Microcirculation最新文献

{"title":"Microcirculation From Head to Toe","authors":"Liping Zhang, Stephen T. Hammond, Julie Leonard-Duke, Galina Yu. Mironova, Reetu Singh, Sonia Taib, Nien-Wen Wu, Janaka Senarathna, Jamie E. Meegan","doi":"10.1111/micc.70037","DOIUrl":"10.1111/micc.70037","url":null,"abstract":"","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708128","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":"The Comparative Validity of the Sublabial Fossa to the Sublingual Triangle in Sidestream Dark Field Videomicroscopy for Measuring Microcirculatory Parameters","authors":"Trent Payne,&nbsp;Ryan Homes,&nbsp;Raushan Lala,&nbsp;Ruth E. Hubbard,&nbsp;Mark Midwinter","doi":"10.1111/micc.70038","DOIUrl":"10.1111/micc.70038","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study compared microcirculatory measures using sidestream dark field (SDF) videomicroscopy at sublingual and sublabial regions, examining whether novice examiners can achieve comparable reliability to experienced operators and the effect of operator experience on sublabial image quality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Microcirculatory imaging was performed using SDF videomicroscopy at the sublingual and sublabial regions. Sublingually, the probe was placed under the tongue on the mucosa of the floor of the mouth, in a stable, flat position to minimize tissue distortion. Sub-labially, the probe was positioned on the mucosa medial to the superior labial frenulum and stabilized between the central and lateral incisors. Participants were positioned at a 40-degree incline. Both novice and experienced operators captured images, and manually analyzed clips in AVA 3.2 software. All images were evaluated using the microcirculatory image quality score. Total vessel density, perfused vessel density, portion of perfused vessels, microvascular flow index, and heterogeneity index were calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No statistically significant differences in image quality scores were found between observers at the sublabial site. Vessel density measures demonstrated reliable inter-observer agreement, while some flow indices showed proportional bias (MFI, <i>p</i> = 0.01). No significant differences were detected between sublingual and sublabial regions for most measures, except for the microvascular flow index.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The sublabial site is a valid alternative to the sublingual region for measuring certain microcirculatory parameters, though it requires further evaluation in flow metrics.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678128","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":"AP-1 Is an Initial Convergent Transcriptional Response in Lymphatic Endothelium to VEGF-C or TNFα","authors":"Ewa A. Kreft,&nbsp;Zuzanna J. Juśkiewicz,&nbsp;Brant E. Isakson","doi":"10.1111/micc.70035","DOIUrl":"10.1111/micc.70035","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The lymphatic vasculature plays a central role in resolving inflammation by draining interstitial fluid, immune cells, and inflammatory mediators. While vascular endothelial growth factor C (VEGF-C) is a well-established driver of lymphangiogenesis, the effects of chronic pro-inflammatory cytokines on lymphatic remodeling remain incompletely defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we investigated how tumor necrosis factor alpha (TNFα) compares with VEGF-C in regulating lymphatic endothelial structure and function using human dermal lymphatic endothelial cells (HDLECs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In tube formation and spheroid sprouting assays, both VEGF-C and TNFα supported early lymphangiogenic events, promoting robust sprouting and network development within 24 h. However, when pre-formed microvascular networks were challenged, prolonged TNFα exposure triggered progressive destabilization, characterized by tube fragmentation, reduced proliferation, and impaired metabolic activity, whereas VEGF-C preserved network stability. Mechanistically, both VEGF-C and TNFα induced rapid phosphorylation of p38 MAPK and upregulation of Activator Protein-1 (AP-1) transcription factor subunits within 30 min, suggesting a convergent early transcriptional response. Bulk RNA-sequencing confirmed shared induction of AP-1 family genes (FOS, JUN, ATF), highlighting AP-1 as a candidate regulator of the transition between adaptive and maladaptive outcomes. We propose that transient AP-1 activation promotes pro-lymphangiogenic programs, while sustained TNFα signaling redirects AP-1 activity toward stress, growth arrest, and apoptosis, leading to lymphatic regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings identify TNFα as a temporally bifunctional regulator of lymphatic endothelial fate.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 8","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12641241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145588255","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":"Immersion-Based Clearing and Autofluorescence Quenching in Myocardial Tissue","authors":"Victoria E. Sturgess,&nbsp;Nadia K. Korovesis,&nbsp;Domingo E. Uceda,&nbsp;Ali Citalan-Madrid,&nbsp;Eric V. Vu,&nbsp;Katherine Stangis,&nbsp;Françoise Van den Bergh,&nbsp;Salman I. Essajee,&nbsp;Binyamin Jacobovitz,&nbsp;Gregory B. Sands,&nbsp;Daniel A. Lawrence,&nbsp;Johnathan D. Tune,&nbsp;Daniel A. Beard,&nbsp;Geoffrey G. Murphy,&nbsp;C. Alberto Figueroa","doi":"10.1111/micc.70034","DOIUrl":"10.1111/micc.70034","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Recent innovations in optical microscopy and tissue preparation permit 3D visualization of complex microvascular networks. Tissue clearing techniques improve light penetration and extend imaging depth. Typically, perfusion-based approaches are used for vascular labeling and tissue clearing. However, immersion-based methodologies provide enhanced practicality when processing tissues from larger animal models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We present an immersion-based microvascular labeling and tissue clearing protocol for myocardial tissues using tomato lectin and CUBIC (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational analysis), demonstrating success for imaging depths of up to 150 μm. This protocol optimized the delipidation and quenching stages for rat and pig myocardial tissues. Image quality was assessed using an automated analysis of signal-to-noise ratios (SNR) and average z-slice intensities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Optimal image quality was obtained with 24-h CUBIC Reagent I incubation times. Quenching agents TrueVIEW, Glycine, and Trypan Blue did not significantly impact SNR values. TrueBlack and Sudan Black B showed trends of reduced imaging depth compared to controls without quencher incubation. Overall, rat myocardial tissues had higher SNRs than pig tissue samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This protocol provides a rigorous foundation for the optimization of immersion-based approaches for myocardial tissue clearing. Future studies will quantify anatomical and topological coronary microvascular to compare disease states.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 8","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452272","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":"CaMKII Antagonism Improves Vascular Dysfunction in the Visceral Adipose Microvasculature of Obese Subjects","authors":"Bulbul Ahmed,&nbsp;Melissa G. Farb,&nbsp;Sophia D'Alessandro,&nbsp;Luise Pernar,&nbsp;Brain Carmine,&nbsp;Donald T. Hess,&nbsp;Kenneth Walsh,&nbsp;Noyan Gokce","doi":"10.1111/micc.70033","DOIUrl":"10.1111/micc.70033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We have previously demonstrated angiogenic impairment, inflammation, and endothelial vasomotor dysfunction in the visceral adipose vasculature of obese individuals. Here, we investigated the role of calcium/calmodulin-dependent protein kinase II (CaMKII) in the regulation of vascular phenotype in the adipose microvasculature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using visceral and subcutaneous fat specimens biopsied from obese subjects (BMI 48 ± 9 kg/m², age 38 ± 11 years), we examined the effect of CaMKII antagonism on acetylcholine-mediated, endothelium-dependent vasodilation of isolated arterioles using videomicroscopy and studied angiogenic capillary sprouting capacity ex vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Pharmacological inhibition of CaMKII with KN-93 improved endothelium-dependent vasodilation of isolated visceral arterioles by 3-fold (<i>p</i> &lt; 0.001 vs. control) and increased visceral fat sprouting capacity by 2.5-fold (<i>p</i> &lt; 0.001). Inhibition of endothelial nitric oxide synthase with N(ω)-nitro-l-arginine methyl ester blunted KN-93-induced improvements in vasodilation and angiogenesis, suggesting dependence on increased nitric oxide bioavailability. KN-93 had no effect on subcutaneous angiogenic capacity, which exhibited preserved angiogenic growth compared to visceral fat. KN-93 exposure was associated with reduced reactive oxygen species generation and decreased vascular gene expression of <i>JUN</i>, <i>NFAT5</i>, and <i>CAMKII</i> signaling components.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that CaMKII signaling may negatively modulate microvascular function, contribute to increased oxidative stress, and pro-inflammation observed in the visceral adipose microenvironment in obesity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 7","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345969","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":"Observational Study of Sublingual Microcirculation in Patients With Chronic Cardiovascular Disease","authors":"Jacob Niculcea,&nbsp;James W. Schurr,&nbsp;Fatima M. Talebi,&nbsp;Joyce W. Wald,&nbsp;John C. Greenwood","doi":"10.1111/micc.70032","DOIUrl":"10.1111/micc.70032","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sublingual video microscopy is increasingly used to study the microcirculation in acute illness. However, the sublingual microcirculation in patients with chronic cardiovascular diseases (CVD) is understudied. Our objective was to quantify sublingual microcirculatory parameters in a large cohort of patients with CVD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>One hundred and thirteen patients with CVD were enrolled. Incident dark-field handheld video microscopy (IDF-HVM) was used to quantify microvascular flow index (MFI), microvascular heterogeneity index (MHI), proportion of perfused vessels (PPV), perfused vessel density (PVD), and total vessel density (TVD). Data were stratified by age quartiles (20–39, 40–59, 60–79, 80+), cardiovascular comorbidities (hypertension, diabetes, chronic kidney disease, coronary artery disease, heart failure), and systemic hemodynamics (mean arterial pressure and pulse pressure).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In our 113 patient cohort, overall MFI = 2.86 ± 0.20; MHI = 0.15 ± 0.20; PPV = 94.3% ± 4.9%; PVD = 23.1 ± 4.7 mm/mm²; and TVD = 24.5 ± 4.8 mm/mm². Diabetic patients had lower mean MHI (0.10 vs. 0.17; <i>p</i> = 0.046) compared to those without diabetes. There was no difference in sublingual parameters attributable to other CVDs, age, or hemodynamics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In patients with stable cardiovascular disease, sublingual microvascular parameters are similar across age, blood pressure, and comorbidity cohorts, with the exception of decreased MHI in diabetic patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 7","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12517397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280529","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":"Effects of Different Isometric Exercise Modalities on Microvascular and Metabolic Function","authors":"Minyoung Kwak,&nbsp;Brian Benitez,&nbsp;Clara J. Mitchinson,&nbsp;Erik R. Snell,&nbsp;Haley C. Bergstrom","doi":"10.1111/micc.70031","DOIUrl":"10.1111/micc.70031","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study compared near-infrared spectroscopy (NIRS)-derived microvascular function, muscle oxygenation (SmO₂) dynamics, and fatigability during sustained isometric forearm flexion under two conditions: a rating of perceived exertion (RPE) level of 3 (RPE-Clamp) versus a constant torque (CT) matched to the torque produced during the first second of RPE-Clamp.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirteen healthy males (22.2 ± 4.7 year) completed both tasks on separate days. SmO₂ was measured during exercise, maximal voluntary isometric contractions (MVIC) were performed before and after exercise, and time to task failure (TTF) was recorded. Vascular occlusion tests (VOT) were used to assess microvascular function pre- and post-exercise.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CT induced significantly greater performance fatigability than RPE-Clamp (<i>p</i> &lt; 0.001), despite similar TTF (<i>p</i> = 0.171). SmO₂ significantly decreased during early (<i>p</i> = 0.001) and final (<i>p</i> = 0.028) phases of CT, while increasing during mid (<i>p</i> &lt; 0.001) phases in RPE-Clamp. Post-VOT indicated a significantly reduced desaturation rate (slope 1; <i>p</i> &lt; 0.001), a greater extent of tissue hypoxia (minimum SmO₂; <i>p</i> = 0.003), and increased microvascular reactivity (slope 2; <i>p</i> = 0.021) than pre-VOT, with greater peak re-saturation (MaxSmO₂; <i>p</i> = 0.010) observed in CT than RPE-Clamp.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Despite greater fatigability and desaturation in CT, both exercise modalities may enhance microvascular reactivity. Prolonged isometric exercise and subsequent hypoxic stress may contribute to a reduced desaturation rate post-exercise.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 7","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280618","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":"Apolipoprotein M (ApoM) Ameliorates Acute Alcohol Intoxication (AAI)-Hemorrhagic Shock and Resuscitation (HSR)-Induced Microvascular Leakage","authors":"Mengmeng Chang,&nbsp;Jerome W. Breslin","doi":"10.1111/micc.70030","DOIUrl":"https://doi.org/10.1111/micc.70030","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Microvascular hyperpermeability is a serious complication that occurs from hemorrhagic shock and resuscitation (HSR), especially when combined with acute alcohol intoxication (AAI). We tested the hypothesis that administration of Apolipoprotein M (ApoM), a lipocalin that normally resides in plasma high-density lipoproteins (HDL) and a carrier of sphingosine-1-phosphate (S1P), reduces combined AAI and HSR-induced microvascular leakage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An established rat model of AAI/HSR was combined with intravital microscopy to study whether the administration of ApoM in resuscitative fluids reduces microvascular leakage of FITC-albumin. The impact of ApoM on human umbilical vein endothelial cell (HUVEC) monolayer barrier function and junctional integrity was tested, using trans-endothelial electrical resistance (TER) and immunofluorescence labeling of junctional VE-Cadherin, respectively. Immunoprecipitation of ApoM in HUVEC and mass spectrometry of complexes were used to determine potential binding partners. The Rac1 G-LISA assay was used to determine if ApoM causes Rac1 activation in HUVEC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to sham controls, combined AAI and HSR significantly increased microvascular leakage. Administration of S1P, ApoM, or their combination during resuscitation significantly decreased microvascular leakage. In HUVEC monolayers, with or without alcohol pretreatment, S1P, ApoM, and S1P + ApoM all significantly increased barrier function and improved the junctional integrity of VE-cadherin compromised by alcohol. The small GTPase Rac1 was found to bind with ApoM in HUVEC and was significantly activated within 5 min of ApoM addition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The findings suggest that fluid resuscitation with ApoM ameliorates AAI/HSR-induced microvascular leakage. The mechanism involves stabilizing VE-Cadherin junction integrity, which could be caused by Rac1 activation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 7","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.70030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145272455","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":"Shear Stress Regulates ABCA1-Dependent Membrane Cholesterol Content in Endothelial Cells Facilitating H2S-Dependent Vasodilation","authors":"Jacob R. Anderson,&nbsp;Nancy L. Kanagy,&nbsp;Laura V. Gonzalez Bosc,&nbsp;Jay S. Naik","doi":"10.1111/micc.70029","DOIUrl":"10.1111/micc.70029","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Endothelial cells (ECs) express an array of integral membrane proteins, including ion channels and transporters that contribute to blood flow regulation and cell–cell communication. Many of these membrane proteins are regulated by plasma membrane cholesterol content. The ATP-binding cassette family A1 (ABCA1) transporter is a regulator of membrane cholesterol content. We have shown increased ABCA1 mRNA expression and reduced EC membrane cholesterol in resistance mesenteric arteries compared to conduit arteries. Previous studies suggest shear stress (SS) can increase or decrease ABCA1 expression in a cell-type-dependent manner.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Hypothesis</h3>\u0000 \u0000 <p>SS sustains lower EC membrane cholesterol concentration through ABCA1-mediated cholesterol transport, facilitating H₂S-mediated vasodilation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The effect of SS on ABCA1 and membrane cholesterol content was assessed in pressurized mesenteric arteries from male Sprague–Dawley rats and cultured human aortic endothelial cells. Pressure myography was used to assess the effects of ABCA1 inhibition on H₂S-mediated vasodilation. Filipin was used to assess EC membrane cholesterol content.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SS increased ABCA1 expression in the endothelium of mesenteric arteries and cultured human aortic endothelial cells and markedly reduced EC membrane cholesterol. Inhibition of ABCA1 increased EC membrane cholesterol content and abolished H₂S-induced vasodilation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SS facilitation of EC-dependent vasodilation appears to be mediated by membrane cholesterol content.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 7","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12498007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232828","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":"Volumetric Analysis of the Blood–Brain Barrier After Ischemic Stroke by Electron Tomography in Mice","authors":"Pavel Kotchetkov,&nbsp;Baptiste Lacoste","doi":"10.1111/micc.70025","DOIUrl":"https://doi.org/10.1111/micc.70025","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Transmission electron microscopy (TEM) enables ultrastructural investigation of both organic and nonorganic samples. However, conventional TEM is limited by the acquisition of two-dimensional snapshots, restricting our volumetric understanding of complex ultrastructures. Electron tomography (ET) overcomes this limitation by offering detailed three-dimensional (3D) specimen representation. ET has been widely applied in biology; however, its use for blood–brain barrier (BBB) assessment has been overlooked. The BBB ensures proper brain function by limiting the entrance of blood-borne molecules into the brain and ensuring selective transport. The BBB is disrupted in several pathological conditions, resulting in neuronal damage. Understanding the fine changes underlying BBB disruption requires advanced imaging tools such as ET.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We developed a detailed room temperature electron tomography (RT-ET) method for sample preparation, tomogram generation, 3D segmentation, and applied this approach to assess ultrastructural changes in brain endothelial cells (ECs) after photothrombotic stroke in mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings identify altered transcytotic vesicle morphology, as well as remodeling of the endoplasmic reticulum, indicative of cellular stress and impaired vesicular trafficking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our toolkit allows for reproducible, high-resolution analysis of brain microvascular pathology. This new RT-ET approach uncovers previously inaccessible ultrastructural alterations in ECs following ischemic stroke in mice, offering new insight into mechanisms of BBB disruption.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 7","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102296","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}