Vascular biology (Bristol, England)最新文献

{"title":"Under pressure: integrated endothelial cell response to hydrostatic and shear stresses.","authors":"Christian J Mandrycky, Takashi Ishida, Taylor Merkel, Samuel G Rayner, Adam M Heck, Brandon Hadland, Ying Zheng","doi":"10.1530/VB-25-0015","DOIUrl":"10.1530/VB-25-0015","url":null,"abstract":"<p><p>Blood flow within the vasculature is a critical determinant of endothelial cell (EC) identity and functionality, yet the intricate interplay of various hemodynamic forces and their collective impact on endothelial and vascular responses is not fully understood. Specifically, the role of hydrostatic pressure in the EC flow response is understudied, despite its known significance in vascular development and disease. To address this gap, we developed in vitro models to investigate how pressure influences EC responses to flow. Our study demonstrates that elevated pressure conditions significantly modify shear-induced flow alignment and increase EC density. Bulk and single-cell RNA sequencing analyses revealed that, while shear stress remains the primary driver of flow-induced transcriptional changes, pressure modulates shear-induced signaling in a dose-dependent manner. These pressure-responsive transcriptional signatures identified in human ECs were conserved during the onset of circulation in early mouse embryonic vascular development, where pressure was notably associated with transcriptional programs essential to arterial and hemogenic EC fates. Our findings suggest that pressure plays a synergistic role with shear stress on ECs and emphasize the need for an integrative approach to EC mechanotransduction, one that encompasses the effects induced by pressure alongside other hemodynamic forces.</p>","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12741814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145727613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylarginine levels and their impact on vascular aging: a systematic review.","authors":"Eduardo Eric Almeida do Carmo, Celia Cristina Diogo Ferreira, Roberta Melquiades Silva de Andrade","doi":"10.1530/VB-25-0004","DOIUrl":"10.1530/VB-25-0004","url":null,"abstract":"<p><p>Vascular aging is a multifactorial process characterized by structural and functional changes that compromise endothelial homeostasis and increase the risk of cardiovascular disease. Among the factors involved in this process, methylarginines, such as asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and NG-monomethyl-L-arginine (L-NMMA), stand out. These negatively modulate nitric oxide (NO) bioavailability, compromising endothelial function. This systematic review aimed to investigate the relationship between vascular aging and methylarginine levels, considering their influence on endothelial dysfunction and its impact on human health. The systematic search was conducted in scientific databases, resulting in the inclusion of four studies: three observational studies in humans and one experimental study in vitro. The findings demonstrated that elevated levels of ADMA, SDMA, and L-NMMA are associated with the progression of endothelial dysfunction, increased cardiovascular risk, and cognitive impairment in the elderly. The in vitro study reinforced this evidence by demonstrating that increasing concentrations of ADMA accelerate endothelial cell senescence, reduce telomerase activity, and decrease NO production. Interpretation of the results should consider the methodological limitations of the included studies, but the findings reinforce the role of methylarginines as potential biomarkers of vascular aging and highlight the need for further investigations exploring therapeutic strategies to minimize their deleterious effects.</p>","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12741813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145727675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"sFlt-1/PlGF and beyond: angiolymphatic-associated signatures and emerging biomarkers in placental pathology.","authors":"Seetu Palo, Mishu Mangla, Rohini Motwani","doi":"10.1530/VB-25-0009","DOIUrl":"10.1530/VB-25-0009","url":null,"abstract":"<p><p>The placenta is a highly vascularised organ that depends on tightly regulated angiolymphatic networks to sustain normal fetal growth and maternal adaptation to pregnancy. Disruption of these pathways contributes to major obstetric complications, including preeclampsia, fetal growth restriction, gestational diabetes, and stillbirth. In recent years, advances in molecular pathology and high-throughput technologies have identified a spectrum of angiogenic, lymphangiogenic, and endothelial biomarkers that provide mechanistic insights and hold translational promise. Among these, vascular endothelial growth factors (VEGF-A, VEGF-C, VEGF-D), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), angiopoietins, podoplanin, and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) have emerged as key regulators. Differential expression of these markers in placental tissue, maternal circulation, and extracellular vesicles has been correlated with disease severity, placental morphology, and adverse neonatal outcomes. Despite growing evidence, clinical application is limited by methodological heterogeneity, gestational age-specific variability, and incomplete understanding of lymphatic involvement in placental physiology. This review synthesises current knowledge on angiolymphatic biomarkers in the placenta, highlighting their role in vascular development, disease pathogenesis, and potential as diagnostic and prognostic tools. Future research integrating molecular assays, imaging modalities, and systems biology approaches is essential to standardise biomarker panels and translate them into clinically meaningful strategies for maternal-fetal medicine.</p>","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12697339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating endothelium-derived hyperpolarization, nitric oxide, and prostacyclin pathways: the multimodal potential of human tissue kallikrein-1.","authors":"Paolo Madeddu, Styliani Goulopoulou, David Wambeke","doi":"10.1530/VB-25-0006","DOIUrl":"10.1530/VB-25-0006","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>Endothelial cells regulate vascular tone by releasing nitric oxide (NO) and prostacyclin (PGI2), as well as by initiating hyperpolarization of vascular smooth muscle cells through K+ channels and myoendothelial coupling. This review highlights the therapeutic potential of targeting endothelium-dependent hyperpolarization (EDH) to address unmet needs in microvascular disorders such as cerebral small vessel disease, an important cause of stroke and dementia, and preeclampsia, a major pregnancy complication associated with maternal and fetal morbidity. Oxidative stress, connexin dysfunction, and impaired K+ channel signaling disrupt electrical coupling between endothelium and smooth muscle cells, leading to loss of vascular homeostasis. Building on this mechanistic convergence, we propose a multimodal therapeutic strategy to restore EDH in concert with the NO and PGI2 pathways. Within this framework, human tissue kallikrein-1 (KLK1) exemplifies an integrated therapeutic approach by simultaneously engaging multiple endothelial vasodilator mechanisms. Through bradykinin B2 receptor signaling, KLK1 enhances NO and PGI2 production while also promoting EDH via K+ channel activation. Its recombinant form, rinvecalinase alfa (DM199), has demonstrated consistent benefit in early-phase clinical trials, supporting its potential to restore endothelial balance. By reactivating these complementary vasodilatory pathways, DM199 improves microvascular perfusion and endothelial resilience, positioning it as a prototype multimodal therapy for microvascular diseases.</p><p><strong>Key message: </strong>Restoring endothelium-derived hyperpolarization alongside NO and prostacyclin signaling represents a promising multimodal approach to treat endothelial dysfunction and microvascular disorders.</p>","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12631013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145460866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATF6 inhibition suppresses the protective effects of pasireotide in human and bovine endothelial cells.","authors":"Saikat Fakir, Md Matiur Rahman Sarker, Madan Sigdel, Nektarios Barabutis","doi":"10.1530/VB-25-0003","DOIUrl":"10.1530/VB-25-0003","url":null,"abstract":"<p><p>Activating transcription factor 6 (ATF6) is an unfolded protein response sensor with a significant role in endothelial integrity and barrier function. This study investigates the effects of Ceapin-A7, which is an ATF6 inhibitor, in mediating the protective effects of pasireotide (PAS) in the endothelium. Ceapin-A7 suppressed PAS-induced glucose-regulated protein 94 (GRP94) augmentation, cofilin deactivation, and MLC2 dephosphorylation. Furthermore, ATF6 inhibition counteracted the anti-oxidative and anti-inflammatory effects of PAS in human and bovine lung endothelial cells, as evidenced by increased ROS generation and suppression of pSTAT1, pSTAT3, pERK1/2, and pP38. Our study adds information on the protective actions of pasireotide in endothelial cells and supports ongoing efforts to enrich our knowledge of the pathophysiology of sepsis and lung injury.</p>","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipocalin 2 deficiency impacts angiogenesis after ischemia in vivo and in vitro.","authors":"L Zhang, Z Aref, H A B Peters, M R de Vries, A Y Nossent, P H A Quax","doi":"10.1530/VB-25-0001","DOIUrl":"10.1530/VB-25-0001","url":null,"abstract":"<p><p>Therapeutic neovascularization is a promising therapy option for patients with peripheral arterial disease. We followed in time the gene expression after induction of hind limb ischemia in mice with different patterns of blood flow restoration and identified lipocalin 2 (LCN2) as a strongly upregulated factor whose role in neovascularization deserves further investigation. In this study, we investigated the role of LCN2 in angiogenesis using the hind limb ischemia (HLI) model, ex vivo angiogenic aortic ring assay, and by assessing the pre-existing collaterals in the pial circulation in both Lcn2 -/- mice and wild-type (WT) mice. This demonstrated an upregulated mRNA expression of Lcn2 after HLI and reduced post-ischemic angiogenesis in Lcn2 -/- compared to WT mice. In the aortic ring assay, angiogenic sprouting was decreased in Lcn2 -/- compared to WT mice. The blood flow recovery and arteriogenesis after HLI and preexisting collateral density in the pial circulation were similar in Lcn2 -/- and WT mice. In vitro, siRNA-mediated LCN2 knockdown impaired HMVEC migration and tube formation. These results show that LCN2 is a potential pro-angiogenic factor and that LCN2 downregulation has a negative effect on angiogenesis in vivo and in vitro.</p>","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological and immunohistochemical characterization of dopamine D4 receptor in human umbilical artery and vein.","authors":"Pedro Renato Guazzelli, José Britto-Júnior, Pérola Rafaella Cedano Godoy P Souza, Vinicius Francisco Cardoso, Antonio Tiago Lima, Felipe Caliani Mathias Netto, Valéria Barbosa de Souza, Edson Antunes, André Schenka, Gilberto De Nucci","doi":"10.1530/VB-24-0010","DOIUrl":"10.1530/VB-24-0010","url":null,"abstract":"<p><p>To investigate the effects of the dopamine D4 receptor agonist A-412997 and the D4 antagonist sonepiprazole in human isolated umbilical artery (HUA) and vein (HUV) and the expression of the D4 receptor by immunohistochemistry in these vessels. A segment of the umbilical cord (10-20 cm) from the insertion point in the placenta and 5 cm from the umbilicus was removed by the obstetrician and placed in a container with Krebs-Henseleit solution (KHS). The Wharton's jelly was removed, and HUA and HUV rings (3 mm) were suspended in 10 mL organ baths containing oxygenated (95% O2:5% CO2) and heated (37 °C) KHS. For immunohistochemistry, the vessels were fixed in 10% formalin, embedded in paraffin wax and sectioned (4 µm). A-412997 did not induce contractions in the HUA rings. In HUA pre-contracted rings, A-412997 induced concentration-dependent relaxations, which were reduced when the HUA rings were pre-incubated with L-NAME. A-412997 caused concentration-dependent contractions of HUV rings, which were potentiated by pre-treatment with L-NAME and reduced by pre-incubation with 6-nitrodopamine. In HUV pre-contracted rings, A-412997 failed to induce relaxations. Sonepiprazole antagonized A-412997-induced contractions in HUV rings and provoked concentration-dependent relaxations in pre-contracted HUA and HUV rings. Dopamine D4 receptor was positive in both HUA and HUV, especially in the endothelium, and detected only in HUV smooth muscle cells. Activation of HUA D4 receptor is associated with relaxation, whereas in HUV, it leads to contraction. Differential expression of D4 receptors may modulate umbilical-placental blood flow.</p>","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum tissue plasminogen activator after cycling with blood flow restriction.","authors":"Josh B Landers, Melissa Allen, Ibrahim Oladele, Leah Lowe, Nawab Ali, Jacquie Rainey, James Fletcher, Korben Landers","doi":"10.1530/VB-24-0008","DOIUrl":"10.1530/VB-24-0008","url":null,"abstract":"<p><p>Blood flow restriction exercise (BFRE) is a therapeutic approach traditionally used to facilitate muscular strength and hypertrophy. Emerging evidence has identified its benefits on other systems and metabolic processes. The emphasis of this study was to examine potential impact of BFRE on serum levels of tissue plasminogen activator (tPA). Eighteen healthy adults (nine males, nine females; mean age: 34.44 ± 9.97) were randomized into groups to perform cycling either with or without blood flow restriction (BFR). Blood samples were collected before and after exercise to analyze serum concentrations of tPA. Significance in tPA between exercise groups did not reach significance but did show a large effect size (0.14) in favor of the BFR group. The trend suggests that this study was underpowered to reach significance. Further research should continue examining the impact of BFRE on serum levels of tPA. This methodology could be adapted to other populations to increase generalizability of results.</p>","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protection of liver sinusoidal endothelial cells using different preservation solutions.","authors":"Julia H E Houtzager, Anne-Marieke van Stalborch, Charlotte Hofstee, Thomas M van Gulik, Jaap D van Buul","doi":"10.1530/VB-24-0004","DOIUrl":"10.1530/VB-24-0004","url":null,"abstract":"<p><p>Donor liver preservation methods and solutions have evolved over the last years. Liver sinusoidal endothelial cell (LSEC) barrier function and integrity during preservation are crucial for outcomes of liver transplantation. Therefore, the present study aimed to determine optimal preservation of LSEC barrier function and integrity using different preservation solutions. Human umbilical vein endothelial cells (HUVECs) and LSECs were incubated in either University of Wisconsin machine perfusion solution (UW-MPS), histidine-tryptophan-ketoglutarate, or endothelial cell growth medium 2 (EGM2) (as a gold standard for cell culturing). Endothelial integrity was assessed by measurement of cellular morphology and expression of membrane proteins: PECAM-1, ICAM-1 and Fc-gamma receptor CD32b (FcΥRCD32b). Endothelial barrier function was measured by electric cell-substrate impedance sensing. Cellular response to inflammatory stimuli with tumor necrosis factor-alpha (TNF-α) was tested by studying trans-endothelial migration (TEM) under flow conditions. Differences in these parameters were analyzed between the different preservation solutions. PECAM-1 expression was high for all preservation solutions in HUVECs and LSECs. ICAM-1 expression was increased in both LSECs and HUVECs in all preservation solutions plus TNF-α. UW reduced PECAM-1 expression, whereas EGM2 medium promoted barrier function in LSECs and HUVECs, and monolayer recovery after wounding was best achieved in cells incubated in EGM2. LSECs and HUVECs incubated with EGM2 plus TNF-α both supported neutrophil adhesion and TEM, but much less to none when incubated in UW plus TNF-α. Overall, EGM2 showed the best results in preserving endothelial barrier function for both HUVECs and LSECs.</p>","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lack of intracranial atherosclerosis in various atherosclerotic mouse models.","authors":"Diewertje I Bink, Katja Ritz, Claire Mackaaij, Olga Stam, Sanny Scheffer, Mark R Mizee, Hanneke J Ploegmakers, Bert J van Het Hof, Onno J de Boer, Judith C Sluimer, Guido R Y De Meyer, Louise van der Weerd, Helga E de Vries, Mat J A P Daemen","doi":"10.1530/VB-23-0013","DOIUrl":"10.1530/VB-23-0013","url":null,"abstract":"<p><p>Although mice are used extensively to study atherosclerosis of different vascular beds, limited data are published on the occurrence of intracranial atherosclerosis. Since intracranial atherosclerosis is a common cause of stroke and is associated with dementia, a relevant animal model is needed to study these diseases. We examined the presence of intracranial atherosclerosis in different atherogenic mouse strains and studied differences in vessel wall characteristics in mouse and human tissue in search of possible explanations for the differing atherosclerotic susceptibility between extracranial and intracranial vessels. The presence of atherosclerotic plaques was systematically examined from the distal common carotids to the circle of Willis in three atherogenic mouse models. Extra- and intracranial vessel characteristics were studied by immunohistochemistry. All three strains developed atherosclerotic lesions in the common carotids, while no lesions were found intracranially. This coincided with altered vessel morphology. Compared to extracranial sections, intracranially the number of elastic layers decreased, tight junction markers increased, and antioxidant enzyme heme oxygenase (HO)-1 increased. Higher HO-1 expression was also shown in human intracranial arteries. Human brain endothelial cell stimulation with oxidized LDL induced endogenous protective antioxidant HO-1 levels through NRF2 translocation. Intracranial atherosclerosis was absent in three atherogenic mouse models. Intracranial vessel segments showed an increased presence of junction markers in mice and increased HO-1 in both mice and human tissue. We suggest that differences in brain vessel structure and induced antioxidant levels in the brain endothelium found in mouse and human tissue may contribute to the decreased atherosclerosis susceptibility of intracranial arteries.</p>","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}