Pub Date : 2026-01-01DOI: 10.1016/j.jvssci.2025.100399
Yae Hyun Rhee MD , Joshua M. Spin MD, PhD , Philip S. Tsao PhD
Objective
Abdominal aortic aneurysms (AAAs) arise through complex pathogenesis, and good methods of risk stratification have proved elusive. Further, the lack of medical options short of surgery for treatment, and the requirement for dedicated imaging for identification, result in delayed diagnosis and hamper patient outcomes. Application of circulating biomarkers to effectively assess disease presence and predict progression would improve clinical management and support patient well-being. Exploration for suitable circulating biomarkers of AAAs is still very much in process; however, no disease-specific biomarker has yet been established for effective diagnosis and prognosis. This review aims to contribute enhanced tools for utilizing biomarkers for risk stratification and management of AAA disease.
Methods
Utilizing MEDLINE/PubMed, we summarize 44 recent publications covering circulating AAA biomarkers. The biomarkers were categorized and tiered into six subgroups by study design, with prospective studies tiered higher than retrospective observational studies. The classification system separately describes a list of post-interventional monitoring biomarkers. Part of the review also deals with recent approaches to identifying potential AAA biomarkers by genetic inference.
Results
Forty individual circulating biomarkers, two plasma protein panels (consisting of 9 or 7 proteins), one plasma-multiomic study, and two micro-RNA (miR) panels revealed correlations to AAA disease risk. Among those, many have already been established as biomarkers for other cardiovascular diseases, meaning feasibility has been proven but disease specificity is lacking.
Conclusions
Multiple circulating proteins and miRs have been investigated for their utility as AAA-specific diagnostic or prognostic biomarkers. This work may ultimately identify not only novel AAA biomarkers that are specific for cell type, proteins, metabolites, genetic polymorphisms, and miRNA, but permit framing of comprehensive networks of disease-participating molecules. More robust data with higher disease sensitivity and specificity are needed, along with more multi-centered longitudinal clinical studies with large sample sizes.
{"title":"A narrative review of recent literature of circulating biomarkers of abdominal aortic aneurysm","authors":"Yae Hyun Rhee MD , Joshua M. Spin MD, PhD , Philip S. Tsao PhD","doi":"10.1016/j.jvssci.2025.100399","DOIUrl":"10.1016/j.jvssci.2025.100399","url":null,"abstract":"<div><h3>Objective</h3><div>Abdominal aortic aneurysms (AAAs) arise through complex pathogenesis, and good methods of risk stratification have proved elusive. Further, the lack of medical options short of surgery for treatment, and the requirement for dedicated imaging for identification, result in delayed diagnosis and hamper patient outcomes. Application of circulating biomarkers to effectively assess disease presence and predict progression would improve clinical management and support patient well-being. Exploration for suitable circulating biomarkers of AAAs is still very much in process; however, no disease-specific biomarker has yet been established for effective diagnosis and prognosis. This review aims to contribute enhanced tools for utilizing biomarkers for risk stratification and management of AAA disease.</div></div><div><h3>Methods</h3><div>Utilizing MEDLINE/PubMed, we summarize 44 recent publications covering circulating AAA biomarkers. The biomarkers were categorized and tiered into six subgroups by study design, with prospective studies tiered higher than retrospective observational studies. The classification system separately describes a list of post-interventional monitoring biomarkers. Part of the review also deals with recent approaches to identifying potential AAA biomarkers by genetic inference.</div></div><div><h3>Results</h3><div>Forty individual circulating biomarkers, two plasma protein panels (consisting of 9 or 7 proteins), one plasma-multiomic study, and two micro-RNA (miR) panels revealed correlations to AAA disease risk. Among those, many have already been established as biomarkers for other cardiovascular diseases, meaning feasibility has been proven but disease specificity is lacking.</div></div><div><h3>Conclusions</h3><div>Multiple circulating proteins and miRs have been investigated for their utility as AAA-specific diagnostic or prognostic biomarkers. This work may ultimately identify not only novel AAA biomarkers that are specific for cell type, proteins, metabolites, genetic polymorphisms, and miRNA, but permit framing of comprehensive networks of disease-participating molecules. More robust data with higher disease sensitivity and specificity are needed, along with more multi-centered longitudinal clinical studies with large sample sizes.</div></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"7 ","pages":"Article 100399"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023639","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}
Pub Date : 2026-01-01DOI: 10.1016/j.jvssci.2025.100404
Camilo Polania Sandoval MD , James F. Meschia MD , Mercedes Prudencio PhD , Tania Gendron PhD , Christopher Jacobs MD , Richard D. Beegle MD , Sukhwinder J.S. Sandhu MD , Kiran K. Mangalaparthi PhD , Jaeyun Sung PhD , Xiaowei Zhao PhD , Aziza Nassar MD, MPH, MBA , Houssam Farres MD , Leonard Petrucelli PhD , Akhilesh Pandey MD, PhD , Young Erben MD
<div><h3>Background</h3><div>Carotid plaque vulnerability is a current feature that aids in the decision-making for ischemic stroke risk. Proteomic analysis of plaque tissue can reveal molecular indicators of instability that complement imaging findings. We sought to identify a proteomic signature distinguishing vulnerable from stable carotid plaques in patients undergoing endarterectomy, with the aim of uncovering candidate biomarkers for potential diagnostic and therapeutic targets.</div></div><div><h3>Methods</h3><div>Twenty-eight carotid plaque specimens were collected from 27 patients (including 1 patient with bilateral endarterectomy). Samples were classified as vulnerable (n = 14) or nonvulnerable (n = 14) based on preoperative magnetic resonance angiography with vessel wall imaging. A tandem mass tag-based multiplexing strategy followed by mass spectrometric analysis was used to profile the proteomes of all samples. Normalized and log<sub>2</sub>-transformed protein intensities were compared using two-sample <em>t</em> tests with unequal variances, and <em>P</em> values were adjusted for multiple testing with the Benjamini-Hochberg method to obtain false discovery rate <em>q</em> values. Proteins with a <em>q</em> value of ≤0.25 were designated high-confidence candidates, and those with a <em>P</em> value of <.05 but a <em>q</em> value of >0.25 were considered exploratory.</div></div><div><h3>Results</h3><div>From 3267 proteins identified, 398 reached nominal significance (<em>P</em> < .05). From those, 29 reached at least log<sub>2</sub>(fold-change) of +1, whereas 3 of −1 log<sub>2</sub>(fold change), yielding a total of 32 proteins. Fifteen were significant for a <em>q</em> value ≤0.25. All were upregulated in vulnerable lesions and these included: matrix-degrading enzymes (matrix metalloproteinase [MMP]7, MMP9, MMP1, and ADAM-like decysin-1), neutrophil-derived effectors (azurocidin, cathelicidin antimicrobial peptide, lactotransferrin, and myeloperoxidase), inflammatory regulators (interleukin-1 receptor antagonist and interleukin-4-induced protein), glycolytic enzymes (hexokinase-3 and hexokinase-2), and lipid-handling proteins (lipoprotein-associated phospholipase A<sub>2</sub>, apolipoprotein B, and paraoxonase-1). An additional 17 exploratory proteins showed nominal significance (<em>P</em> < .05, <em>q</em> > 0.25) with at least log<sub>2</sub>(fold-change) of 1, and 366 proteins with nominal significance but with a log<sub>2</sub>(fold-change) of <1.</div></div><div><h3>Conclusions</h3><div>Our proteomic profiling delineates a robust vulnerability signature marked by enhanced proteolysis, neutrophil activation, inflammatory signaling, metabolic reprogramming, and lipid dysregulation. High-confidence proteins emerged as tissue biomarkers of plaque instability. Validating their association with future cerebrovascular events is the next step toward clinically actionable stroke prediction. Exploratory candidates w
{"title":"Proteomic signatures of carotid plaque vulnerability: Proteolysis, inflammation, metabolic reprogramming, and lipid dysregulation","authors":"Camilo Polania Sandoval MD , James F. Meschia MD , Mercedes Prudencio PhD , Tania Gendron PhD , Christopher Jacobs MD , Richard D. Beegle MD , Sukhwinder J.S. Sandhu MD , Kiran K. Mangalaparthi PhD , Jaeyun Sung PhD , Xiaowei Zhao PhD , Aziza Nassar MD, MPH, MBA , Houssam Farres MD , Leonard Petrucelli PhD , Akhilesh Pandey MD, PhD , Young Erben MD","doi":"10.1016/j.jvssci.2025.100404","DOIUrl":"10.1016/j.jvssci.2025.100404","url":null,"abstract":"<div><h3>Background</h3><div>Carotid plaque vulnerability is a current feature that aids in the decision-making for ischemic stroke risk. Proteomic analysis of plaque tissue can reveal molecular indicators of instability that complement imaging findings. We sought to identify a proteomic signature distinguishing vulnerable from stable carotid plaques in patients undergoing endarterectomy, with the aim of uncovering candidate biomarkers for potential diagnostic and therapeutic targets.</div></div><div><h3>Methods</h3><div>Twenty-eight carotid plaque specimens were collected from 27 patients (including 1 patient with bilateral endarterectomy). Samples were classified as vulnerable (n = 14) or nonvulnerable (n = 14) based on preoperative magnetic resonance angiography with vessel wall imaging. A tandem mass tag-based multiplexing strategy followed by mass spectrometric analysis was used to profile the proteomes of all samples. Normalized and log<sub>2</sub>-transformed protein intensities were compared using two-sample <em>t</em> tests with unequal variances, and <em>P</em> values were adjusted for multiple testing with the Benjamini-Hochberg method to obtain false discovery rate <em>q</em> values. Proteins with a <em>q</em> value of ≤0.25 were designated high-confidence candidates, and those with a <em>P</em> value of <.05 but a <em>q</em> value of >0.25 were considered exploratory.</div></div><div><h3>Results</h3><div>From 3267 proteins identified, 398 reached nominal significance (<em>P</em> < .05). From those, 29 reached at least log<sub>2</sub>(fold-change) of +1, whereas 3 of −1 log<sub>2</sub>(fold change), yielding a total of 32 proteins. Fifteen were significant for a <em>q</em> value ≤0.25. All were upregulated in vulnerable lesions and these included: matrix-degrading enzymes (matrix metalloproteinase [MMP]7, MMP9, MMP1, and ADAM-like decysin-1), neutrophil-derived effectors (azurocidin, cathelicidin antimicrobial peptide, lactotransferrin, and myeloperoxidase), inflammatory regulators (interleukin-1 receptor antagonist and interleukin-4-induced protein), glycolytic enzymes (hexokinase-3 and hexokinase-2), and lipid-handling proteins (lipoprotein-associated phospholipase A<sub>2</sub>, apolipoprotein B, and paraoxonase-1). An additional 17 exploratory proteins showed nominal significance (<em>P</em> < .05, <em>q</em> > 0.25) with at least log<sub>2</sub>(fold-change) of 1, and 366 proteins with nominal significance but with a log<sub>2</sub>(fold-change) of <1.</div></div><div><h3>Conclusions</h3><div>Our proteomic profiling delineates a robust vulnerability signature marked by enhanced proteolysis, neutrophil activation, inflammatory signaling, metabolic reprogramming, and lipid dysregulation. High-confidence proteins emerged as tissue biomarkers of plaque instability. Validating their association with future cerebrovascular events is the next step toward clinically actionable stroke prediction. Exploratory candidates w","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"7 ","pages":"Article 100404"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078304","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}
Pub Date : 2026-01-01DOI: 10.1016/j.jvssci.2025.100405
Gözde Tekin MD , Özge Çevik PhD , Şule Çetinel MD , Göksel Şener PhD , Mehmet Kızılay MD
Objective
Oxidative stress and inflammation are widely recognized as central mechanisms in the pathogenesis of abdominal aortic aneurysm. This study sought to examine the potential protective properties of montelukast in a rat model of aortic aneurysm.
Methods
Male Sprague-Dawley rats were randomly allocated into three experimental groups. Abdominal aortic aneurysm was induced using the calcium chloride (CaCl2) model, in which gauze soaked in 0.5 M CaCl2 was placed directly onto the adventitial surface of the infrarenal abdominal aorta for 15 minutes. After induction, the treatment group received daily intraperitoneal injections of montelukast (10 mg/kg) for 4 consecutive weeks. At the study end point, animals were euthanized, and infrarenal aortic tissues were harvested for biochemical and histological evaluations. Measured parameters included matrix metalloproteinase (MMP)-2 and MMP-9 expression, myeloperoxidase (MPO) activity, and 8-hydroxy-2′-deoxyguanosine levels. Antioxidant capacity was assessed through superoxide dismutase (SOD) activity assays. Histopathological examinations were performed, and statistical analysis was conducted using GraphPad Prism v.5.
Results
Exposure to CaCl2 triggered pronounced oxidative injury and inflammation, as evidenced by elevated 8-hydroxy-2′-deoxyguanosine levels, increased MPO activity, reduced SOD activity, and upregulated MMP-2 and MMP-9 expression. Montelukast administration markedly attenuated these changes, normalizing oxidative and inflammatory markers while improving histopathological architecture.
Conclusions
Montelukast effectively counteracted CaCl2-induced aortic damage. The protective effects of montelukast appear to be mediated through suppression of MMP activity, restoration of SOD levels, and reduction of MPO-driven oxidative injury. By mitigating both inflammatory and oxidative mechanisms, montelukast contributes to the preservation of aortic wall structure.
Clinical Relevance
Abdominal aortic aneurysm remains a major vascular disorder without an effective pharmacological therapy to slow its progression. In this experimental study, montelukast, a leukotriene receptor antagonist widely used in asthma, attenuated abdominal aortic aneurysm formation in rats and was associated with increased superoxide dismutase activity, reduced myeloperoxidase levels, and suppressed matrix metalloproteinase activation. These combined antioxidant, anti-inflammatory, and matrix-stabilizing effects preserved aortic wall integrity. Given montelukast's established safety and clinical availability, these findings support its potential for future clinical investigation as a pharmacological approach to limit aneurysm progression.
{"title":"Montelukast attenuates abdominal aortic aneurysm in rats: Anti-inflammatory and antioxidant effects","authors":"Gözde Tekin MD , Özge Çevik PhD , Şule Çetinel MD , Göksel Şener PhD , Mehmet Kızılay MD","doi":"10.1016/j.jvssci.2025.100405","DOIUrl":"10.1016/j.jvssci.2025.100405","url":null,"abstract":"<div><h3>Objective</h3><div>Oxidative stress and inflammation are widely recognized as central mechanisms in the pathogenesis of abdominal aortic aneurysm. This study sought to examine the potential protective properties of montelukast in a rat model of aortic aneurysm.</div></div><div><h3>Methods</h3><div>Male Sprague-Dawley rats were randomly allocated into three experimental groups. Abdominal aortic aneurysm was induced using the calcium chloride (CaCl<sub>2</sub>) model, in which gauze soaked in 0.5 M CaCl<sub>2</sub> was placed directly onto the adventitial surface of the infrarenal abdominal aorta for 15 minutes. After induction, the treatment group received daily intraperitoneal injections of montelukast (10 mg/kg) for 4 consecutive weeks. At the study end point, animals were euthanized, and infrarenal aortic tissues were harvested for biochemical and histological evaluations. Measured parameters included matrix metalloproteinase (MMP)-2 and MMP-9 expression, myeloperoxidase (MPO) activity, and 8-hydroxy-2′-deoxyguanosine levels. Antioxidant capacity was assessed through superoxide dismutase (SOD) activity assays. Histopathological examinations were performed, and statistical analysis was conducted using GraphPad Prism v.5.</div></div><div><h3>Results</h3><div>Exposure to CaCl<sub>2</sub> triggered pronounced oxidative injury and inflammation, as evidenced by elevated 8-hydroxy-2′-deoxyguanosine levels, increased MPO activity, reduced SOD activity, and upregulated MMP-2 and MMP-9 expression. Montelukast administration markedly attenuated these changes, normalizing oxidative and inflammatory markers while improving histopathological architecture.</div></div><div><h3>Conclusions</h3><div>Montelukast effectively counteracted CaCl<sub>2</sub>-induced aortic damage. The protective effects of montelukast appear to be mediated through suppression of MMP activity, restoration of SOD levels, and reduction of MPO-driven oxidative injury. By mitigating both inflammatory and oxidative mechanisms, montelukast contributes to the preservation of aortic wall structure.</div></div><div><h3>Clinical Relevance</h3><div>Abdominal aortic aneurysm remains a major vascular disorder without an effective pharmacological therapy to slow its progression. In this experimental study, montelukast, a leukotriene receptor antagonist widely used in asthma, attenuated abdominal aortic aneurysm formation in rats and was associated with increased superoxide dismutase activity, reduced myeloperoxidase levels, and suppressed matrix metalloproteinase activation. These combined antioxidant, anti-inflammatory, and matrix-stabilizing effects preserved aortic wall integrity. Given montelukast's established safety and clinical availability, these findings support its potential for future clinical investigation as a pharmacological approach to limit aneurysm progression.</div></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"7 ","pages":"Article 100405"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927781","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}
Pub Date : 2026-01-01DOI: 10.1016/j.jvssci.2025.100398
Bowen Wang PhD
{"title":"Adipocyte renin-angiotensin system signaling in periaortic fat: Neutral findings with mechanistic implications","authors":"Bowen Wang PhD","doi":"10.1016/j.jvssci.2025.100398","DOIUrl":"10.1016/j.jvssci.2025.100398","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"7 ","pages":"Article 100398"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927782","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}
Pub Date : 2025-11-27DOI: 10.1016/j.jvssci.2025.100397
Yasir AlSiraj PhD , Kelly Putnam PhD , Seth I. Brunner BS , Victoria L. English PhD , Charles M. Ensor PhD , Lisa A. Cassis PhD
<div><h3>Objective</h3><div>Adipocytes express renin–angiotensin system (RAS) components, including angiotensinogen (<em>Agt</em>), the precursor to angiotensin II (AngII), and the angiotensin type 1a receptor (<em>AT1aR</em>). The RAS contributes to atherosclerosis, and AngII infusion causes abdominal aortic aneurysm (AAA) formation. We studied effects of adipocyte <em>Agt</em> or <em>AT1aR</em> deficiency on diet-induced atherosclerosis and AngII-induced AAAs in male low-density lipoprotein receptor (<em>Ldlr</em>)-deficient mice.</div></div><div><h3>Methods</h3><div>For atherosclerosis, adipocyte <em>Agt-</em> or <em>AT1aR</em>-deficient <em>Ldlr</em>-deficient mice and littermate controls were fed a Western diet for 3 months. For AAAs, adipocyte <em>Agt-</em> or <em>AT1aR</em>-deficient <em>Ldlr</em><sup><em>−/−</em></sup> mice and littermate controls were fed a Western diet and infused with AngII (1000 ng/kg/min) for 28 days. Atherosclerosis was quantified en face in the aortic arch by the percent of intimal surface area covered by an atherosclerotic lesion. Serum (cholesterol, triglyceride) and plasma renin activity were quantified at study end point. AAAs were quantified in vivo by ultrasound quantification of abdominal aortic lumen diameters in anesthetized mice or at study end point by quantifying maximal external abdominal aortic diameter and AAA incidence (percent). Systolic blood pressure was quantified in AngII-infused mice by tail cuff plethysmography. Adipocyte size was quantified in tissue sections of white adipose tissue. Male <em>Ldlr</em><sup><em>−/−</em></sup> mice were fed a standard diet or a Western diet (1 or 3 months) and <em>Agt</em> or <em>AT1aR</em> messenger RNA (mRNA) abundance quantified in periaortic fat (PAF) by reverse transcriptase polymerase chain reaction.</div></div><div><h3>Results</h3><div>There was no effect of adipocyte <em>Agt</em> deficiency on body weight, serum cholesterol concentrations, or atherosclerotic lesions of Western diet-fed <em>Ldlr</em><sup><em>−/−</em></sup> mice. Adipocyte <em>Agt</em> deficiency had no effect on body weight, serum cholesterol concentrations, abdominal aortic lumen diameter, AAA incidence, or atherosclerosis of AngII-infused <em>Ldlr</em><sup><em>−/−</em></sup> mice. There was no effect of adipocyte AT1aR deficiency on body weight, serum cholesterol concentrations, or atherosclerotic lesions of Western diet-fed <em>Ldlr</em><sup><em>−/−</em></sup> mice. Control, but not adipocyte <em>AT1aR</em>-deficient mice lost weight during AngII infusion. The size of adipocytes in white adipose tissue was increased in adipocyte <em>AT1aR</em>-deficient mice with no significant influences on abdominal aortic lumen diameter, AAA incidence, or atherosclerosis of AngII-infused mice. In mice fed a Western diet for 1 or 3 months, <em>Agt</em> mRNA abundance in abdominal PAF increased over time in both diet groups, with modest diet-induced decreases in thoracic PAF <em>Agt</em> mRNA abunda
{"title":"Role of adipocyte angiotensinogen or angiotensin type 1a receptors in the development of diet-induced atherosclerosis or angiotensin II-induced abdominal aortic aneurysms","authors":"Yasir AlSiraj PhD , Kelly Putnam PhD , Seth I. Brunner BS , Victoria L. English PhD , Charles M. Ensor PhD , Lisa A. Cassis PhD","doi":"10.1016/j.jvssci.2025.100397","DOIUrl":"10.1016/j.jvssci.2025.100397","url":null,"abstract":"<div><h3>Objective</h3><div>Adipocytes express renin–angiotensin system (RAS) components, including angiotensinogen (<em>Agt</em>), the precursor to angiotensin II (AngII), and the angiotensin type 1a receptor (<em>AT1aR</em>). The RAS contributes to atherosclerosis, and AngII infusion causes abdominal aortic aneurysm (AAA) formation. We studied effects of adipocyte <em>Agt</em> or <em>AT1aR</em> deficiency on diet-induced atherosclerosis and AngII-induced AAAs in male low-density lipoprotein receptor (<em>Ldlr</em>)-deficient mice.</div></div><div><h3>Methods</h3><div>For atherosclerosis, adipocyte <em>Agt-</em> or <em>AT1aR</em>-deficient <em>Ldlr</em>-deficient mice and littermate controls were fed a Western diet for 3 months. For AAAs, adipocyte <em>Agt-</em> or <em>AT1aR</em>-deficient <em>Ldlr</em><sup><em>−/−</em></sup> mice and littermate controls were fed a Western diet and infused with AngII (1000 ng/kg/min) for 28 days. Atherosclerosis was quantified en face in the aortic arch by the percent of intimal surface area covered by an atherosclerotic lesion. Serum (cholesterol, triglyceride) and plasma renin activity were quantified at study end point. AAAs were quantified in vivo by ultrasound quantification of abdominal aortic lumen diameters in anesthetized mice or at study end point by quantifying maximal external abdominal aortic diameter and AAA incidence (percent). Systolic blood pressure was quantified in AngII-infused mice by tail cuff plethysmography. Adipocyte size was quantified in tissue sections of white adipose tissue. Male <em>Ldlr</em><sup><em>−/−</em></sup> mice were fed a standard diet or a Western diet (1 or 3 months) and <em>Agt</em> or <em>AT1aR</em> messenger RNA (mRNA) abundance quantified in periaortic fat (PAF) by reverse transcriptase polymerase chain reaction.</div></div><div><h3>Results</h3><div>There was no effect of adipocyte <em>Agt</em> deficiency on body weight, serum cholesterol concentrations, or atherosclerotic lesions of Western diet-fed <em>Ldlr</em><sup><em>−/−</em></sup> mice. Adipocyte <em>Agt</em> deficiency had no effect on body weight, serum cholesterol concentrations, abdominal aortic lumen diameter, AAA incidence, or atherosclerosis of AngII-infused <em>Ldlr</em><sup><em>−/−</em></sup> mice. There was no effect of adipocyte AT1aR deficiency on body weight, serum cholesterol concentrations, or atherosclerotic lesions of Western diet-fed <em>Ldlr</em><sup><em>−/−</em></sup> mice. Control, but not adipocyte <em>AT1aR</em>-deficient mice lost weight during AngII infusion. The size of adipocytes in white adipose tissue was increased in adipocyte <em>AT1aR</em>-deficient mice with no significant influences on abdominal aortic lumen diameter, AAA incidence, or atherosclerosis of AngII-infused mice. In mice fed a Western diet for 1 or 3 months, <em>Agt</em> mRNA abundance in abdominal PAF increased over time in both diet groups, with modest diet-induced decreases in thoracic PAF <em>Agt</em> mRNA abunda","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"7 ","pages":"Article 100397"},"PeriodicalIF":2.0,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145841692","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}
Pub Date : 2025-11-25DOI: 10.1016/j.jvssci.2025.100396
Nithya Ramesh PhD , Edward Downey BS , Sudheer Kumar Kanumuri MD , Zhenguo Liu MD , Venkateswaran Subramanian PhD
Thoracic aortic aneurysm (TAA) development involves disruption of extracellular matrix structural proteins such as collagen and elastin. An increased level of Galectin-3 (Gal-3), a β-galactoside-binding lectin, was reported in ascending aortic aneurysmal patients. To examine the role of Gal-3 on TAA formation in mice, two models were used: administration of lysyl oxidase inhibitor, β-aminopropionitrile (BAPN 0.5%, 0.3%, and 0.1% wt/vol) to 3- to 4 -week-old male and female Gal-3 wild-type (WT) or deficient knockout (KO) mice for 4 weeks in drinking water; and 8- to 10-week-old Gal-3 WT or KO mice were infused with either saline or angiotensin II (AngII) via osmotic mini-pumps for 28 days. High or low doses of BAPN administration promoted TAA rupture-induced death equivalently in both WT and KO male (WT = 64%; KO = 73%) and female (WT = 41%; KO = 54%) mice compared with controls. Similarly, AngII infusion caused a significantly increased, but equivalent, dilation of thoracic aortas in both male and female Gal-3 and Gal-3 KO mice compared with controls. Histological analysis revealed increased elastin fragmentation and collagen accumulation in both BAPN- and AngII-infused male and female WT and KO mice compared with controls. These findings suggest that Gal-3 deficiency did not influence either BAPN- or AngII-induced TAA formation or rupture in mice.
{"title":"Galectin-3 is dispensable for thoracic aortic aneurysmal formation and rupture in mice","authors":"Nithya Ramesh PhD , Edward Downey BS , Sudheer Kumar Kanumuri MD , Zhenguo Liu MD , Venkateswaran Subramanian PhD","doi":"10.1016/j.jvssci.2025.100396","DOIUrl":"10.1016/j.jvssci.2025.100396","url":null,"abstract":"<div><div>Thoracic aortic aneurysm (TAA) development involves disruption of extracellular matrix structural proteins such as collagen and elastin. An increased level of Galectin-3 (Gal-3), a β-galactoside-binding lectin, was reported in ascending aortic aneurysmal patients. To examine the role of Gal-3 on TAA formation in mice, two models were used: administration of lysyl oxidase inhibitor, β-aminopropionitrile (BAPN 0.5%, 0.3%, and 0.1% wt/vol) to 3- to 4 -week-old male and female Gal-3 wild-type (WT) or deficient knockout (KO) mice for 4 weeks in drinking water; and 8- to 10-week-old Gal-3 WT or KO mice were infused with either saline or angiotensin II (AngII) via osmotic mini-pumps for 28 days. High or low doses of BAPN administration promoted TAA rupture-induced death equivalently in both WT and KO male (WT = 64%; KO = 73%) and female (WT = 41%; KO = 54%) mice compared with controls. Similarly, AngII infusion caused a significantly increased, but equivalent, dilation of thoracic aortas in both male and female Gal-3 and Gal-3 KO mice compared with controls. Histological analysis revealed increased elastin fragmentation and collagen accumulation in both BAPN- and AngII-infused male and female WT and KO mice compared with controls. These findings suggest that Gal-3 deficiency did not influence either BAPN- or AngII-induced TAA formation or rupture in mice.</div></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"7 ","pages":"Article 100396"},"PeriodicalIF":2.0,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765721","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}
Pub Date : 2025-01-01DOI: 10.1016/j.jvssci.2025.100291
Weichen Hong BS , Vijay Tewari BS , Huidan Yu PhD , Jun Chen PhD , Alan P. Sawchuk MD
Compliance mismatch between native arteries and prosthetic grafts contribute to complications such as neointimal hyperplasia and pseudoaneurysms, leading to reduced graft patency. Three-dimensional (3D) printing offers a promising solution by flexibly customizing mechanical properties using elastic polymers. This study investigates whether 3D-printed polymeric grafts can better replicate native arterial compliance compared with commercial prosthetic grafts. We conducted compliance tests on human aortoiliac arteries, polytetrafluoroethylene (PTFE) grafts, Dacron grafts, and 3D-printed arteries with BioMed Elastic Resin within a mock circulation loop. All samples shared controlled geometry and were tested under the same physiological flow conditions. Pressure waveforms and key hemodynamic parameters were recorded and analyzed. The 3D-printed graft demonstrated a compliance of 0.49 cm3/mmHg, more closely matching the human artery than PTFE (0.38 cm3/mmHg) and Dacron (0.45 cm3/mmHg). Its mean arterial pressure (82 ± 0.6 mmHg) and peak pressure (40 ± 0.7 mmHg) in the flow loop also aligned more closely with the native artery compared with conventional grafts. Standard prosthetic graft materials have remained relatively static, whereas there has been immense advancement in new polymer technology. These polymers can match the compliance of native vessels, theoretically reducing complications associated with traditional grafts, and future work should investigate their biocompatibility, durability, and clinical feasibility.
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Treatment with an inhibitor of glucose use via glucose transporters (GLUT) has been shown to attenuate experimental abdominal aortic aneurysm (AAA) development in mice. Vascular smooth muscle cell (VSMC) signaling seems to be essential for angiotensin II (Ang II)-induced AAA in mice. Accordingly, we have tested a hypothesis that VSMC silencing of the major GLUT, GLUT1, prevents AAA development and rupture in mice treated with Ang II plus β-aminopropionitrile. A mouse model of inducible VSMC GLUT1 deletion was created and aortic GLUT1 silencing was confirmed. Without Ang II plus β-aminopropionitrile treatment, no difference was observed regarding the external aortic diameter (control 1.06 ± 0.18 mm vs deletion 0.97 ± 0.26 mm) or systolic blood pressure (control 102 ± 9 mm Hg vs deletion 107 ± 11 mm Hg) between control or GLUT1-silenced mice. With treatment, control mice as well as VSMC GLUT1-silenced mice equally developed AAA (control 2.37 ± 0.75 mm vs deletion 2.41 ± 0.93 mm), whereas a tendency toward lower blood pressure was observed in GLUT1 silenced mice (control 150 ± 9 mm Hg vs deletion 135 ± 22 mm Hg). No significant difference was observed regarding the rate of rupture-dependent mortality. We concluded that VSMC GLUT1 is dispensable for AAA development induced by Ang II in mice.
研究表明，使用葡萄糖转运体（GLUT）葡萄糖利用抑制剂可减轻小鼠实验性腹主动脉瘤（AAA）的发生。血管平滑肌细胞（VSMC）信号传导似乎对血管紧张素 II（Ang II）诱导的小鼠 AAA 至关重要。因此，我们测试了一个假设，即血管平滑肌细胞（VSMC）沉默主要的 GLUT（GLUT1）可防止血管紧张素 II 加 β-氨基丙腈治疗小鼠 AAA 的发生和破裂。建立了诱导性血管内皮细胞 GLUT1 缺失的小鼠模型，并证实了主动脉 GLUT1 沉默。在未接受 Ang II 和 β-氨基丙腈治疗的情况下，对照组和 GLUT1 沉默小鼠的主动脉外径（对照组为 1.06 ± 0.18 mm，缺失组为 0.97 ± 0.26 mm）或收缩压（对照组为 102 ± 9 mm Hg，缺失组为 107 ± 11 mm Hg）均无差异。经过治疗后，对照组小鼠和 VSMC GLUT1 沉默小鼠同样发展为 AAA（对照组 2.37 ± 0.75 mm vs 基因缺失组 2.41 ± 0.93 mm），而 GLUT1 沉默小鼠的血压趋于降低（对照组 150 ± 9 mm Hg vs 基因缺失组 135 ± 22 mm Hg）。在破裂依赖性死亡率方面没有观察到明显差异。我们的结论是，血管内皮细胞 GLUT1 对于 Ang II 诱导的小鼠 AAA 的发展是不可或缺的。
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