{"title":"Neointimal Smooth Muscle Cells in Mouse Vein Grafts Are Not Recruited from the Adjacent Artery.","authors":"Klas Österberg, Joakim Håkansson, Erney Mattsson","doi":"10.1159/000546237","DOIUrl":"10.1159/000546237","url":null,"abstract":"<p><strong>Introduction: </strong>Smooth muscle cells (SMCs) with an origin separate from the local vein wall contribute to formation of intimal hyperplasia (IH) in mouse vein grafts. The recruitment pathway of these cells has not been defined, but circulating progenitor cells and cells from the surrounding tissue or adjacent artery to which the vein graft is anastomosed are potential sources. The aim of this study was to clarify if cells from the adjacent artery contribute to neointimal formation in vein grafts.</p><p><strong>Methods: </strong>Aortic segments from donor SM22α-LacZ mice were anastomosed to vein segments from wild-type (WT) C57BL/6 mice ex vivo followed by implantation of the composite grafts to the right common carotid arteries of WT recipient mice. Six weeks after surgery, the composite grafts were harvested, and histology was analyzed in longitudinal sections. SMCs with origin in the SM22α-LacZ arterial segments were identified with X-gal staining.</p><p><strong>Results: </strong>LacZ-positive cells were found in the medial layer of the SM22α-LacZ arterial segments but were not found in the IH in the vein graft segment.</p><p><strong>Conclusion: </strong>SMCs in vein grafts are not recruited from the adjacent artery through migration across the anastomosis.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"1-8"},"PeriodicalIF":1.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Min-Hyeok Jang, Song-Young Park, Sun Dong Kim, Sang Ho Lee
{"title":"Heat Therapy as a Viable Treatment for Peripheral Artery Disease-A Mini Review.","authors":"Min-Hyeok Jang, Song-Young Park, Sun Dong Kim, Sang Ho Lee","doi":"10.1159/000546163","DOIUrl":"https://doi.org/10.1159/000546163","url":null,"abstract":"<p><p>Peripheral artery disease (PAD) is a prevalent and debilitating condition characterized by reduced blood flow to the lower limb extremities due to arterial plaque buildup. Traditional exercise/walking therapies have been used to improve vascular function and walking performance but suffer from low adherence rates due to pain and discomfort. Heat therapy has emerged as a promising alternative, showing similar improvements in vascular and cardiovascular function, often with higher adherence rates. This review explores various forms of heat therapy, including passive and active modalities, and compares them with traditional exercise/walking therapies. Despite promising results, further research is needed to standardize heat therapy protocol and understand the underlying mechanisms. Optimizing heat therapy could offer a viable, patient-friendly alternative to improve vascular function, reduce pain, and enhance quality of life in patients with PAD.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"1-21"},"PeriodicalIF":1.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Functional Unit of the Lymphatic System: Towards Understanding the Importance of a Well-Rehearsed Interaction of Lymphatic Capillaries, Collecting Vessels, and Lymph Nodes.","authors":"Katrin Sabine Roth, Reinhard Pabst","doi":"10.1159/000545084","DOIUrl":"10.1159/000545084","url":null,"abstract":"<p><strong>Introduction: </strong>Lymphatic vessels and lymph nodes (LNs) are part of the lymphatic system taking care of interstitial tissue homoeostasis, lipid transport, and immune response. The interposition of LNs in between the lymphatic vasculature allows the filtration of lymph fluid, cell-cell interactions, and also the transfer of lymph fluid into the venous system. An important role of lymphatic flow, which is often underestimated, is the active involvement of lymph flow and the lymphatic vasculature in immunologic function.</p><p><strong>Summary: </strong>The present review summarizes the current knowledge of the different functional units of the lymphatic transport system trying to create a model of their interplay and options to react to inflammatory conditions. Remodelling of the lymphatic system during inflammation includes lymphangiogenesis, changed fluid transport rates, and modification of LN morphology. Alterations of these processes can aggravate inflammatory processes, leading to an incomplete resolution of the inflammation and often ending in chronic inflammatory condition. Despite the development of histological markers to visualize lymphatic vessels, new imaging methods and increased knowledge about the different parts of the lymphatic system the general overview about the interplay of the different components is missing.</p><p><strong>Key messages: </strong>We show the importance of lymphatic flow in the initiation of the immune response and the solution of an inflammation. We speculate that the increase in density and vessel diameter of lymph vessels is necessary to increase the fluid influx, efflux and the migration of cells into the LN. A failure of antigen-tissue clearance leads to chronic inflammation. Remodelling of LN morphology and vasculature is also necessary in this reaction. An overrun of the defending capacity of the LN is prevented by the immune system via control of the lymph vessel transport capacity and LN remodelling.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"1-10"},"PeriodicalIF":1.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Micah Hunter-Chang, Christine L Flora, Hema Kothari, Chantel C McSkimming, Sydney D Blimbaum, Corey M Williams, Angela M Taylor, Stefan Bekiranov, Coleen A McNamara
{"title":"Unstable Coronary Artery Plaque Features in Humans Are Associated with Higher Frequency of Circulating CD56bright Natural Killer Cells.","authors":"Micah Hunter-Chang, Christine L Flora, Hema Kothari, Chantel C McSkimming, Sydney D Blimbaum, Corey M Williams, Angela M Taylor, Stefan Bekiranov, Coleen A McNamara","doi":"10.1159/000544884","DOIUrl":"10.1159/000544884","url":null,"abstract":"<p><strong>Introduction: </strong>Unstable human artery plaques can suddenly rupture, leading to MI or stroke. Identification of blood markers associated with unstable plaque features is clearly needed. Humans with symptomatic carotid atherosclerotic plaques have increased infiltration of CD56bright natural killer (NK) cells into the plaque, yet whether subjects with unstable coronary artery plaque features have increased frequencies of circulating CD56bright NK cells is unknown.</p><p><strong>Methods: </strong>Coronary artery intravascular ultrasound (IVUS) was performed on subjects presenting for medically indicated coronary angiography. Eighteen subjects stratified into high and low percent (%) necrotic core and matched for age, body mass index (BMI), and lipids underwent mass cytometry by time-of-flight analysis on their peripheral blood mononuclear cells collected prior to imaging. Clustering of major immune cell populations was performed on live singlets and CD56 bright and dim NK subsets were quantitated.</p><p><strong>Results: </strong>Subjects with high necrotic core had a significantly greater frequency of circulating CD56bright NK cells compared to subjects with low necrotic core (p = 0.02). Additionally, the frequency of circulating CD56bright NK cells positively associated with IVUS-VH metrics of total atheroma volume (p = 0.0013), percent (%) atheroma burden (p = 0.0048), % maximum stenosis (p = 0.0021), % necrotic (p = 0.0013), % calcium (p = 0.0016), % fatty (p = 0.0097) and negatively associated with % fibrous (p < 0.0001), an IVUS-VH metric of plaque stability.</p><p><strong>Conclusion: </strong>These findings suggest that the frequency of CD56bright NK cells may be a safe, noninvasive marker of plaque volume and instability.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"1-7"},"PeriodicalIF":1.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Felipe T de Freitas Barão, Gina C Rocha Silvestre, Alexandre Queiroz Silva, Erasmo Simão da Silva
{"title":"Study of the Biomechanical and Histological Properties of the Thoracic Aorta of Diabetic Rats and Exposed to Cigarette Smoke.","authors":"Felipe T de Freitas Barão, Gina C Rocha Silvestre, Alexandre Queiroz Silva, Erasmo Simão da Silva","doi":"10.1159/000543322","DOIUrl":"10.1159/000543322","url":null,"abstract":"<p><strong>Introduction: </strong>Aortic aneurysm (AA) carries significant clinical implications due to its prevalence and potential complications. However, its etiopathogenesis remains poorly understood. The association between smoking and AA development has been consistently confirmed. Although AA was initially attributed to atherosclerosis, a negative association between diabetes (a major risk factor for atherosclerosis) and vascular aneurysmal disease has been observed. Investigating the biomechanical and histological properties of the aortic wall may shed light on the etiopathogenesis of aneurysms.</p><p><strong>Methods: </strong>This study involved 75 Wistar rats, divided into four groups: control (CG), smoker (SG), diabetic (DG), and diabetic plus smoker (DSG). Rats in the SG and DSG groups were exposed to cigarette smoke for 30 min daily, 5 days a week. Diabetes was induced by intravenous injection of streptozotocin. After 16 weeks, the animals were sacrificed to collect the thoracic aorta. Destructive uniaxial tensile tests were performed to obtain the following biomechanical failure properties: force, tension, stress, strain, and strain energy. Histological analysis of these fragments consisted of the percentage evaluation of collagen and elastic fibers and verification of the magnitude of the inflammatory process in the arterial wall. Metalloproteinase-9 activity in the aortic specimens was quantified through zymography.</p><p><strong>Results: </strong>Valid biomechanical tests of 36 specimens were analyzed, with 8 belonging to CG, 9 to DG, 11 to SG, and 8 to DSG. Biomechanical analysis of the fragments revealed that the maximum force and stress until rupture were lower in the DSG than in the SG with statistical significance. Evaluations of the percentage of collagen and elastic fibers as well as the inflammatory process showed no statistically significant difference among the groups studied. MMP-9 activity did not present a statistically significant difference among the different groups.</p><p><strong>Conclusions: </strong>The biomechanical properties related to resistance are lower in DSG than in SG while elasticity, histological changes related to collagen fiber, elastic fiber, and inflammatory process, and MMP-9 activity of the aortic wall of rats do not show differences between CG and DG, SG, and DSG. Based on the methodology employed in this study, it appears that the thoracic aorta is resilient against aneurysm development.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"1-12"},"PeriodicalIF":1.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amanda Balboa Ramilo, Nikiforos Chandrinos, Elefantia Tsichlia, Josefin Jönsson, Kevin Mani, Anders Wanhainen, Dick Wågsäter
{"title":"Evaluation of Metabolism-Associated Proteins in Abdominal Aortic Aneurysm.","authors":"Amanda Balboa Ramilo, Nikiforos Chandrinos, Elefantia Tsichlia, Josefin Jönsson, Kevin Mani, Anders Wanhainen, Dick Wågsäter","doi":"10.1159/000543768","DOIUrl":"10.1159/000543768","url":null,"abstract":"<p><strong>Introduction: </strong>Abdominal aortic aneurysm (AAA) development is inversely associated with diabetes mellitus. Targeting glucose metabolism seems to be a beneficial strategy for preventing AAA growth. Several metabolism-related factors are associated with AAA development. This study aimed to analyse the expression of the so far unstudied proteins irisin, follistatin, activin A, and ghrelin (ligand and receptor) in human and murine aneurysmal tissue, to assess the involvement of these pathways in AAA.</p><p><strong>Methods: </strong>Gene and protein expression was evaluated in aneurysmal and control tissue samples, by qPCR and immunohistochemistry. Vascular smooth muscle cells (VSMCs) were studied in vitro for expression. Circulating levels of the proteins of interest in human plasma samples were evaluated by ELISA.</p><p><strong>Results: </strong>In human aneurysmal tissue, the proteins of interest were predominantly expressed by VSMCs in neovessels. Expression by human VSMCs was confirmed in vitro. In human plasma, the concentration of irisin was higher in AAA (+/- diabetes) compared to controls. Patients with AAA and type 2 diabetes treated with metformin had lower levels of follistatin and ghrelin.</p><p><strong>Conclusion: </strong>This study demonstrates irisin, follistatin, and ghrelin as interesting proteins to be studied in the context of the observed negative association between AAA development and type 2 diabetes.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"1-12"},"PeriodicalIF":1.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Priyanka Böttger, Tilo Grosser, Waltraut Ibe, Jean-Paul Boissel, Stephan Lindemann, Karl Werdan, HansJörg Schwertz, Harald Darius, Michael Buerke
{"title":"Single Intraluminal Delivery of a Nitric Oxide-Donor Results in Inhibition of Intimal Thickening in the Rabbit Femoral Artery.","authors":"Priyanka Böttger, Tilo Grosser, Waltraut Ibe, Jean-Paul Boissel, Stephan Lindemann, Karl Werdan, HansJörg Schwertz, Harald Darius, Michael Buerke","doi":"10.1159/000544029","DOIUrl":"10.1159/000544029","url":null,"abstract":"<p><strong>Introduction: </strong>Vascular smooth muscle cell (SMC) proliferation and vascular homeostasis are thought to be regulated by nitric oxide and prostaglandins. The loss of these endogenous mediators seems to play an important role for the development of restenosis following balloon angioplasty.</p><p><strong>Methods: </strong>We examined the effect of exogenous linsidomine, a nitric oxide (NO) releasing compound, in a model of balloon injury iliac arteries of rabbits. On the cellular levels, NO can exert effects like cell survival, growth, and proliferation inhibition, has effects on transcription and proteasome effects and mitochondria-related effects in SMCs. SMC proliferation was quantified as a change of intima-media ratio. Linsidomine injection or its vehicle was performed with an infusion-balloon catheter directly into the dilated vessel wall.</p><p><strong>Results: </strong>Balloon angioplasty resulted in a significant increase of intima-media ratio during the first 3 weeks. Linsidomine treatment decreased the intima-media ratio significantly compared to vehicle treated animals 3 weeks after balloon angioplasty (0.65 ± 0.05 vs 1.2 ± 0.2 intima-media ratio, p < 0.05). However, control vessels had an intima-media ratio of 0.15 ± 0.02. This effect was similar to NOS-2 transfected vessels following angioplasty. Immunohistochemical analysis demonstrated the expression of the proliferating cellular nuclear antigen in dilated vessel of vehicle treated animals, which was reduced in linsidomine-treated rabbits. In in vitro experiments, linsidomine inhibited significantly and dose-dependently rabbit SMC proliferation measured by BrdU incorporation. Further linsidomine increased rate of apoptotic SMCs, however, this effect was p53 independent.</p><p><strong>Conclusion: </strong>Simultaneous angioplasty of the rabbit iliac artery and direct injection of linsidomine into the vessel wall seem to be an effective strategy to reduce neointima formation. Similar, local application of liposome encapsulation of human nitric oxide synthase-2 transfection resulted in potent inhibition of intima proliferation and SMC proliferation due to local restoration NO within the injured vasculature.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"1-11"},"PeriodicalIF":1.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dissecting Tunica Responsibility in Arterial Stress Relaxation: Smooth Muscle Need Not Apply.","authors":"Janice M Thompson, Stephanie W Watts","doi":"10.1159/000543871","DOIUrl":"10.1159/000543871","url":null,"abstract":"<p><strong>Introduction: </strong>Stress relaxation is considered a property of smooth muscle. Rings of thoracic aorta with/without perivascular adipose tissue (PVAT) stress relax. However, rings of isolated PVAT, containing no organized smooth muscle, also stress relax. We hypothesize that smooth muscle is not necessary in the individual tunicas of the aorta for stress relaxation to occur.</p><p><strong>Methods: </strong>Histochemical staining and isometric contractility were performed on whole or tunicas of the thoracic aorta from the male and female Dahl salt-sensitive rats on normal diet. Masson trichrome and Verhoeff Van Gieson staining validated the isolation of the different tunicas. Stress relaxation was measured after cumulative amounts of passive tension were applied in the presence or absence of extracellular Ca2+, followed by challenge with the a1 adrenergic agonist phenylephrine (PE, 10-5 M).</p><p><strong>Results: </strong>Stress relaxation occurred in all tunicas at each passive tension regardless of Ca2+. PE-induced contraction was observed in tissues containing smooth muscle (media, whole vessel) but not in the adventitia and aPVAT with Ca2+. No contraction was observed with no Ca2+.</p><p><strong>Conclusions: </strong>All tunicas of the rat thoracic aorta stress relax, doing so without dependence on smooth muscle or Ca2+. PVAT demonstrated the greatest ability to stress relax.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"1-13"},"PeriodicalIF":1.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inactivation of Notch1-TGF-β-Smads Signaling Pathway by Atorvastatin Improves Cardiac Function and Hemodynamic Performance in Acute Myocardial Infarction Rats.","authors":"Qi Kang, Mei Kang, Mengyun Yang, Taniya Fernando","doi":"10.1159/000542728","DOIUrl":"10.1159/000542728","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of this study was to determine the effects of atorvastatin on cardiac function and hemodynamics and to investigate its functional mechanism on cardiac fibrosis in acute myocardial infarction (AMI) rats.</p><p><strong>Methods: </strong>Cardiac functions and hemodynamic changes were evaluated in each group on day 28. Quantitative reverse transcription-polymerase chain reaction, Western blot, and immunohistochemistry were performed to detect the expression of notch1, transforming growth factor-β (TGF-β), Smad2, Smad7, as well as myocardial fibrosis factors (i.e., collagen I, collagen III, and galectin-3) in the myocardial tissues of AMI rats. The changes of myocardial cell structure and myocardial collagen fibers of AMI rats were observed with hematoxylin and eosin staining and Masson staining.</p><p><strong>Results: </strong>Atorvastatin improved the cardiac function and hemodynamic performance. Atorvastatin downregulated the expression of notch1, smad2, collagen I, and collagen III in AMI rats. Atorvastatin treatment decreased the transcription of notch1, TGF-β, and smad2, while it increased smad7 in AMI rats. Atorvastatin induced the downregulation of collagen I, collagen III, and galectin-3. Myocardial immunohistochemical analysis showed atorvastatin inhibited the expression of notch1, TGF-β, and smad2 in myocardial tissues.</p><p><strong>Conclusion: </strong>Atorvastatin inhibited myocardial fibrosis by interfering with notch1-TGF-β-smads signal pathways. In addition, it could mitigate myocardial remodeling and improve cardiac functions and hemodynamics.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"1-12"},"PeriodicalIF":1.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}