Microvascular research最新文献

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Effect of pharmacologic mydriasis on blood flow across different retinal regions measured by laser speckle contrast imaging in healthy adults. 激光散斑对比成像对健康成人不同视网膜区域血流的影响。
IF 2.9 4区 医学
Microvascular research Pub Date : 2026-10-19 DOI: 10.1016/j.mvr.2026.105028
Lian Duan, Xiaogang Wang, Giovana Rosa Gameiro, Xiaoming Wang, Shuya Wang, Andrew Hoover, Hong Jiang, Jianhua Wang
{"title":"Effect of pharmacologic mydriasis on blood flow across different retinal regions measured by laser speckle contrast imaging in healthy adults.","authors":"Lian Duan, Xiaogang Wang, Giovana Rosa Gameiro, Xiaoming Wang, Shuya Wang, Andrew Hoover, Hong Jiang, Jianhua Wang","doi":"10.1016/j.mvr.2026.105028","DOIUrl":"10.1016/j.mvr.2026.105028","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the effect of pharmacologic mydriasis on different retinal regions using laser speckle contrast imaging (LSCI; XyCAM CRE) in healthy adults.</p><p><strong>Methods: </strong>In this prospective, self-controlled study, 16 healthy adults (32 eyes) underwent same-day retinal imaging before and after pharmacologic dilation. One nondominant eye was dilated, and the fellow eye served as a control. Both eyes were imaged at each session. Macular regions of interest (ROIs) included the overall field of view (FOV), foveal avascular zone (FAZ), and perifoveal region (PFR). Optic nerve head (ONH) ROIs included the FOV, optic disc (OD), disc perfusion (DP), disc vessels (DV), and temporal peripapillary region (TPPR). Heart rate-adjusted blood flow velocity index (BFVi) metrics were analyzed by a masked grader. Differences were assessed using paired tests with false discovery rate (FDR) correction for multiple comparisons.</p><p><strong>Results: </strong>In dilated eyes, six of nine macular BFVi parameters increased significantly after mydriasis and remained significant after FDR correction (adjusted P = 0.020-0.047). In the ONH, significant increases were observed only for FOV-based BFVi parameters (adjusted P = 0.024-0.049), whereas measurements within the OD, DP, DV, and TPPR regions showed no significant changes (all adjusted P > 0.05). No significant changes were detected in fellow control eyes in either region (all adjusted P > 0.05).</p><p><strong>Conclusions: </strong>Pharmacologic mydriasis was associated with increased BFVi measurements on LSCI, particularly in the macular region, where multiple BFVi parameters remained significant after multiple-comparison correction. The comparatively limited changes observed within the ONH suggest regional differences in retinal vascular responses to mydriatic agents and highlight the importance of accounting for pupil status when interpreting quantitative retinal perfusion measurements. These findings provide insight into the influence of pharmacologic dilation on retinal microvascular perfusion measurements and may help standardize LSCI-based imaging protocols in clinical and research settings.</p>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":" ","pages":"105028"},"PeriodicalIF":2.9,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224488","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}
引用次数: 0
Assessment of endothelial glycocalyx degradation in sepsis using direct visualization with sublingual microscopy. 使用舌下显微镜直接可视化评估脓毒症中内皮糖萼降解。
IF 2.9 4区 医学
Microvascular research Pub Date : 2026-10-19 DOI: 10.1016/j.mvr.2026.105029
John H Lee, Kaori Oshima, Michael J Massey, Derek C Angus, Donald M Yealy, Eric P Schmidt, Nathan I Shapiro
{"title":"Assessment of endothelial glycocalyx degradation in sepsis using direct visualization with sublingual microscopy.","authors":"John H Lee, Kaori Oshima, Michael J Massey, Derek C Angus, Donald M Yealy, Eric P Schmidt, Nathan I Shapiro","doi":"10.1016/j.mvr.2026.105029","DOIUrl":"https://doi.org/10.1016/j.mvr.2026.105029","url":null,"abstract":"<p><strong>Background: </strong>The endothelial glycocalyx plays a crucial role in the pathophysiology of sepsis, but assessment of glycocalyx injury in clinical settings remains challenging. Perfused boundary region (PBR) is derived from sublingual intravital video microscopy and has been studied as a surrogate of endothelial glycocalyx barrier function. The goal of this study was to determine whether PBR is associated with circulating heparan sulfate (a biochemical marker of glycocalyx degradation), sepsis status, in-hospital mortality, and intravenous (IV) fluid administration.</p><p><strong>Methods: </strong>This was an ancillary study to the randomized clinical trial Protocol-Based Care for Early Septic Shock (ProCESS). The patients were enrolled from six hospitals and controls from two hospitals. Subjects underwent sublingual microscopy. We assessed the association between PBR and heparan sulfate levels. We also compared the baseline PBR between sepsis and non-infected controls, and between the survivors and non-survivors. Lastly, the association between IV fluid administration and PBR was assessed using a linear mixed-effects model.</p><p><strong>Results: </strong>A total of 193 subjects were included: 144 had septic shock and the in-hospital mortality rate was 12.5%. The PBR was associated with levels of circulating heparan sulfate (r = 0.32, R<sup>2</sup> = 0.10, p = 0.02). The baseline PBR was higher in sepsis compared to controls (2.29 ± 0.40 vs. 2.02 ± 0.41, p < 0.01) but not different between survivors and non-survivors. PBR was also not associated with IV fluid administration volume.</p><p><strong>Conclusions: </strong>Findings suggest a link between PBR and endothelial glycocalyx degradation observed in sepsis.</p>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":" ","pages":"105029"},"PeriodicalIF":2.9,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224517","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}
引用次数: 0
Integrated experimental and theoretical approaches to microvascular transport and regulation 综合实验和理论方法的微血管运输和调控编辑微血管功能:实验和计算的观点。
IF 2.7 4区 医学
Microvascular research Pub Date : 2026-07-01 Epub Date: 2026-03-06 DOI: 10.1016/j.mvr.2026.104931
Peter Balogh , Osama Harraz
{"title":"Integrated experimental and theoretical approaches to microvascular transport and regulation","authors":"Peter Balogh ,&nbsp;Osama Harraz","doi":"10.1016/j.mvr.2026.104931","DOIUrl":"10.1016/j.mvr.2026.104931","url":null,"abstract":"<div><div>The microcirculation is in a continuous state of change as we grow and evolve in both health and disease. The transport characteristics of blood flow through the microcirculation, intercellular signaling in response to local demands, and coordination between these two players strongly influence the adaptation of the microcirculation to support microvascular function. Notably, both biophysical and electrophysiological phenomena contribute to processes which influence new blood vessel growth and adaption, local regulation of vascular tone and control of microvascular blood distribution, or pathologies related to tumor growth or organ dysfunction. High resolution computational models and experimental studies promise to provide new insights into the mechanisms underlying such processes.</div><div>This special issue focuses on i) computational models which elucidate hemodynamic characteristics unique to the microcirculation, ii) elucidating microvascular signaling related to blood flow regulation and distribution, and iii) integrating hemodynamics and intercellular signaling to identify synergistic roles and mechanistic contributions.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"166 ","pages":"Article 104931"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372929","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}
引用次数: 0
Retinal structural and vascular alterations in diabetic kidney disease: A bidirectional Mendelian randomization study 糖尿病肾病视网膜结构和血管改变:一项双向孟德尔随机研究
IF 2.7 4区 医学
Microvascular research Pub Date : 2026-07-01 Epub Date: 2026-03-03 DOI: 10.1016/j.mvr.2026.104928
Shulei Man , Kefan Mou , Yifan Zhang , Yuzhu Gao , Xue Wu , Hanyue Xu , Ming Zhang
{"title":"Retinal structural and vascular alterations in diabetic kidney disease: A bidirectional Mendelian randomization study","authors":"Shulei Man ,&nbsp;Kefan Mou ,&nbsp;Yifan Zhang ,&nbsp;Yuzhu Gao ,&nbsp;Xue Wu ,&nbsp;Hanyue Xu ,&nbsp;Ming Zhang","doi":"10.1016/j.mvr.2026.104928","DOIUrl":"10.1016/j.mvr.2026.104928","url":null,"abstract":"<div><h3>Purpose</h3><div>Growing evidence indicates retinal thickness and microvascular changes have been associated with diabetic kidney disease (DKD). Nevertheless, the causal links between them have yet to be fully elucidated. We utilized Mendelian randomization (MR) to investigate the bidirectional causal relationship between DKD and retinal structural and vascular alterations.</div></div><div><h3>Methods</h3><div>The bidirectional two-sample MR was conducted using genome-wide association studies (GWAS) summary statistics from European populations. Eight DKD-related phenotypes were investigated in relation to retinal layer thickness and microvascular traits.</div></div><div><h3>Results</h3><div>The forward MR revealed that macroalbuminuria was associated with increased inner nuclear layer (INL) thickness (OR 1.006 [95% CI 1.000–1.012], <em>P</em> = 0.040), and the combined phenotype of chronic kidney disease and diabetic kidney disease (CKD-DN) was linked to greater choroidal thickness (OR 1.005 [95% CI 1.000–1.009], <em>P</em> = 0.047). All DKD showed negative associations with retinal vascular density (RVD) (OR 0.979 [95% CI 0.965–0.993], <em>P</em> = 0.003) and retinal vascular fractal dimension (RVFD) (OR 0.980 [95% CI 0.966–0.993], <em>P</em> = 0.004). In reverse MR, increased INL thickness predicted higher risk of end-stage renal disease (ESRD) (OR 1.444 [95% CI 1.110–1.878], <em>P</em> = 0.006) and extreme chronic kidney disease (CKD) (OR 1.322 [95% CI 1.026–1.704], <em>P</em> = 0.031). Thickening of outer retinal layers was associated with CKD (OR 1.144 [95% CI 1.020–1.284], <em>P</em> = 0.021).</div></div><div><h3>Conclusions</h3><div>These findings highlight a potential bidirectional causal link between renal dysfunction and retinal neurovascular changes. Retinal imaging biomarkers may serve as noninvasive indicators of DKD risk and progression, warranting further validation.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"166 ","pages":"Article 104928"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365569","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}
引用次数: 0
BEADS: An interactive semi-automated workflow for 3D fibrin angiogenesis assays enabling co-culture and directionality analysis 珠子:用于三维纤维蛋白血管生成分析的交互式半自动工作流程,支持共培养和方向性分析。
IF 2.7 4区 医学
Microvascular research Pub Date : 2026-05-01 Epub Date: 2026-02-03 DOI: 10.1016/j.mvr.2026.104915
Cailin R. Gonyea , Brielle Hayward-Piatkovskyi , Jason P. Gleghorn
{"title":"BEADS: An interactive semi-automated workflow for 3D fibrin angiogenesis assays enabling co-culture and directionality analysis","authors":"Cailin R. Gonyea ,&nbsp;Brielle Hayward-Piatkovskyi ,&nbsp;Jason P. Gleghorn","doi":"10.1016/j.mvr.2026.104915","DOIUrl":"10.1016/j.mvr.2026.104915","url":null,"abstract":"<div><div>3D fibrin bead angiogenesis assays are widely used to study endothelial sprouting <em>in vitro</em>, yet current analytical approaches are either time-consuming or poorly adaptable to complex imaging conditions, limiting quantitative assessment of co-cultures, spatial interactions, and nearest-neighbor-dependent angiogenic behavior. In this study, we developed a semi-automated user-interactive image analysis pipeline, Bead-based Endothelial Angiogenesis Data Suite (BEADS), to provide standardized quantitative bead-centric metrics of sprouting, migration, and spatial orientation in 3D fibrin angiogenesis assays. BEADS integrates automated bead detection with manual correction, followed by guided sprout and migratory-cell annotation across multi-channel image z-stacks. Novel analytical capabilities include co-culture designation, nearest-neighbor pairing, and circular statistics for sprout-directionality quantification. Performance was evaluated in assays using co-cultured male and female human pulmonary microvascular endothelial cell (HPMEC)-coated beads. BEADS reduced hands-on analysis time approximately sevenfold compared with manual tracing while preserving sprout-length accuracy against manual ground truth. BEADS provides a standardized, extensible platform for microvascular image analysis, supporting co-culture experimentation, spatial endothelial-interaction metrics, migratory-cell quantification, and high-throughput adaptation. This semi-automated workflow enables quantitative microvascular research by integrating computational precision with endothelial behavior and is broadly applicable to angiogenesis assays that incorporate co-cultures, perturbations, or multi-label experimental designs.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"165 ","pages":"Article 104915"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125486","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}
引用次数: 0
Dose-dependent effects of diamide and glutaraldehyde on red blood cell deformability, viscosity, and morphology 二胺和戊二醛对红细胞变形、黏度和形态的剂量依赖性影响。
IF 2.7 4区 医学
Microvascular research Pub Date : 2026-05-01 Epub Date: 2026-02-04 DOI: 10.1016/j.mvr.2026.104917
Tatiana Turcitu, Kyle Champagne, Andy Vinh Le, Marianne Fenech
{"title":"Dose-dependent effects of diamide and glutaraldehyde on red blood cell deformability, viscosity, and morphology","authors":"Tatiana Turcitu,&nbsp;Kyle Champagne,&nbsp;Andy Vinh Le,&nbsp;Marianne Fenech","doi":"10.1016/j.mvr.2026.104917","DOIUrl":"10.1016/j.mvr.2026.104917","url":null,"abstract":"<div><div>Red blood cells (RBC) deformability enables passage through capillaries, ensuring efficient microcirculatory flow and oxygen transport. Impaired deformability contributes to vascular complications and is associated with conditions such as sickle cell anemia, hereditary spherocytosis, and diabetes. Diamide and glutaraldehyde are commonly used in vitro to simulate pathological rigidity, yet their dose-dependent effects on RBC mechanics remain incompletely characterized.</div><div>This study investigates the effects of diamide (10–200 μM) and glutaraldehyde (8–159,800 μM) on RBC morphology, deformability and viscosity at 20% hematocrit (HCT). Deformability was assessed by ektacytometry, viscosity by microfluidic viscometry, and morphology by defocusing microscopy with sphericity analysis. Osmolality and HCT were also measured to link the mechanical changes observed. Diamide produced a biphasic response: the maximum elongation index (EIₘₐₓ) decreased up to 140 μM, then partially recovered at higher concentrations. This coincided with increased sphericity, reduced cell volume and surface area, decreased HCT from hemolysis, and a non-monotonous viscosity profile. These effects reflect the combined influence of oxidative stress, vesiculation, and altered cell geometry. In contrast, glutaraldehyde induced an abrupt and irreversible loss of deformability at ≥7990 μM, while morphology and osmolality remained stable. HCT values were consistently lower across concentrations, which we attribute to reduced microtube filling efficiency by rigidified cells. Despite near-zero EIₘₐₓ at high concentrations, viscosity changes were modest due to extreme rigidification.</div><div>These findings show that viscosity is governed not only by deformability but also by morphology, hemolysis and suspension dynamics.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"165 ","pages":"Article 104917"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132203","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}
引用次数: 0
Practical method for endothelial glycocalyx imaging in formalin-fixed, paraffin-embedded tissues in vascular pathology 血管病理中福尔马林固定石蜡包埋组织内皮糖萼成像的实用方法。
IF 2.7 4区 医学
Microvascular research Pub Date : 2026-05-01 Epub Date: 2026-01-23 DOI: 10.1016/j.mvr.2026.104913
Kosuke Mori , Hiroyuki Tomita , Masashi Kuno , Tomohiro Iida , Yoshihiko Yamakita , Chihiro Takada , Aika Kuriyama , Shinsuke Nakamura , Masamitsu Shimazawa , Toshiaki Hirose , Mayu Sakakibara , Hidetaka Suga , Shigeyuki Sugie , Hideshi Okada , Akira Hara
{"title":"Practical method for endothelial glycocalyx imaging in formalin-fixed, paraffin-embedded tissues in vascular pathology","authors":"Kosuke Mori ,&nbsp;Hiroyuki Tomita ,&nbsp;Masashi Kuno ,&nbsp;Tomohiro Iida ,&nbsp;Yoshihiko Yamakita ,&nbsp;Chihiro Takada ,&nbsp;Aika Kuriyama ,&nbsp;Shinsuke Nakamura ,&nbsp;Masamitsu Shimazawa ,&nbsp;Toshiaki Hirose ,&nbsp;Mayu Sakakibara ,&nbsp;Hidetaka Suga ,&nbsp;Shigeyuki Sugie ,&nbsp;Hideshi Okada ,&nbsp;Akira Hara","doi":"10.1016/j.mvr.2026.104913","DOIUrl":"10.1016/j.mvr.2026.104913","url":null,"abstract":"<div><div>The endothelial glycocalyx (eGCX), a delicate carbohydrate-rich layer coating the vascular endothelium, critically regulates vascular homeostasis, controlling permeability, thrombosis, and inflammation. Despite its fundamental importance, assessing the morphology of the eGCX remains technically challenging because of its fragile structure, which collapses during conventional fixation. Existing visualization methods require complex preparation, expensive equipment, and fresh tissues, severely limiting accessibility and clinical applicability. Here, we present a practical approach for visualizing and semi-quantitatively phenotyping the eGCX using formalin-fixed, paraffin-embedded (FFPE) tissue sections prepared via specialized Alcian blue fixation, followed by strategic integration of silver enhancement staining and low-vacuum scanning electron microscopy. The proposed method enabled robust visualization of eGCX across multiple vascular beds, including brain parenchymal vessels, choroid plexus fenestrated capillaries, and retinal vasculature, along with a thickness-based index suitable for between-condition comparisons among FFPE sections. The technique demonstrated high sensitivity in detecting pathological alterations, evidenced by near-complete eGCX loss in retinal vein occlusion models with significant reductions in thickness and lectin fluorescence intensity. Finally, the workflow was successfully applied to human colorectal surgical specimens processed via immediate Alcian blue immersion fixation, enabling visualization of vascular eGCX in FFPE clinical sections. Overall, these findings support an accessible FFPE-compatible approach for wide-field eGCX imaging and pathology-oriented phenotyping.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"165 ","pages":"Article 104913"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046391","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}
引用次数: 0
Distribution and microstructure of the endothelial glycocalyx in the blood-brain barrier 血脑屏障内皮糖萼的分布和微结构。
IF 2.7 4区 医学
Microvascular research Pub Date : 2026-05-01 Epub Date: 2026-01-14 DOI: 10.1016/j.mvr.2026.104903
Kyunghwun Chung , Jae Gyeong Kim , Chungyoul Choe , Seongtae Jeong
{"title":"Distribution and microstructure of the endothelial glycocalyx in the blood-brain barrier","authors":"Kyunghwun Chung ,&nbsp;Jae Gyeong Kim ,&nbsp;Chungyoul Choe ,&nbsp;Seongtae Jeong","doi":"10.1016/j.mvr.2026.104903","DOIUrl":"10.1016/j.mvr.2026.104903","url":null,"abstract":"","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"165 ","pages":"Article 104903"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989831","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}
引用次数: 0
A visualization of inhibitory effects on VEGF-mediated signaling pathway in proliferating endothelial cells in neonatal mouse retina 新生小鼠视网膜内皮细胞增殖过程中vegf介导的信号通路抑制作用的可视化研究。
IF 2.7 4区 医学
Microvascular research Pub Date : 2026-05-01 Epub Date: 2026-01-26 DOI: 10.1016/j.mvr.2026.104911
Akane Morita, Kasumi Miyanaga, Tsutomu Nakahara
{"title":"A visualization of inhibitory effects on VEGF-mediated signaling pathway in proliferating endothelial cells in neonatal mouse retina","authors":"Akane Morita,&nbsp;Kasumi Miyanaga,&nbsp;Tsutomu Nakahara","doi":"10.1016/j.mvr.2026.104911","DOIUrl":"10.1016/j.mvr.2026.104911","url":null,"abstract":"<div><div>Vascular endothelial growth factor (VEGF) promotes physiological and pathological retinal angiogenesis by activating the mammalian target of rapamycin complex 1 (mTORC1) pathway in proliferating endothelial cells. This study aimed to visualize the status of the VEGF receptor (VEGFR) pathway in endothelial cells by assessing the phosphorylation of S6 protein (pS6), a downstream marker of mTORC1 activity, in the neonatal mouse retina. Four-day-old mice received subcutaneous injections of rapamycin (mTORC1 inhibitor), PF-4708671 (S6 kinase 1 inhibitor), KRN633 (VEGFR tyrosine kinase inhibitor), or vehicle. The eyes were collected 1, 3, 6, 24, and 48 h after treatment. The vascular density, pS6 distribution, and proliferative activity were evaluated in the retina. pS6 immunoreactivity was detected in developing blood vessels, astrocytes, and microglial cells. Both rapamycin and PF-4708671 almost completely abolished pS6 immunoreactivity in vascular and non-vascular cells 6 h after treatment and thereafter suppressed endothelial cell proliferation before the onset of capillary degeneration. In contrast, KRN633 markedly reduced pS6 immunoreactivity associated with endothelial cells, but not in non-vascular cells at 6 h post-treatment; however, capillary endothelial cell degeneration became apparent at 24 h. These results suggest that VEGFR inhibition disrupts the mTORC1 pathway in endothelial cells within 6 h of treatment, causing endothelial cell degeneration or death in developing retinal blood vessels. Monitoring changes in pS6 immunoreactivity before the onset of endothelial cell degeneration may serve as a valuable method for assessing endothelial responses to VEGF in the retina.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"165 ","pages":"Article 104911"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146064927","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}
引用次数: 0
Tumor-induced radial vascular patterning in the chick chorioallantoic membrane 肿瘤诱导的鸡绒毛膜尿囊膜径向血管模式。
IF 2.7 4区 医学
Microvascular research Pub Date : 2026-05-01 Epub Date: 2026-01-29 DOI: 10.1016/j.mvr.2026.104914
Kenji Chamoto , Jennifer M. Pan , Jae M. Cho , Hassan A. Khalil , Maximilian Ackermann , Steven J. Mentzer
{"title":"Tumor-induced radial vascular patterning in the chick chorioallantoic membrane","authors":"Kenji Chamoto ,&nbsp;Jennifer M. Pan ,&nbsp;Jae M. Cho ,&nbsp;Hassan A. Khalil ,&nbsp;Maximilian Ackermann ,&nbsp;Steven J. Mentzer","doi":"10.1016/j.mvr.2026.104914","DOIUrl":"10.1016/j.mvr.2026.104914","url":null,"abstract":"<div><div>Tumor implantation on the chick chorioallantoic membrane (CAM) produces a characteristic radial or “starburst” microvascular pattern, classically attributed to tumor angiogenesis factor–driven sprouting. Here, we investigated the structural and functional basis of this pattern using intravital fluorescence microscopy, particle tracking, corrosion casting, scanning electron microscopy, and transcriptional profiling across 13 tumor cell lines. Eight cell lines successfully engrafted; six formed localized tumor masses associated with a rapid, well-defined radial vascular pattern evident within three days, while two exhibited diffuse, infiltrative growth with generalized capillary hypertrophy. Functional imaging revealed preferential flow paths, capillary loops, and U-turn particle trajectories at tumor margins. Structural analysis demonstrated that radial vessels arose predominantly from intussusceptive angiogenesis, with vessel duplication and intraluminal pillar formation, rather than endothelial proliferation alone. In contrast, diffuse tumors lacked radial organization despite robust capillary hypertrophy. Bulk transcriptional profiling failed to identify a distinctive angiogenic gene signature. These findings demonstrate that intussusceptive duplication underlies tumor-induced radial vascular patterning in the CAM.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"165 ","pages":"Article 104914"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097242","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}
引用次数: 0
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