Journal of Vascular Research最新文献

{"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":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965820/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A State-Wide Retrospective Cohort Study Examining Effects of Transfusing Old Blood Products in Vascular Surgical Patients.","authors":"Nchafatso Obonyo, Lawrence Lu, Zohaib Nadeem, Zahra Hosseinzadeh, Reema Rachakonda, Nicole White, Declan Sela, Matthew Tunbridge, Beatrice Sim, Louise See Hoe, Yogeesan Sivakumaran, Gianluigi Li Bassi, Jonathon Fanning, John-Paul Tung, Jacky Suen, John Fraser","doi":"10.1159/000548049","DOIUrl":"10.1159/000548049","url":null,"abstract":"<p><p><p>Introduction: We investigated the effects of transfusing blood products close to the expiration date (i.e., ≥35 days packed red blood cells [PRBCs] and >3 days platelets [PLTs]) on vascular patients.</p><p><strong>Methods: </strong>We retrospectively examined all PRBC and PLT transfusions in patients who underwent vascular procedures without cardiopulmonary bypass in Queensland from 2007 to 2013. Mortality, length of stay (LOS), and blood product quantities were compared in patients transfused exclusively with PRBCs <21 days vs. PRBCs ≥35 days and PLTs ≤3 days vs. PLTs >3 days.</p><p><strong>Results: </strong>No significant mortality difference was found between patients transfused fresh vs. old PRBCs (26/493 [5.3%] vs. 6/152 [3.9%]; OR 0.75; 95% CI: 0.3-1.9). Patients transfused fresh PRBCs experienced a longer LOS (11 days [IQR: 7-20] vs. 10 days [IQR: 7-15]; 95% CI: -4.8 to -0.24) and more PRBC units (3.9 ± 4.5 units vs. 2.1 ± 1.3 units; 95% CI: -2.3 to -0.9). Among patients transfused PLTs, there were no significant differences in mortality (24/124 [19.4%] vs. 14/78 [17.9%]; OR 1.0; 95% CI: 0.5-2.3) between patients transfused fresh vs. old PLTs.</p><p><strong>Conclusion: </strong>Within the limitations of the retrospective study design, transfusion of older PRBCs or PLTs was associated with fewer transfused units, shorter hospital stays, but no difference in mortality. </p>.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"304-311"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959259","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":"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":"121-132"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136606/pdf/","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":"OA","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":"Chick Chorioallantoic Membrane as an in vivo Model for the Study of Angiogenesis and Lymphangiogenesis.","authors":"Zhenzhen Wan, Christoph Hirche, Fabia Fricke, Adrian Dragu, Patrick A Will","doi":"10.1159/000542875","DOIUrl":"10.1159/000542875","url":null,"abstract":"<p><strong>Background: </strong>The high incidence of vascular and lymphatic metastasis is closely associated with poor prognosis and mortality in cancer. Finding effective inhibitors to prevent pathological angiogenesis and lymphangiogenesis relies on appropriate in vivo models. The chick embryo chorioallantoic membrane (CAM) is formed by the fusion of the chorion and allantois during embryonic development.</p><p><strong>Summary: </strong>In this context, we primarily summarize the changes in vascular and lymphatic vessel formation in tumors under the action of drugs using this model, providing a preclinical model basis for effective tumor inhibitors.</p><p><strong>Key messages: </strong>Due to natural immunological defects, chick embryos accept various tissue and species transplants without immune response. The CAM model has been widely used in studying angiogenesis, antiangiogenesis, tumor growth, tumor metastasis, and drug efficacy. This review describes the use of CAM assays as a valuable method for testing the in vivo effects of drugs on vascular and lymphatic vessel formation before further investigating the effects of drugs on tumor vessels and lymphatic vessels in animal models.</p><p><strong>Background: </strong>The high incidence of vascular and lymphatic metastasis is closely associated with poor prognosis and mortality in cancer. Finding effective inhibitors to prevent pathological angiogenesis and lymphangiogenesis relies on appropriate in vivo models. The chick embryo chorioallantoic membrane (CAM) is formed by the fusion of the chorion and allantois during embryonic development.</p><p><strong>Summary: </strong>In this context, we primarily summarize the changes in vascular and lymphatic vessel formation in tumors under the action of drugs using this model, providing a preclinical model basis for effective tumor inhibitors.</p><p><strong>Key messages: </strong>Due to natural immunological defects, chick embryos accept various tissue and species transplants without immune response. The CAM model has been widely used in studying angiogenesis, antiangiogenesis, tumor growth, tumor metastasis, and drug efficacy. This review describes the use of CAM assays as a valuable method for testing the in vivo effects of drugs on vascular and lymphatic vessel formation before further investigating the effects of drugs on tumor vessels and lymphatic vessels in animal models.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"109-120"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877649","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":"Erratum.","authors":"","doi":"10.1159/000545807","DOIUrl":"10.1159/000545807","url":null,"abstract":"","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"232"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120131","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":"AKAP12 Variant 1 Knockout Enhances Vascular Endothelial Cell Motility.","authors":"Ashrifa Ali, Bhaskar Roy, Micah B Schott, Bryon D Grove","doi":"10.1159/000547350","DOIUrl":"10.1159/000547350","url":null,"abstract":"<p><strong>Introduction: </strong>Previous work indicates that AKAP12 is expressed in endothelial cells as two variants and may play a role in cell motility. However, the role of each variant in cell motility is unknown; therefore, this study investigated the role of AKAP12 in endothelial cell motility with a specific focus on AKAP12 variants, AKAP12v1 and AKAP12v2.</p><p><strong>Methods: </strong>AKAP12 expression levels in cultured endothelial cells were determined by Western blotting and immunofluorescence microscopy. AKAP12 knockdown and AKAP12 variant knockout were done using antisense oligonucleotide and siRNA treatment and CRISPR/Cas9 knockout, respectively. The effect of AKAP12 variant knockout was further analyzed by RNA-seq.</p><p><strong>Results: </strong>AKAP12 expression was cell density-dependent, with the highest expression in subconfluent cultures and lowest in confluent cultures. AKAP12 expression was also elevated in cells at the wound edge of wounded endothelial cell monolayers. Knockdown of both variants inhibited cell migration, but CRISPR/Cas9 knockout of AKAP12v1 enhanced migration. RNA-seq revealed that loss of AKAP12v1 affected genes associated with cell migration and intercellular junctions.</p><p><strong>Conclusion: </strong>We propose that AKAP12v1 and AKAP12v2 play distinct yet complementary roles in endothelial cell migration and likely work together in controlling the signaling events associated with vascular repair and development.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"312-329"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675130","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}

{"title":"Functional Adaptations in Coronary Reactivity following Healthy Pregnancy in Swine.","authors":"Selina M Tucker, Salman I Essajee, Cooper M Warne, Gregory M Dick, Styliani Goulopoulou, Johnathan D Tune","doi":"10.1159/000543116","DOIUrl":"10.1159/000543116","url":null,"abstract":"<p><strong>Introduction: </strong>This study was designed to test the hypothesis that coronary artery adaptations during the postpartum period are related to underlying reductions in endothelium-dependent relaxation and/or augmented smooth muscle vasoconstrictor responsiveness.</p><p><strong>Methods: </strong>In vivo experiments were performed in control (nonpregnant) and postpartum swine 35-45 days of postdelivery, with isometric tension experiments performed in isolated coronary arteries from those animals.</p><p><strong>Results: </strong>Coronary artery rings demonstrated increases in active tension generation following incremental increases in passive stretch with no differences between groups. Endothelium-dependent relaxation to bradykinin was attenuated in arteries from postpartum swine versus control (p < 0.005). Concentration-dependent contractions to the thromboxane A2 mimetic U46619 (0.1 n<sc>m</sc>-1 µ<sc>m</sc>) were shifted rightward (EC50 27 ± 10 n<sc>m</sc> vs. 238 ± 66 n<sc>m</sc>; p < 0.01) in arteries from postpartum swine, with no changes in maximum contractile responses (p = 0.68). Intracoronary administration of U46619 (1 n<sc>m</sc>-1 µ<sc>m</sc>) in open-chest swine decreased coronary blood flow ∼45 ± 3% in nonpregnant controls but had no effect on coronary blood flow in postpartum swine. Concentration-dependent contractions to KCl (5-90 m<sc>m</sc>) showed a rightward shift in arteries from postpartum swine (15.6 ± 1.4 m<sc>m</sc> vs. 21.8 ± 1.9 m<sc>m</sc>; p = 0.03), with no change in maximum response. Taken together, the postpartum period is associated with reduced endothelium-dependent relaxation and responsiveness to receptor-dependent and -independent vasoconstrictor stimuli.</p><p><strong>Conclusion: </strong>These findings indicate that chronic exposure of the coronary circulation to the pregnancy/postpartum milieu results in functional adaptations in sensitivity to paracrine/hormonal compounds that should be further explored.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"78-87"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813667","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}