JVS-vascular science最新文献

{"title":"Mechanisms and efficacy of metformin-mediated suppression of established experimental abdominal aortic aneurysms","authors":"Baohui Xu MD, PhD ,&nbsp;Gang Li MD, PhD ,&nbsp;Yankui Li MD, PhD ,&nbsp;Hongping Deng MD, PhD ,&nbsp;Anna Cabot BS ,&nbsp;Jia Guo MD, PhD ,&nbsp;Makoto Samura MD, PhD ,&nbsp;Xiaoya Zheng MD, PhD ,&nbsp;Tiffany Chen BS ,&nbsp;Sihai Zhao MD, PhD ,&nbsp;Naoki Fujimura MD, PhD ,&nbsp;Ronald L. Dalman MD","doi":"10.1016/j.jvssci.2023.100102","DOIUrl":"10.1016/j.jvssci.2023.100102","url":null,"abstract":"<div><h3>Objective</h3><p>Metformin treatment attenuates experimental abdominal aortic aneurysm (AAA) formation, as well as reduces clinical AAA diameter enlargement in patients with diabetes. The mechanisms of metformin-mediated aneurysm suppression, and its efficacy in suppressing established experimental aneurysms, remain uncertain.</p></div><div><h3>Methods</h3><p>Experimental AAAs were created in male C57BL/6J mice via intra-aortic infusion of porcine pancreatic elastase. Metformin alone (250 mg/kg), or metformin combined with the 5′ AMP-activated protein kinase (AMPK) antagonist Compound C (10 mg/kg), were administered to respective mouse cohorts daily beginning 4 days following AAA induction. Further AAA cohorts received either the AMPK agonist AICA riboside (500 mg/kg) as positive, or vehicle (saline) as negative, controls. AAA progression in all groups was assessed via serial in vivo ultrasonography and histopathology at sacrifice. Cytokine-producing T cells and myeloid cellularity were determined by flow cytometric analyses.</p></div><div><h3>Results</h3><p>Metformin limited established experimental AAA progression at 3 (−85%) and 10 (−68%) days following treatment initiation compared with saline control. Concurrent Compound C treatment reduced this effect by approximately 50%. In metformin-treated mice, reduced AAA progression was associated with relative elastin preservation, smooth muscle cell preservation, and reduced mural leukocyte infiltration and neoangiogenesis compared with vehicle control group. Metformin also resulted in reduced interferon-γ-, but not interleukin-10 or -17, producing splenic T cells in aneurysmal mice. Additionally, metformin therapy increased circulating and splenic inflammatory monocytes (CD11b⁺Ly-6C^high), but not neutrophils (CD11b⁺Ly-6G⁺), with no effect on respective bone marrow cell populations.</p></div><div><h3>Conclusions</h3><p>Metformin treatment suppresses existing experimental AAA progression in part via AMPK agonist activity, limiting interferon-γ-producing T cell differentiation while enhancing circulating and splenic inflammatory monocyte retention.</p></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"4 ","pages":"Article 100102"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/18/c2/main.PMC10165270.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9458182","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":"Abdominal aortic aneurysms: insights into mechanical and extracellular matrix effects from mouse models","authors":"Hong S. Lu MD, PhD,&nbsp;Hisashi Sawada MD, PhD,&nbsp;Alan Daugherty PhD, DSc","doi":"10.1016/j.jvssci.2023.100099","DOIUrl":"10.1016/j.jvssci.2023.100099","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"4 ","pages":"Article 100099"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/73/60/main.PMC10172769.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9522678","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":"Rupture risk parameters upon biomechanical analysis independently change from vessel geometry during abdominal aortic aneurysm growth","authors":"David Zschäpitz MD ,&nbsp;Bianca Bohmann MSc ,&nbsp;Brigitta Lutz MD ,&nbsp;Hans-Henning Eckstein MD ,&nbsp;Christian Reeps MD ,&nbsp;Lars Maegdefessel MD, PhD ,&nbsp;Christian T. Gasser PhD ,&nbsp;Albert Busch MD, PhD","doi":"10.1016/j.jvssci.2022.10.004","DOIUrl":"10.1016/j.jvssci.2022.10.004","url":null,"abstract":"<div><h3>Objective</h3><p>The indication for abdominal aortic aneurysm (AAA) repair is based on a diameter threshold. However, mechanical properties, such as peak wall stress (PWS) and peak wall rupture index (PWRI), influence the individual rupture risk. This study aims to correlate biomechanical and geometrical AAA characteristics during aneurysm growth applying a new linear transformation-based comparison of sequential imaging.</p></div><div><h3>Methods</h3><p>Patients with AAA with two sequential computed tomography angiographies (CTA) were identified from a single-center aortic database. Patient characteristics included age, gender, and comorbidities. Semiautomated segmentation of CTAs was performed using Endosize (Therenva) for geometric variables (diameter, neck configuration, α/β angle, and vessel tortuosity) and for finite element method A4 Clinics Research Edition (Vascops) for additional variables (intraluminal thrombus [ILT]), vessel volume, PWS, PWRI). Maximum point coordinates from at least one CTA 6 to 24 months before their final were predicted for the final preoperative CTA using linear transformation along fix and validation points to estimate spatial motion. Pearson’s correlation and the <em>t</em> test were used for comparison.</p></div><div><h3>Results</h3><p>Thirty-two eligible patients (median age, 70 years) were included. The annual AAA growth rate was 3.7 mm (interquartile range [IQR], 2.25-5.44; <em>P</em> &lt; .001) between CTs. AAA (+17%; <em>P</em> &lt; .001) and ILT (+43%; <em>P</em> &lt; .001) volume, maximum ILT thickness (+35%; <em>P</em> &lt; .001), β angle (+1.96°; <em>P</em> = .017) and iliac tortuosity (+0.009; <em>P</em> = .012) increased significantly. PWS (+12%; <em>P</em> = .0029) and PWRI (+16%; <em>P</em> &lt; .001) differed significantly between both CTAs. Both mechanical parameters correlated most significantly with the AAA volume increase (r = 0.68 [<em>P</em> &lt; .001] and r = 0.6 [<em>P</em> &lt; .001]). Changes in PWS correlated best with the aneurysm neck configuration. The spatial motion of maximum ILT thickness was 14.4 mm (IQR, 7.3-37.2), for PWS 8.4 mm (IQR, 3.8-17.3), and 11.5 mm (IQR, 5.9-31.9) for PWRI. Here, no significant correlation with any of the aforementioned parameters, patient age, or time interval between CTs were observed.</p></div><div><h3>Conclusions</h3><p>PWS correlates highly significant with vessel volume and aneurysm neck configuration. Spatial motion of maximum ILT thickness, PWS, and PWRI is detectable and predictable and might expose different aneurysm wall segments to maximum stress throughout aneurysm growth. Linear transformation could thus add to patient-specific rupture risk analysis.</p></div><div><h3>Clinical Relevance</h3><p>Abdominal aortic aneurysm rupture risk assessment is a key feature in future individualized therapy approaches for patients, since more and more data are obtained concluding a heterogeneous disease entity that might not be addressed ideally","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"4 ","pages":"Article 100093"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9900617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10690201","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":"Aortic dissection detection and thrombus structure quantification using volumetric ultrasound, histology, and scanning electron microscopy","authors":"Luke E. Schepers BE ,&nbsp;Irina N. Chernysh BS, PhD ,&nbsp;Claudia K. Albrecht ,&nbsp;Luke C. Browning ,&nbsp;McKenna L. Hillsdon-Smith ,&nbsp;Abigail D. Cox BS, DVM, PhD ,&nbsp;John W. Weisel BS, PhD ,&nbsp;Craig J. Goergen BS, PhD","doi":"10.1016/j.jvssci.2023.100105","DOIUrl":"10.1016/j.jvssci.2023.100105","url":null,"abstract":"<div><p>Aortic dissection occurs when a weakened portion of the intima tears, and a separation of layers propagates along the aortic wall to form a false lumen filled with active blood flow or intramural thrombus. The unpredictable nature of aortic dissection formation and need for immediate intervention leaves limited serial human image data to study the formation and morphological changes that follow dissection. We used volumetric ultrasound examination, histology, and scanning electron microscopy (SEM) to examine intramural thrombi at well-defined timepoints after dissection occurs in apolipoprotein E-deficient mice infused with angiotensin II (n = 71). Stratification of red blood cell (RBC) morphologies (biconcave, intermediate biconcave, intermediate polyhedrocyte, and polyhedrocyte) in the thrombi with scanning electron microscopy (n = 5) was used to determine degree of thrombus deposition/contraction. Very few biconcave RBCs (1.2 ± 0.6%) were in the thrombi, and greater amounts of intermediate biconcave RBCs (25.8 ± 6.7%) were located in the descending thoracic portion of the dissection while more polyhedrocytes (14.6 ± 5.1%) and fibrin (42.3 ± 4.5%; <em>P &lt;</em> .05) were found in the distal suprarenal aorta. Thrombus deposition likely plays some role in patient outcomes, and this multimodality technique can help investigate thrombus deposition and characteristics in experimental animal models and human tissue samples.</p></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"4 ","pages":"Article 100105"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350323000093/pdfft?md5=4779124c86788fb539954c1afbe46159&pid=1-s2.0-S2666350323000093-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80065020","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":"Blockade of IL-6 Signaling Alleviates Atherosclerosis in Tet2 Deficient Clonal Hematopoiesis","authors":"Wenli Liu,&nbsp;Nan Wang,&nbsp;Alan Tall","doi":"10.1016/j.jvssci.2023.100175","DOIUrl":"https://doi.org/10.1016/j.jvssci.2023.100175","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"4 ","pages":"Article 100175"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350323000792/pdfft?md5=fcd7b6cda0b39a121c08f35665b5f0c2&pid=1-s2.0-S2666350323000792-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139107308","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":"Fatty Acid Synthase Targeting Reduces Aortic Atherosclerosis and Inflammation","authors":"Rodrigo Meade,&nbsp;Connor Engel,&nbsp;Larisa Belaygorod,&nbsp;Batool Arif,&nbsp;Wahid Abu-Amer,&nbsp;Clay F. Semenkovich,&nbsp;Mohamed A. Zayed","doi":"10.1016/j.jvssci.2023.100138","DOIUrl":"https://doi.org/10.1016/j.jvssci.2023.100138","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"4 ","pages":"Article 100138"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350323000421/pdfft?md5=ba5487b16222addf6897bd4759315d67&pid=1-s2.0-S2666350323000421-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139107353","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":"Physiologic Oxygen Conditions Preserve Induced Pluripotent Stem Cell-derived Endothelial Cell Progenitor Identity","authors":"Katherine Hekman ,&nbsp;Ottis Scrivner ,&nbsp;Dylan McLaughlin","doi":"10.1016/j.jvssci.2023.100177","DOIUrl":"https://doi.org/10.1016/j.jvssci.2023.100177","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"4 ","pages":"Article 100177"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350323000810/pdfft?md5=4a4468a7cd0aee9cba4bd8088e2ab5ff&pid=1-s2.0-S2666350323000810-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139108796","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":"Sex differences in specialized pro-resolving lipid mediators and their receptors in abdominal aortic aneurysms","authors":"Amanda C. Filiberto MD ,&nbsp;Victoria Leroy BS ,&nbsp;Zachary Ladd BS ,&nbsp;Gang Su MD ,&nbsp;Craig T. Elder MD ,&nbsp;Eric Y. Pruitt MD ,&nbsp;Guanyi Lu MD ,&nbsp;Joseph Hartman BS ,&nbsp;Ali Zarrinpar MD, PhD ,&nbsp;Timothy J. Garrett PhD ,&nbsp;Ashish K. Sharma MBBS, PhD ,&nbsp;Gilbert R. Upchurch Jr. MD","doi":"10.1016/j.jvssci.2023.100107","DOIUrl":"10.1016/j.jvssci.2023.100107","url":null,"abstract":"<div><h3>Objective</h3><p>In this study, we tested the hypothesis that endogenous expression of specialized pro-resolving lipid mediators (SPMs) that facilitate the resolution of inflammation, specifically Resolvin D1and -D2, as well as Maresin1 (MaR1), can impact abdominal aortic aneurysm (AAA) formation and progression in a sex-specific manner.</p></div><div><h3>Methods</h3><p>SPM expression was quantified in aortic tissue from human AAA samples and from a murine in vivo AAA model via liquid chromatography-tandem mass spectrometry. mRNA expression for SPM receptors FPR2, LGR6, and GPR18 were quantified by real-time polymerase chain reaction. A Student <em>t</em> test with nonparametric Mann-Whitney or Wilcoxon test was used for pair-wise comparisons of groups. One-way analysis of variance after post hoc Tukey test was used to determine the differences among multiple comparative groups.</p></div><div><h3>Results</h3><p>Human aortic tissue analysis revealed a significant decrease in RvD1 levels in male AAAs compared with controls, whereas FPR2 and LGR6 receptor expressions were downregulated in male AAAs compared with male controls. In vivo studies of elastase-treated mice showed higher levels of RvD2 and MaR1 as well as the SPM precursors, omega-3 fatty acids DHA and EPA, in aortic tissue from males compared with females. FPR2 expression was increased in elastase-treated females compared with males.</p></div><div><h3>Conclusions</h3><p>Our findings demonstrate that specific differences in SPMs and their associated G-protein coupled receptors exist between sexes. These results indicate the relevance of SPM-mediated signaling pathways in sex differences impacting the pathogenesis of AAAs.</p></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"4 ","pages":"Article 100107"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3f/6a/main.PMC10245328.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9612484","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":"Introduction to the JVS-VS Special Issue, “Aneurysms”","authors":"David A. Vorp PhD","doi":"10.1016/j.jvssci.2023.100110","DOIUrl":"10.1016/j.jvssci.2023.100110","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"4 ","pages":"Article 100110"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d6/50/main.PMC10319305.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10161626","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":"Chronic nicotine impairs the angiogenic capacity of human induced pluripotent stem cell-derived endothelial cells in a murine model of peripheral arterial disease","authors":"Alex H.P. Chan PhD ,&nbsp;Caroline Hu BS ,&nbsp;Gladys C.F. Chiang BS ,&nbsp;Chisomaga Ekweume BS ,&nbsp;Ngan F. Huang PhD","doi":"10.1016/j.jvssci.2023.100115","DOIUrl":"10.1016/j.jvssci.2023.100115","url":null,"abstract":"<div><h3>Objective</h3><p>Lifestyle choices such as tobacco and e-cigarette use are a risk factor for peripheral arterial disease (PAD) and may influence therapeutic outcomes. The effect of chronic nicotine exposure on the angiogenic capacity of human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) was assessed in a murine model of PAD.</p></div><div><h3>Methods</h3><p>Mice were exposed to nicotine or phosphate-buffered saline (PBS) for 28 days, followed by induction of limb ischemia and iPSC-EC transplantation. Cells were injected into the ischemic limb immediately after induction of hindlimb ischemia and again 7 days later. Limb perfusion was assessed by laser Doppler spectroscopy, and transplant cell survival was monitored for 14 days afterward using bioluminescence imaging, followed by histological analysis of angiogenesis.</p></div><div><h3>Results</h3><p>Transplant cell retention progressively decreased over time after implantation based on bioluminescence imaging, and there were no significant differences in cell survival between mice with chronic exposure to nicotine or PBS. However, compared with mice without nicotine exposure, mice with prior nicotine exposure had had an impaired therapeutic response to iPSC-EC therapy based on decreased vascular perfusion recovery. Mice with nicotine exposure, followed by cell transplantation, had significantly lower mean perfusion ratio after 14 days (0.47 ± 0.07) compared with mice undergoing cell transplantation without prior nicotine exposure (0.79 ± 0.11). This finding was further supported by histological analysis of capillary density, in which animals with prior nicotine exposure had a lower capillary density (45.9 ± 4.7 per mm²) compared with mice without nicotine exposure (66.5 ± 8.1 per mm²). Importantly, the ischemic limbs mice exposed to nicotine without cell therapy also showed significant impairment in perfusion recovery after 14 days, compared with mice that received PBS + iPSC-EC treatment. This result suggested that mice without chronic nicotine exposure could respond to iPSC-EC implantation into the ischemic limb by inducing perfusion recovery, whereas mice with chronic nicotine exposure did not respond to iPSC-EC therapy.</p></div><div><h3>Conclusions</h3><p>Together, these findings show that chronic nicotine exposure adversely affects the ability of iPSC-EC therapy to promote vascular perfusion recovery and angiogenesis in a murine PAD model.</p></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"4 ","pages":"Article 100115"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3d/87/main.PMC10372313.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9899687","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}