Adham N. Abou Ali MD , Patrick Cherfan MD , Ashraf G. Taha MD , Michel S. Makaroun MD , Yingze Zhang PhD , Xucai X. Chen PhD , Flordeliza S. Villanueva MD , Rabih A. Chaer MD
{"title":"Contrast-enhanced ultrasound microbubble uptake and abnormal plasma biomarkers are seen in patients with abdominal aortic aneurysms","authors":"Adham N. Abou Ali MD , Patrick Cherfan MD , Ashraf G. Taha MD , Michel S. Makaroun MD , Yingze Zhang PhD , Xucai X. Chen PhD , Flordeliza S. Villanueva MD , 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}
Baqir Kedwai BHSc , Joshua Geiger MD , Sam Najjar BS , Joel Kruger MD , Michael Richards PhD , Chung Yeh BS , Mary Dennehy BS , Michael Stoner MD , Doran Mix MD
{"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 , Joshua Geiger MD , Sam Najjar BS , Joel Kruger MD , Michael Richards PhD , Chung Yeh BS , Mary Dennehy BS , Michael Stoner MD , Doran Mix MD","doi":"10.1016/j.jvssci.2025.100287","DOIUrl":"10.1016/j.jvssci.2025.100287","url":null,"abstract":"<div><h3>Background</h3><div>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 (<span><math><mrow><mover><msub><mi>ε</mi><mrow><mi>ρ</mi><mo>+</mo></mrow></msub><mo>¯</mo></mover></mrow></math></span>/PP) of an idealized 3D-printed abdominal aortic aneurysm model.</div></div><div><h3>Methods</h3><div>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 (<span><math><mrow><mover><msub><mi>ε</mi><mrow><mi>ρ</mi><mo>+</mo></mrow></msub><mo>¯</mo></mover></mrow></math></span>/PP).</div></div><div><h3>Results</h3><div>In the 100% packing condition, <span><math><mrow><mover><msub><mi>ε</mi><mrow><mi>ρ</mi><mo>+</mo></mrow></msub><mo>¯</mo></mover></mrow></math></span>/PP was +113% above baseline at 15 minutes. After sequential deployment to 400%, the <span><math><mrow><mover><msub><mi>ε</mi><mrow><mi>ρ</mi><mo>+</mo></mrow></msub><mo>¯</mo></mover></mrow></math></span>/PP trended down to +43% above baseline. Immediate packing was associated with a greater <span><math><mrow><mover><msub><mi>ε</mi><mrow><mi>ρ</mi><mo>+</mo></mrow></msub><mo>¯</mo></mover></mrow></math></span>/PP reduction than sequential packing. When packed immediately to 400%, the <span><math><mrow><mover><msub><mi>ε</mi><mrow><mi>ρ</mi><mo>+</mo></mrow></msub><mo>¯</mo></mover></mrow></math></span>/PP was −6.7% below baseline.</div></div><div><h3>Conclusions</h3><div>These modeling data suggest that an immediate deployment strategy and higher plug packing volumes are associated with lower <span><math><mrow><mover><msub><mi>ε</mi><mrow><mi>ρ</mi><mo>+</mo></mrow></msub><mo>¯</mo></mover></mrow></math></span>/PP, which has been associated with decreased sac growth rates.</div></div><div><h3>Clinical Relevance</h3><div>The present findings suggest that rapid, high-volume filling of IMPEDE-FX embolization plugs results in a reduction in wall <span><math><mrow><mover><msub><mi>ε</mi><mrow><mi>ρ</mi><mo>+</mo></mrow></msub><mo>¯</mo></mover></mrow></math></span>/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 <span><math><mrow><mover><msub><mi>ε</mi><mrow><mi>ρ</mi><mo>+</mo>","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}
Karin Lindén MD , Philipp Seeger MD , Samira Weisselberg PhD , Eike Sebastian Debus MD
{"title":"Enhanced antimicrobial efficacy by impregnation of vascular grafts with nanocolloidal silver","authors":"Karin Lindén MD , Philipp Seeger MD , Samira Weisselberg PhD , 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 cm<sup>2</sup> graft units (GUs) and incubated at 37°C for 1 or 24 hours, respectively, with a 10<sup>6</sup> 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><sub>adj</sub> < .001 to .006). The only nonsignificant result was recorded for polyester after 1 hour of incubation with <em>Pseudomonas aeruginosa</em> (<em>P</em><sub>adj</sub> = .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}
Sean M. Carr PhD, Ottis Scrivner PhD, Katherine Elizabeth Hekman MD, PhD
{"title":"Narrative review of endothelial cell metabolism and aberrations in atherosclerosis and peripheral artery disease","authors":"Sean M. Carr PhD, Ottis Scrivner PhD, 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}
Marcos Vinícius Melo de Oliveira MD, PhD , Alexandre Malta Brandão MD, PhD , Gina Camillo Rocha Silvestre BS , Alexandre Queiroz Silva BS , Michele Alberto Marques BS , Marcia Martins Reis PhD , Maria de Lourdes Higuchi MD, PhD , Erasmo Simão da Silva MD, PhD
{"title":"Comparative analysis between abdominal aortic aneurysm and popliteal artery aneurysm","authors":"Marcos Vinícius Melo de Oliveira MD, PhD , Alexandre Malta Brandão MD, PhD , Gina Camillo Rocha Silvestre BS , Alexandre Queiroz Silva BS , Michele Alberto Marques BS , Marcia Martins Reis PhD , Maria de Lourdes Higuchi MD, PhD , 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/m<sup>2</sup> vs 9.95 N/m<sup>2</sup>; <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}
Blair E. Warren MD, MSCS , Kong-Teng Tan MD , Dheeraj K. Rajan MD , Miranda Witheford MD, PhD , Sean Crawford MD, MSc , Arash Jaberi MD, MEd , Sebastian Mafeld MBBS
{"title":"Moving away from metal: Step toward the future with bioresorbable vascular scaffolds and novel antiproliferative agents","authors":"Blair E. Warren MD, MSCS , Kong-Teng Tan MD , Dheeraj K. Rajan MD , Miranda Witheford MD, PhD , Sean Crawford MD, MSc , Arash Jaberi MD, MEd , Sebastian Mafeld MBBS","doi":"10.1016/j.jvssci.2024.100277","DOIUrl":"10.1016/j.jvssci.2024.100277","url":null,"abstract":"<div><h3>Background</h3><div>Peripheral arterial disease (PAD) is a common source of morbidity and mortality globally and is expected to raise increase in prevalence. Many endovascular techniques exist to manage PAD; however, there remains room for improvement, especially as it relates to below-the-knee vessels. Recent evidence and devices are leading to a resurgence of interest in bioresorbable vascular scaffolds and the -limus family of antiproliferative drugs in the PAD treatment space.</div></div><div><h3>Methods</h3><div>This nonsystematic review examines emerging technology for treatment of PAD with a specific focus on below-the-knee vessels and bioresorbable vascular scaffolds. Additional emerging and early technology such as novel delivery platforms are also briefly discussed with directions of future research highlighted.</div></div><div><h3>Results</h3><div>Bioresorbable vascular scaffold biomechanics and history are highlighted. Foundational knowledge of antiproliferative agents and evolving agents in peripheral vascular disease are also described.</div></div><div><h3>Conclusions</h3><div>Bioresorbable vascular scaffolds are an additional endovascular tool for the treatment of peripheral vascular disease. The integration with an antiproliferative agent may result in improved patency and performance; however, there is a paucity of data in the literature at present.</div></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100277"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143139171","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}
Leela Morena MD , Isabella Ferlini Cieri MD , Daniel Marconi Mendes PhD , Sasha P. Suarez Ferreira MD , Shiv Patel BS , Samir Ghandour MD , Maria Fernanda Andrade BS , Mohit Manchella BS , Adriana A. Rodriguez MD , Henry Davies MBBS, MD, MRSC , Shruti Sharma PhD , Anahita Dua MD, MS, MBA
{"title":"The impact of platelets and antiplatelets medications on immune mediation","authors":"Leela Morena MD , Isabella Ferlini Cieri MD , Daniel Marconi Mendes PhD , Sasha P. Suarez Ferreira MD , Shiv Patel BS , Samir Ghandour MD , Maria Fernanda Andrade BS , Mohit Manchella BS , Adriana A. Rodriguez MD , Henry Davies MBBS, MD, MRSC , Shruti Sharma PhD , 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}
Paul Cyréus MSc , Katarina Wadén MD , Sofie Hellberg MSc , Otto Bergman PhD , Mariette Lengquist MSc , Eva Karlöf MD, PhD , Andrew Buckler PhD , Ljubica Matic PhD , Joy Roy MD, PhD , David Marlevi PhD , Melody Chemaly PhD , Ulf Hedin MD, PhD
{"title":"Atherosclerotic plaque instability in symptomatic non-significant carotid stenoses","authors":"Paul Cyréus MSc , Katarina Wadén MD , Sofie Hellberg MSc , Otto Bergman PhD , Mariette Lengquist MSc , Eva Karlöf MD, PhD , Andrew Buckler PhD , Ljubica Matic PhD , Joy Roy MD, PhD , David Marlevi PhD , Melody Chemaly PhD , Ulf Hedin MD, PhD","doi":"10.1016/j.jvssci.2025.100280","DOIUrl":"10.1016/j.jvssci.2025.100280","url":null,"abstract":"<div><h3>Objective</h3><div>Carotid endarterectomy for symptomatic carotid stenosis is recommended for patients with >70% stenosis, but not in those with <50%. Because non-significant, low-degree stenoses may still cause strokes, refined risk stratification is necessary, which could be improved by assessing biological features of plaque instability. To challenge risk-stratification based on luminal narrowing, we compared biological features of carotid plaques from symptomatic patients with low-degree (<50%) vs high-degree (>70%) stenosis and explored potential mechanisms behind plaque instability in low-degree stenoses.</div></div><div><h3>Methods</h3><div>Endarterectomy specimens were taken from symptomatic patients with high-degree (n = 204) and low-degree (n = 34) stenosis, all part of the Biobank of Karolinska Endarterectomies. Patient demographics, image-derived plaque morphology, and gene expression analyses of extracted lesions were used for comparisons. Plaque biology was assessed by transcriptomics using dimensionality reduction, differential gene expression, and gene-set enrichment analyses. Immunohistochemistry was used to study proteins corresponding to upregulated genes.</div></div><div><h3>Results</h3><div>The demographics of the two groups were statistically similar. Calcification, lipid-rich necrotic core, intraplaque hemorrhage, plaque burden, and fibrous cap thickness were similar in both groups, whereas the sum of lipid-rich necrotic core and intraplaque hemorrhage was higher (<em>P</em> = .033) in the high-degree stenosis group. Dimensionality reduction analysis indicated poor clustering separation of plaque gene expression in low-compared with high-degree stenosis lesions, whereas differential gene expression showed upregulation of hypoxia-inducible factor 3A (log<sub>2</sub> fold change, 0.7212; <em>P</em> = .0003), and gene-set enrichment analyses identified pathways related to tissue hypoxia and angiogenesis in low-degree stenoses. Hypoxia-inducible factor 3-alpha protein was associated with smooth muscle cells in neo-vascularized plaque regions.</div></div><div><h3>Conclusions</h3><div>Plaques from symptomatic patients with non-significant low-degree carotid stenoses showed morphologic and biological features of atherosclerotic plaque instability that were comparable to plaques from patients with high-degree stenoses, emphasizing the need for improved stroke risk stratification for intervention in all patients with symptomatic carotid stenosis irrespective of luminal narrowing. An increased expression of hypoxia-inducible factor 3A in low-degree stenotic lesions suggested mechanisms of plaque instability associated with tissue hypoxia and plaque angiogenesis, but the exact role of hypoxia-inducible factor 3A in this process remains to be determined.</div></div><div><h3>Clinical relevance</h3><div>Carotid plaques from symptomatic patients with <50% stenosis show morphologic and biological features of plaque ","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100280"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403650","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}
Samuel Khodursky PhD , Shuai Yuan PhD , Joshua M. Spin MD, PhD , Philip S. Tsao PhD , Michael G. Levin MD , Scott M. Damrauer MD
{"title":"Plasma proteome-wide Mendelian randomization reveals the association of extracellular matrix proteins with abdominal aortic aneurysm","authors":"Samuel Khodursky PhD , Shuai Yuan PhD , Joshua M. Spin MD, PhD , Philip S. Tsao PhD , Michael G. Levin MD , 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 <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> < 1e-10), LTBP4 (OR, 3.4; 95% CI, 2.6-4.6; <em>P</em> < 1e-10), and COL6A3 (OR, 0.6; 95% CI, 0.5-0.7; <em>P</em> < 1e-6). Gene Ontology analysis revealed enrichment of proteins (extracellular matrix; OR, 7.8; <em>P</em> < 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":"Toll-Like Receptor 4, a potential therapeutic target of lower limb ischemic myopathy that raises further questions","authors":"Ali H. Hakim, Ulf Hedin","doi":"10.1016/j.jvssci.2024.100195","DOIUrl":"https://doi.org/10.1016/j.jvssci.2024.100195","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"60 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139824700","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}