Microvascular research最新文献

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"title":"Associations of sleep duration and nocturnal oxygenation with OCT-derived retinal arterial structure","authors":"Ran Xiang ,&nbsp;Yuki Muraoka ,&nbsp;Kimihiko Murase ,&nbsp;Takahiro Kogo ,&nbsp;Susumu Sato ,&nbsp;Yu Hidaka ,&nbsp;Masahiro Akada ,&nbsp;Yuki Mori ,&nbsp;Masayuki Hata ,&nbsp;Masahiro Miyake ,&nbsp;Tadao Nagasaki ,&nbsp;Takeshi Matsumoto ,&nbsp;Hironobu Sunadome ,&nbsp;Satoshi Hamada ,&nbsp;Naomi Takahashi ,&nbsp;Tomoko Wakamura ,&nbsp;Naoko Komenami ,&nbsp;Yasuharu Tabara ,&nbsp;Satoshi Morita ,&nbsp;Toyohiro Hirai ,&nbsp;Akitaka Tsujikawa","doi":"10.1016/j.mvr.2026.104912","DOIUrl":"10.1016/j.mvr.2026.104912","url":null,"abstract":"<div><h3>Purpose</h3><div>To examine the associations of objectively measured sleep parameters (sleep duration, efficiency, and nocturnal oxygen desaturation) with retinal arterial structure assessed using optical coherence tomography (OCT).</div></div><div><h3>Methods</h3><div>This cross-sectional study included 5991 adults from the community-based Nagahama Study in Japan (2012–2016). All participants underwent OCT and wrist actigraphy. Retinal arterial outer diameter (OD), inner diameter (ID), and wall thickness were measured from peripapillary OCT B-scans. Sleep period time (SPT) and sleep efficiency (defined as total sleep time divided by SPT) were derived from actigraphy. Nocturnal oxygen desaturation was evaluated using the 3% oxygen desaturation index (3%ODI) obtained from synchronized actigraphy and oximetry recordings. Associations between retinal arterial parameters and sleep/oxygenation metrics were evaluated using multivariable linear regression models adjusted for demographic, ocular, and systemic covariates.</div></div><div><h3>Results</h3><div>Among 5991 participants (mean age 57.6 years; 30.6% male), shorter sleep duration was associated with narrower retinal arterial diameters (OD: β = 0.399; 95% confidence interval [CI], 0.165–0.632; ID: β = 0.402; 95% CI, 0.188–0.616). Higher 3%ODI were associated with thicker arterial walls (β = 0.121; 95% CI, 0.050–0.192) and wider OD (β = 0.431; 95% CI, 0.003–0.859). Sleep efficiency showed no significant associations with any vascular parameter.</div></div><div><h3>Conclusions</h3><div>Sleep duration and nocturnal oxygen desaturation showed distinct associations with retinal arterial characteristics. OCT-based vascular metrics may serve as noninvasive indicators of sleep-related microvascular alterations.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"165 ","pages":"Article 104912"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037122","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":"Blood viscosity – The unifying cardiovascular disease risk biomarker","authors":"Erik Finlayson","doi":"10.1016/j.mvr.2026.104904","DOIUrl":"10.1016/j.mvr.2026.104904","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>Blood viscosity is associated with all known cardiovascular risk factors.</div></span></li><li><span>•</span><span><div>The treatment of all known cardiovascular risk factors also decreases blood viscosity.</div></span></li><li><span>•</span><span><div>The measurement of blood viscosity may help to guide the treatment of cardiovascular disease risk.</div></span></li></ul></div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"164 ","pages":"Article 104904"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998529","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}