;Charlotte A. Peterson PhD ,&nbsp;Ahmed Ismaeel PhD","doi":"10.1016/j.jvssci.2025.100294","DOIUrl":"10.1016/j.jvssci.2025.100294","url":null,"abstract":"<div><h3>Objective</h3><div>In people with peripheral artery disease (PAD), the Telmisartan Plus Exercise to Improve Functioning in Peripheral Artery Disease (TELEX) randomized clinical trial tested whether telmisartan (TEL), with or without exercise, significantly improved 6-minute walk distance at 6-month follow-up, compared with placebo (PLA). This study investigated the effects of TEL on exploratory muscle biopsy outcomes of muscle cellular characteristics (myofiber size, satellite cell content, capillary density, extracellular matrix, and collagen area) and molecular characteristics (cell-specific transcriptomics) in people undergoing supervised exercise in the TELEX Trial.</div></div><div><h3>Methods</h3><div>Baseline and 6-month follow-up muscle biopsies were obtained from 13 participants with PAD in the TELEX trial randomized to exercise + TEL (n = 6) or exercise + PLA (n = 7). Immunohistochemistry was used to measure muscle cellular characteristics, and the GeoMx digital spatial profiling system was used for transcriptomic analyses of alpha-smooth muscle actin (α-SMA)-positive and α-SMA-negative cells (primarily myofibers).</div></div><div><h3>Results</h3><div>Compared with exercise + PLA, exercise + TEL increased mean myofiber cross-sectional area (+2175 μm²; 95% confidence interval, −266 to 4615; <em>P</em> = .04) and the number of satellite cells associated with type II myofibers (+17; 95% confidence interval, −1 to 35; <em>P</em> = .03). In α-SMA-negative cells, exercise + TEL upregulated peroxisome proliferator-activated receptor gamma activation-related pathways, including nitric oxide-cyclic guanosine monophosphate-protein kinase G signaling (<em>P</em> = .008), and fatty acid oxidation (<em>P</em> = .011). Exercise + TEL also reduced myostatin expression relative to exercise + PLA in α-SMA-negative cells (Log2fold-change = −1.24; false discovery rate = 0.010).</div></div><div><h3>Conclusions</h3><div>TEL may influence the effects of exercise on muscle in individuals with PAD by reducing myostatin expression, increasing myofiber size, and increasing activation of peroxisome proliferator-activated receptor gamma. Further study is needed to confirm these findings.</div></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100294"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144828098","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":"Evaluation of sex-based differences in below-the-knee plaque histology in patients who underwent amputation for chronic limb-threatening ischemia","authors":"Fouzul Kansul ,&nbsp;Deborah Vela MD ,&nbsp;Judit Csore MD ,&nbsp;Bright Benfor MD ,&nbsp;Sasha Suarez MD ,&nbsp;Anahita Dua MD, MBA, MSC ,&nbsp;Trisha L. Roy MD, PhD","doi":"10.1016/j.jvssci.2024.100269","DOIUrl":"10.1016/j.jvssci.2024.100269","url":null,"abstract":"<div><h3>Objective</h3><div>With the growing incidence of peripheral arterial disease (PAD) and the historic under-representation of female patients in cardiovascular trials, a comprehensive evaluation of sex-based variances in PAD presentation and treatment outcomes is needed. This study aims to evaluate sex-based differences in the vessel wall characteristics of patients who underwent amputation owing to critical limb-threatening ischemia to optimize personalized treatment planning and aid in the selection of endovascular devices for PAD patients.</div></div><div><h3>Methods</h3><div>A total of 35 lower limbs were collected from 34 patients with end-stage PAD undergoing major amputation. We selected, harvested, and cross-sectioned at 3- to 4-mm intervals 163 diseased below-the-knee arterial segments resulting in 1260 arterial rings. Histological analyses were conducted on each individual ring and later summarized by arterial segment.</div></div><div><h3>Results</h3><div>Male and female patients were remarkably similar across multiple plaque characteristics, including degree of stenosis, calcification severity and localization, and atherosclerotic patterns. A significant sex-based difference was noted in the presence of luminal thrombus, which was more prevalent in females (38.7% vs 25.0%; <em>P</em> = .016). Histopathological differences were noted between popliteal and tibial lesions, with popliteal segments demonstrating increased chronic total occlusion presence and atherosclerosis, whereas severe calcification occurred more often in tibial segments. A sex-based evaluation of the popliteal segments showed increased calcification (60.71% vs 28.0%; <em>P</em> = .003) and atherosclerosis (96.4% vs 73.0%; <em>P</em> = .028) in males compared with females.</div></div><div><h3>Conclusions</h3><div>Differences in the degree of calcification, incidence of atherosclerosis, and presence of luminal thrombus may pose important clinical implications for antiplatelet and anticoagulation regimen choice and guide treatment options. Further studies are warranted to evaluate the impact of these differences on outcomes of endovascular procedures.</div></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100269"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082227","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":"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":"Enhanced antimicrobial efficacy by impregnation of vascular grafts with nanocolloidal silver","authors":"Karin Lindén MD ,&nbsp;Philipp Seeger MD ,&nbsp;Samira Weisselberg PhD ,&nbsp;Eike Sebastian Debus MD","doi":"10.1016/j.jvssci.2025.100286","DOIUrl":"10.1016/j.jvssci.2025.100286","url":null,"abstract":"<div><h3>Objective</h3><div>This in vitro study aims to evaluate any additional antimicrobial efficacy by impregnating nanocolloidal silver on commercially available vascular grafts, to compare the results with precoated silver grafts, and to test the feasibility of the procedure.</div></div><div><h3>Methods</h3><div>Vascular grafts from a prosthetic graft material of polyester (polyethylene terephthalate, Dacron) and from a xenograft (bovine pericardium) were sprayed with a nanocolloidal silver solution on both sides of the grafts and left to vaporize for 10 minutes. Thereafter, the grafts were cut into 1 × 1 cm² graft units (GUs) and incubated at 37°C for 1 or 24 hours, respectively, with a 10⁶ bacteria/mL solution from four bacterial strains: <em>Pseudomonas aeruginosa</em>, <em>Staphylococcus epidermidis</em>, <em>Escherichia coli</em>, and methicillin-sensitive <em>Staphylococcus aureus.</em> In addition, the untreated grafts from polyester and bovine pericardium, as well as the precoated silver grafts, were cut and incubated analogously, resulting in 5 groups of 80 GUs each (n = 400). After incubation, each GU was washed and sonicated and samples from each sonication fluid were plated on separate Müller-Hinton Agar (MH) plates. These were incubated at 37°C and CFU were counted after 24 hours.</div></div><div><h3>Results</h3><div>Grafts impregnated with nanocolloidal silver spray demonstrated a statistically significant decrease in detected adhering bacteria compared to their controls, both after 1 hour and 24 hours of incubation (<em>P</em>_adj &lt; .001 to .006). The only nonsignificant result was recorded for polyester after 1 hour of incubation with <em>Pseudomonas aeruginosa</em> (<em>P</em>_adj = .721). In addition, no significant difference between the impregnated grafts and the precoated silver graft was demonstrated after 24 hours of incubation.</div></div><div><h3>Conclusions</h3><div>Impregnating vascular grafts from polyester and bovine pericardium with a nanocolloidal silver spray, before inoculation with a bacterial suspension, significantly reduced bacterial colonization on the grafts. The procedure proved feasible and should be tested further in in vitro and in vivo trials.</div></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100286"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138836","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":"Sox17 mediates venous adaptive remodeling after arteriovenous fistula creation","authors":"Yukihiko Aoyagi MD ,&nbsp;Andrew W. Schwartz BS ,&nbsp;Zhuo Li MD, PhD ,&nbsp;Hualong Bai MD, PhD ,&nbsp;Bryan Ho MD ,&nbsp;Cayetana Lazcano-Etchebarne BS ,&nbsp;Luis Gonzalez PhD ,&nbsp;Yuichi Ohashi MD ,&nbsp;Masaki Kano MD ,&nbsp;Bogdan Yatsula PhD ,&nbsp;Cassius Iyad Ochoa Chaar MD, MPH, MS ,&nbsp;Kathleen Martin PhD ,&nbsp;Roberto Vazquez-Padron PhD ,&nbsp;Guohao Dai PhD ,&nbsp;Alan Dardik MD, PhD","doi":"10.1016/j.jvssci.2025.100392","DOIUrl":"10.1016/j.jvssci.2025.100392","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;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 &lt;em&gt;t&lt;/em&gt; tests were used for statistical analyses.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Sox17 was significantly elevated in mature human AVF compared with control veins (&lt;em&gt;P&lt;/em&gt; = .02) and in mature human AVF compared with failed human AVF (&lt;em&gt;P&lt;/em&gt; = .04). In the mouse AVF, Sox17 expression was also significantly upregulated compared with sham-operated mice (&lt;em&gt;P&lt;/em&gt; = .0012 in male mice; &lt;em&gt;P&lt;/em&gt; = .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 (&lt;em&gt;P&lt;/em&gt; = .001) and thinner intima-media layers relative to control AVF (&lt;em&gt;P&lt;/em&gt; = .015). Sox17 knockdown mice had decreased JAG1 expression (&lt;em&gt;P&lt;/em&gt; = .008) and decreased smooth muscle cell proliferation (&lt;em&gt;P&lt;/em&gt; = .03) on day 7.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Clinical Relevance&lt;/h3&gt;&lt;div&gt;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":"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":"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":"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}