Journal of Vascular Research最新文献

{"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":"https://doi.org/10.1159/000543322","url":null,"abstract":"<p><p>Aortic aneurysm (AA) is clinically important, but its causes remain unclear. Smoking is consistently linked to AA, while diabetes shows a negative association despite being a risk factor for atherosclerosis. Biomechanical and histological studies of the aortic wall may provide insights. In our study, 75 rats were divided into control, smoker, diabetic, and diabetic smoker groups. After exposure to smoking and diabetes induction, thoracic aorta samples were collected. Biomechanical tests showed lower resistance in diabetic smokers compared to smokers alone. Histological analysis revealed no significant differences in collagen, elastic fibers, or inflammation. Metalloproteinase-9 (MMP-9) activity also showed no significant variation. Despite risk factors, the thoracic aorta may be resilient to aneurysm development, as indicated by its biomechanical properties.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"1-22"},"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":"https://doi.org/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 aims 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 (VSMC) 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 are 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":"1-18"},"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":"https://doi.org/10.1159/000544029","url":null,"abstract":"<p><p>Vascular smooth muscle cell proliferation and vascular homeostasis is thought to be regulated by nitric oxide and prostaglandins. We examined the effect of exogenous linsidomine, a NO releasing compound, in a model of balloon injury iliac arteries of rabbits. On the cellular levels NO can exert effects like cellular survival, growth and proliferation inhibition. Smooth muscle cell (SMC) proliferation was quantified as change of intima-media-ratio. Linsidomine injection or its vehicle was performed with an infusion-balloon catheter directly into the vessel wall. Balloon angioplasty resulted in a significant increase of intima-media-ratio during three weeks. Linsidomine treatment decreased the intima media ratio significantly (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. In in vitro experiments linsidomine inhibited significantly and dose-dependently rabbit smooth muscle cell proliferation measured by BrdU incorporation. Further linsidomine increased rate of apoptotic SMC's, however this effect was p53 independent. 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. Despite single administration, local application of linsidomine resulted in potent inhibition of intima proliferation.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"1-19"},"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":"https://doi.org/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 (SS) rats on normal diet. Masson Trichrome (MT) and Verhoeff Van Gieson (VVG) 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).  Results: 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":"1-23"},"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":"https://doi.org/10.1159/000542728","url":null,"abstract":"<p><strong>Introduction: </strong>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 down-regulated 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 increased smad7 in AMI rats. Atorvastatin induced the down-regulation 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":"1-22"},"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":"Fibrillin-1 Deficiency Perturbs Aortic Cholinergic Relaxation and Adrenergic Contraction in a Mouse Model of Early Onset Progressively Severe Marfan Syndrome.","authors":"Anna Cantalupo, Keiichi Asano, Sergey Dikalov, Dylan Gordon, Francesco Ramirez","doi":"10.1159/000542481","DOIUrl":"10.1159/000542481","url":null,"abstract":"<p><strong>Introduction: </strong>The pathogenic role of nitric oxide (NO) signaling during development of thoracic aortic aneurysm (TAA) in Marfan syndrome (MFS) is currently unclear. We characterized vasomotor function and its relationship to the activity of the NO-generating enzymes in mice with early onset progressively severe MFS.</p><p><strong>Methods: </strong>Wire myography, immunoblotting, measurements of aortic NO, and superoxide levels were used to compare vasomotor function, contractile protein levels, and the activity of endothelial and inducible NO synthase (eNOS and iNOS, respectively) in ascending thoracic aortas of Fbn1mgR/mgR mice relative to wild-type littermates.</p><p><strong>Results: </strong>Isometric force measurements of aortic rings from 16-day-old male Fbn1mgR/mgR mice revealed a significant reduction in acetylcholine-induced relaxation and increased phenylephrine (PE)-promoted contractility, associated with abnormally low eNOSSer1177 phosphorylation, decreased NO production, and augmented superoxide levels. Greater aortic contractility was associated with α1-adrenoceptor upregulation and normal levels of contractile proteins. While iNOS inhibition had no effect on vasomotor functions, mutant aortic rings preincubated with a nonspecific NOS inhibitor yielded a greater PE response, implying a significant contribution of endothelial dysfunction to aortic hypercontractility.</p><p><strong>Conclusion: </strong>Impaired eNOS signaling disrupts aortic cholinergic relaxation and adrenergic contraction in MFS mice with dissecting TAA.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"1-13"},"PeriodicalIF":1.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007751","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}

{"title":"Characterising the Time Course of the Dilatory Response of Healthy Retinal Arteries during Flicker-Light Provocation.","authors":"Robert J Summers, Rebekka Heitmar","doi":"10.1159/000541443","DOIUrl":"10.1159/000541443","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The dilatory response of healthy retinal arterioles to flicker-light (FL) provocation appears to be biphasic. The vessel diameter rapidly increases (acute phase) over 5-10 s, then barely increases thereafter (maintenance phase) until FL cessation. This reaction is usually characterised at a single point by two parameters: maximum dilation (MD) relative to baseline diameter (MD, %) and time to MD (RT, s). This paper describes the biphasic reaction of retinal arteries during FL provocation using a bi-linear function.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Retinal arterioles from 45 adults were examined during flicker provocation. Each individual time course of arterial diameter change during FL provocation was characterised by a bi-linear equation and compared with MD and RT.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Slopes of the acute phase were 0.506%/s, and the maintenance phase was nearly flat (0.012%/s). The mean time at which the reaction changed from acute to maintenance phase was 7.4 s which is significantly different from RT (16.0 s). Mean dilation at this point (2.987%) was significantly different from MD (3.734%), but it was still 80% of MD in less than half of RT.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Bi-linear fitting parameters better characterises the arterial dilatory response than MD and RT. Further stratification of clinical groups using bi-linear fitting may provide insight of the underlying physiology of vessel dilation for different pathologies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The dilatory response of healthy retinal arterioles to flicker-light (FL) provocation appears to be biphasic. The vessel diameter rapidly increases (acute phase) over 5-10 s, then barely increases thereafter (maintenance phase) until FL cessation. This reaction is usually characterised at a single point by two parameters: maximum dilation (MD) relative to baseline diameter (MD, %) and time to MD (RT, s). This paper describes the biphasic reaction of retinal arteries during FL provocation using a bi-linear function.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Retinal arterioles from 45 adults were examined during flicker provocation. Each individual time course of arterial diameter change during FL provocation was characterised by a bi-linear equation and compared with MD and RT.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Slopes of the acute phase were 0.506%/s, and the maintenance phase was nearly flat (0.012%/s). The mean time at which the reaction changed from acute to maintenance phase was 7.4 s which is significantly different from RT (16.0 s). Mean dilation at this point (2.987%) was significantly different from MD (3.734%), but it was still 80% of MD in less than half of RT.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Bi-linear fitting parameters better characterises the arterial dilatory response than MD and RT. Further stratification of clinical groups using bi-linear fitting may provide insight of the underlying physiology of vessel dilation for different pa","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"1-9"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676032","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}

{"title":"Microvesicles Derived from Nitric Oxide Synthase-Inhibited Endothelial Cells Promote Cell Dysfunction.","authors":"Vinicius P Garcia, Kelly A Stockelman, Ma'ayan V Levy, Hannah K Fandl, Anabel Goulding, Jamie G Hijmans, Samuel T Ruzzene, Auburn R Berry, Jared J Greiner, Christopher A DeSouza","doi":"10.1159/000542280","DOIUrl":"10.1159/000542280","url":null,"abstract":"<p><strong>Introduction: </strong>The aims of this study were to determine (1) whether endothelial nitric oxide synthase (eNOS) inhibition stimulates endothelial microvesicles (EMVs) release and (2) the effect of EMVs derived from eNOS-inhibited cells on endothelial cell eNOS, inflammation, apoptosis, and tissue-type plasminogen activator (t-PA).</p><p><strong>Methods: </strong>Human umbilical vein endothelial cells (HUVECs) were treated with the eNOS inhibitor (NG-nitro-<sc>l</sc>-arginine methyl ester [L-NAME], 300 µ<sc>M</sc>) for 24 h. EMVs from untreated and L-NAME-treated cells were isolated, quantified, and exposed to HUVECs for 24 h.</p><p><strong>Results: </strong>eNOS-inhibited cells released significantly higher EMVs than untreated cells (81 ± 13 vs. 41 ± 15 EMV/μL; p = 0.005). Expression of total eNOS (97.1 ± 16.4 vs. 157.5 ± 31.2 arbitrary units [AUs]; p = 0.01), p-eNOS (4.9 ± 1.2 vs. 9.1 ± 12.6 AUs; p = 0.02), and NO production (5.0 ± 0.8 vs. 7.0 ± 1.3 µmol/L; p = 0.04) were significantly lower in cells treated with EMVs from L-NAME-treated cells. L-NAME-derived EMVs induced significantly higher IL-6 (38.3 ± 10.3 vs. 21.0 ± 3.8 pg/mL; p = 0.01) and IL-8 (38.9 ± 7.0 vs. 27.2 ± 6.2 pg/mL; p = 0.04) production concurrent with higher expression of p-NF-κB p65 (Ser536) (9.7 ± 1.6 vs. 6.1 ± 1.2 AUs; p = 0.01). Expression of activated caspase-3 was higher (9.5 ± 1.1 vs. 6.4 ± 0.4 AUs) and t-PA lower (24.2 ± 4.3 vs. 36.2 ± 8.4 AUs; p = 0.04) in cells treated with L-NAME-derived EMVs.</p><p><strong>Conclusion: </strong>eNOS inhibition induces an increase in EMV release and an EMV phenotype with adverse cellular effects.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"10-21"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807585","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}