Journal of Vascular Research最新文献

{"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":"https://doi.org/10.1159/000545084","url":null,"abstract":"<p><p>Lymphatic vessels and lymph nodes (LNs) are part of the lymphatic system taking care of interstitial tissue homeostasis, 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. Impairment of the lymphatic vasculature leads to interstitial fluid congestion leading to tissue oedema as seen in acute inflammation or trauma or i.e. in lymphedema of the skin as a chronic condition. 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. 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. In a last step open questions are gathered together and possible answers discussed.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"1-14"},"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}

{"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><p>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 plaque infiltration of CD56bright Natural Killer (NK) cells, yet whether subjects with unstable coronary artery plaque features have increased frequencies of circulating CD56bright NK cells is unknown. Coronary artery intravascular ultrasound (IVUS) was performed on subjects presenting for medically-indicated coronary angiography. 18 subjects stratified into high and low percent (%) necrotic core matched for age, BMI, and lipids underwent Mass Cytometry (CyTOF) analysis on their peripheral blood mononuclear cells (PBMCs). Clustering of major PBMC populations was performed on live singlets and CD56 bright and dim NK subsets were quantitated. Subjects with high necrotic core had significantly greater frequency of circulating CD56bright NK cells compared to subjects with low necrotic core (p=0.02). Additionally, frequency of CD56bright NK cells positively associated with IVUS-VH metrics of total atheroma volume (TAV) (p=0.0013), percent (%) atheroma burden (p=0.0048), % maximum stenosis (p=0.0021), % necrotic (p=0.0013), % calcium (p=0.0016)) and negatively associated with % fibrous (p<0.0001). These findings suggest that frequency of CD56bright NK cells may be a safe, non-invasive marker of plaque volume and instability.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"1-12"},"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}

{"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}

{"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}

{"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}

{"title":"Relationship between Oxidative Balance Score and All-Cause Mortality in Hypertension.","authors":"Tianyi Ma, Ling Wang, Xiaorong Yan","doi":"10.1159/000543471","DOIUrl":"10.1159/000543471","url":null,"abstract":"<p><strong>Introduction: </strong>Exploring the association between oxidative balance score (OBS) and all-cause mortality in hypertension (HTN).</p><p><strong>Methods: </strong>Data for HTN patients from 2007 to 2018 were extracted from the National Health and Nutrition Examination Survey (NHANES). OBS offers a thorough evaluation of an individual's redox status, with higher score indicates favorable oxidative homeostasis. All-cause mortality was obtained by linkage to National Death Index records through 31 December 2019. Weighted multivariable Cox regression models, Kaplan-Meier curves, receiver operator characteristic curve, and random survival forests (RSF) analysis were applied to examine the relationship between OBS and all-cause mortality in HTN.</p><p><strong>Results: </strong>The cohort included 13,130 participants, with 2,132 deaths. Higher OBS was associated with lower all-cause mortality risk (HR = 0.77, 95% CI: 0.65-0.91) in HTN. The relationship also existed in subgroups of male, having/have not chronic kidney disease, and having cardiovascular disease. Kaplan-Meier curves suggested that participants with higher OBS had superior survival rates compared to those with lower intake. The RSF showed a better survival predictive role for physical activity among the components of OBS.</p><p><strong>Conclusion: </strong>Higher OBS was related to lower odds of all-cause mortality in patients with HTN. Adopting a healthy lifestyle and consuming an antioxidant-rich diet may improve the prognosis of patients with HTN.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"1-12"},"PeriodicalIF":1.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007752","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":"A Novel in vivo Rat Mesentery Model for Studying Tumor Spheroid-Induced Microvascular Remodeling.","authors":"Arinola O Lampejo, Luciana Fonseca Perez, Miriam M Girgis, Blanka Sharma, Dietmar W Siemann, Walter L Murfee","doi":"10.1159/000543011","DOIUrl":"10.1159/000543011","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The tumor microenvironment is comprised of neoplastic cells and a variety of host cell types. Investigation of cell dynamics within this environment has motivated in vitro and ex vivo biomimetic model development. Our laboratory recently introduced the tumor spheroid-rat mesentery culture model to investigate cancer-induced lymphatic/blood vessel remodeling. To validate the physiological relevance of this model, the objective of this study was to determine the effect of tumor spheroids on microvascular remodeling after transplantation onto rat mesenteric tissues in vivo.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Spheroids derived from H1299 lung cancer cells were seeded onto rat mesenteric tissues during a survival surgical procedure. Tissues were harvested 3-5 days post-seeding and stained with PECAM and LYVE-1 to identify blood and lymphatic vessels, respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;At all timepoints, cancer cells remained adhered to the tissue. Tissues seeded with tumor spheroids were shown to have increased vascular density, capillary sprouting, and tortuosity compared to sham tissues exposed to sterile saline only. Tumor spheroids also induced the formation of lymphatic/blood vessel connections and LYVE-1-negative protrusions emerging from lymphatic vessels.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Overall, this study underscores the use of in vivo modeling to aid in the discovery of novel vascular growth dynamics and offers new methodologies for studying tumor-induced remodeling.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The tumor microenvironment is comprised of neoplastic cells and a variety of host cell types. Investigation of cell dynamics within this environment has motivated in vitro and ex vivo biomimetic model development. Our laboratory recently introduced the tumor spheroid-rat mesentery culture model to investigate cancer-induced lymphatic/blood vessel remodeling. To validate the physiological relevance of this model, the objective of this study was to determine the effect of tumor spheroids on microvascular remodeling after transplantation onto rat mesenteric tissues in vivo.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Spheroids derived from H1299 lung cancer cells were seeded onto rat mesenteric tissues during a survival surgical procedure. Tissues were harvested 3-5 days post-seeding and stained with PECAM and LYVE-1 to identify blood and lymphatic vessels, respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;At all timepoints, cancer cells remained adhered to the tissue. Tissues seeded with tumor spheroids were shown to have increased vascular density, capillary sprouting, and tortuosity compared to sham tissues exposed to sterile saline only. Tumor spheroids also induced the formation of lymphatic/blood vessel connections and LYVE-1-negative protrusions emerging from lymphatic vessels.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Overall, this study underscores the use of in vivo modeling to aid in the discovery of novel vascul","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"63-77"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864764","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":"Rivaroxaban as a Protector of Oxidative Stress-Induced Vascular Endothelial Glycocalyx Damage via the IQGAP1/PAR1-2/PI3K/Akt Pathway.","authors":"Lisa Kitasato, Minako Yamaoka-Tojo, Toshiyuki Iwaya, Yusuke Murayama, Yuki Ikeda, Takehiro Hashikata, Jun Oikawa, Machika Suzuki, Nonoka Misawa, Rei Kawashima, Fumihiro Ogawa, Junya Ako","doi":"10.1159/000542419","DOIUrl":"10.1159/000542419","url":null,"abstract":"<p><strong>Introduction: </strong>The vascular endothelial glycocalyx, crucial for blood vessel integrity and homeostasis, is vulnerable to oxidative stress, leading to endothelial dysfunction, which strongly correlates with cardiovascular disease (CVD). This study investigates the protective effects of rivaroxaban, a factor X inhibitor, on the glycocalyx under oxidative stress condition.</p><p><strong>Methods: </strong>We examined the impact of rivaroxaban on human umbilical vein endothelial cells exposed to acute and chronic H2O2-induced oxidative stress.</p><p><strong>Results: </strong>Rivaroxaban dose-dependently suppressed syndecan-1, a key component of the glycocalyx, shedding from cell surface, and enhanced protease-activated receptor (PAR)1-PAR2/phosphatidylinositol-3-kinase (PI3K)-dependent cell viability after acute induction of H2O2. This protective effect was linked to the translocation of IQGAP1, a scaffold protein that modulates the actin cytoskeleton, to the perinucleus from the cell membrane. Under chronic H2O2 treatments, rivaroxaban improves cell viability accompanied by an increase in hyaluronidase activities, aiding the turnover and remodeling of hyaluronic acid within the glycocalyx.</p><p><strong>Conclusion: </strong>We identify that rivaroxaban protects against oxidative stress-induced endothelial glycocalyx damage and cell viability through IQGAP1/PAR1-2/PI3K/Akt pathway, offering a potential to be a therapeutic target for CVD prevention.</p><p><strong>Introduction: </strong>The vascular endothelial glycocalyx, crucial for blood vessel integrity and homeostasis, is vulnerable to oxidative stress, leading to endothelial dysfunction, which strongly correlates with cardiovascular disease (CVD). This study investigates the protective effects of rivaroxaban, a factor X inhibitor, on the glycocalyx under oxidative stress condition.</p><p><strong>Methods: </strong>We examined the impact of rivaroxaban on human umbilical vein endothelial cells exposed to acute and chronic H2O2-induced oxidative stress.</p><p><strong>Results: </strong>Rivaroxaban dose-dependently suppressed syndecan-1, a key component of the glycocalyx, shedding from cell surface, and enhanced protease-activated receptor (PAR)1-PAR2/phosphatidylinositol-3-kinase (PI3K)-dependent cell viability after acute induction of H2O2. This protective effect was linked to the translocation of IQGAP1, a scaffold protein that modulates the actin cytoskeleton, to the perinucleus from the cell membrane. Under chronic H2O2 treatments, rivaroxaban improves cell viability accompanied by an increase in hyaluronidase activities, aiding the turnover and remodeling of hyaluronic acid within the glycocalyx.</p><p><strong>Conclusion: </strong>We identify that rivaroxaban protects against oxidative stress-induced endothelial glycocalyx damage and cell viability through IQGAP1/PAR1-2/PI3K/Akt pathway, offering a potential to be a therapeutic target for CVD prevention.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"22-36"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}