Jinfeng Cui , Liqing Luo , Hongmei Geng , Yunxiu Gao , Yuanyuan Chen , Qilin Yu , Xiao Huang , Xiaozhi Wang , Ting Sun
{"title":"Proteomics suggests the role of Cxcl12 secreted by hucMSCs in the treatment of lipopolysaccharide-acute lung injury","authors":"Jinfeng Cui , Liqing Luo , Hongmei Geng , Yunxiu Gao , Yuanyuan Chen , Qilin Yu , Xiao Huang , Xiaozhi Wang , Ting Sun","doi":"10.1016/j.mvr.2025.104815","DOIUrl":"10.1016/j.mvr.2025.104815","url":null,"abstract":"<div><div>Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by a high mortality rate, and its treatment is relatively straightforward. The application of human umbilical cord mesenchymal stem cells (hucMSCs) for the treatment of ARDS has emerged as a novel therapeutic approach and has been the subject of extensive research. In this study, a mouse model of acute lung injury (ALI) was established, and hucMSCs were administered via tail vein injection to investigate the pathogenesis of ARDS and the protein alterations following hucMSC treatment. Data-independent acquisition (DIA) was employed for the proteomic analysis of lung tissue, which included the identification of differentially expressed proteins (DEPs) and their associated pathways. The relevant DEPs identified in the lung tissues of the three groups of mice included Arid5a, Mrpl4, Cxcl12, and Rnf121 (<em>P</em> <0.05). Silencing the expression of Cxcl12 in hucMSCs could significantly inhibit the therapeutic effect of hucMSCs in reducing the permeability of lung tissue and endothelial cells (<em>P</em> < 0.05). Additionally, the signaling pathways associated with the relevant DEPs were analyzed. The DEPs and the enriched pathways discussed herein provide valuable insights into the pathogenesis of ARDS and the potential applications of hucMSCs.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104815"},"PeriodicalIF":2.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898991","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":"Effects of veno-arterial extracorporeal membrane oxygenation on skeletal muscle function and interstitial PO2 in contracting muscle of normal rats","authors":"Kazuki Hotta , Yutaka Fujii , Naoki Hitosugi , Ren Takamizawa , Tatsuro Inoue , Hajime Tamiya , Atsuhiro Tsubaki","doi":"10.1016/j.mvr.2025.104813","DOIUrl":"10.1016/j.mvr.2025.104813","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to clarify the effects of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) on skeletal muscle oxygen pressure and function in rats.</div></div><div><h3>Methods</h3><div>Male Sprague-Dawley rats (2–3 months old, <em>n</em> = 17) were randomized into control and VA-ECMO groups. All animals were anesthetized and mechanically ventilated. The VA-ECMO circuit was established by cannulating the right jugular vein and left carotid artery. Interstitial PO<sub>2</sub> in the tibialis anterior (TA) muscle was measured using a phosphorescence quenching technique during electrically induced muscle contractions. Muscle tension was analyzed to evaluate the rate of force development (RFD) and relaxation rate.</div></div><div><h3>Results</h3><div>Compared to controls, arterial oxygen pressure (PaO<sub>2</sub>) was significantly higher, while hemoglobin levels were significantly lower in the VA-ECMO group (both <em>p</em> < 0.01). Interstitial PO<sub>2</sub> was significantly reduced at rest and during contractions in the VA-ECMO group (both <em>p</em> < 0.01). Muscle relaxation was delayed, and peak tension was lower in the VA-ECMO group compared to controls (both p < 0.01).</div></div><div><h3>Conclusions</h3><div>VA-ECMO impairs skeletal muscle function and reduces interstitial PO2 in contracting muscles, effects that appear independent of hyperoxemia. These findings provide insight into the microcirculatory and functional consequences of VA-ECMO on skeletal muscle.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104813"},"PeriodicalIF":2.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875032","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}
Khiany Mathias , Richard Simon Machado , Taise Petronilho , Victor Augusto Rodrigues Sulzbacher , Victoria Linden de Rezende , Josiane Somariva Prophiro , Fabricia Petronilho
{"title":"Glial and blood-brain barrier cell-derived exosomes: Implications in stroke","authors":"Khiany Mathias , Richard Simon Machado , Taise Petronilho , Victor Augusto Rodrigues Sulzbacher , Victoria Linden de Rezende , Josiane Somariva Prophiro , Fabricia Petronilho","doi":"10.1016/j.mvr.2025.104812","DOIUrl":"10.1016/j.mvr.2025.104812","url":null,"abstract":"<div><div>Exosomes are small extracellular vesicles released by cells that play a pivotal role in intercellular communication, significantly influencing both the pathophysiology and potential treatment of ischemic stroke (IS). This review examines exosomes derived from key brain cell types, including microglia, astrocytes, oligodendrocytes, oligodendrocyte precursor cells (NG2+ cells), endothelial cells, and pericytes, emphasizing their molecular cargo and functional impact in IS. Microglia-derived exosomes regulate neuroinflammation, with M2-type exosomes exhibiting neuroprotective effects, while astrocyte-derived exosomes modulate pathways involved in pyroptosis and autophagy, influencing neuronal survival. Oligodendrocyte and NG2+ cell-derived exosomes contribute to remyelination, axonal growth, and inflammatory modulation. Endothelial and pericyte-derived exosomes play critical roles in BBB integrity, neurovascular remodeling, and drug transport across the BBB. This synthesis highlights recent advances in understanding how exosome-mediated communication impacts IS recovery and explores their translational potential for biomarker development and targeted therapies. By manipulating exosomal composition and delivery mechanisms, novel therapeutic strategies may emerge, offering hope for improved IS treatment outcomes.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104812"},"PeriodicalIF":2.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844264","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}
Chloe French , Dan Robbins , Marie Gernigon , Dan Gordon
{"title":"The influence of cuff location on the oxygenation and reperfusion of the foot during ischemic preconditioning: A reliability study","authors":"Chloe French , Dan Robbins , Marie Gernigon , Dan Gordon","doi":"10.1016/j.mvr.2025.104811","DOIUrl":"10.1016/j.mvr.2025.104811","url":null,"abstract":"<div><div>Ischemic preconditioning (IPC) involves the application of occlusion cycles, typically prior to exercise. IPC is commonly applied at the arm or thigh for improving exercise performance, which can be combined with near-infrared spectroscopy (NIRS) to assess the microcirculation and tissue oxygenation. Despite the use of NIRS during IPC, few studies have investigated the reliability of NIRS during lower limb IPC with no relevant publications investigating IPC at the ankle. Therefore, the purpose of this study was to investigate the intra-session reliability in the NIRS measurements during repeated IPC at the thigh, ankle and arm. Eighteen participants volunteered. IPC was applied at the thigh (220 mmHg), ankle (individualized arterial occlusion pressure: 212 ± 24 mmHg) and arm (220 mmHg) in a randomized order involving 3 repeated cycles of 5-min occlusion and reperfusion, within a session. NIRS recorded tissue oxygen saturation (SO<sub>2</sub>), oxygenated (O<sub>2</sub>Hb) and deoxygenated hemoglobin (HHb) at the abductor hallucis muscle. Reliability was assessed using intraclass correlation coefficients. For all NIRS measurements assessed, there was excellent reliability (All ICC > 0.94) for the average, minimum and maximum values. The results indicate that IPC can successfully be applied at the ankle, offering reliable measures between three repeated occlusions within a session.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104811"},"PeriodicalIF":2.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839499","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":"Localized pulmonary vascular changes in a mouse model of subarachnoid hemorrhage created by combining filament perforation and blood injection","authors":"Ryota Tochinai , Takaya Suzuki , Kenji Tomita , Shin-ichi Sekizawa , Yoshinori Okada , Yasuyuki Taki , Masayoshi Kuwahara , Tatsushi Mutoh","doi":"10.1016/j.mvr.2025.104810","DOIUrl":"10.1016/j.mvr.2025.104810","url":null,"abstract":"<div><h3>Introduction</h3><div>Subarachnoid hemorrhage (SAH) results in neurogenic pulmonary edema (NPE), a condition with a high mortality rate arising from increased hydrostatic pressure and vascular permeability. Two possible mechanisms of NPE are increased hydrostatic pressure and increased vascular permeability, and it is possible that increased permeability of capillaries in the lungs may contribute to the exacerbation of NPE. Recent research has highlighted the importance of the glycocalyx, a gel-like layer that lines blood vessels, in regulating vascular permeability in various diseases. However, its role in NPE after SAH has not been previously explored. This study investigated the involvement of the glycocalyx in the development of NPE by developing a mouse model of SAH.</div></div><div><h3>Methods</h3><div>The SAH model was developed by combining internal carotid artery (ICA) perforation and blood infusion into the cisterna magna of mice. The histological structure of the lungs was confirmed using micro-CT, histopathological examination, and scanning electron microscopy.</div></div><div><h3>Results</h3><div>Despite no obvious micro-CT findings indicating pulmonary edema, histopathological changes in hematoxylin and eosin-stained lung were detected. Scanning electron microscopy revealed glycocalyx exfoliation within the pulmonary microvascular wall. A trend toward higher plasma syndecan-1 levels was also observed.</div></div><div><h3>Conclusion</h3><div>The combination of ICA perforation and blood infusion into the cisterna magna can produce pulmonary findings in mice that mimic NPE after SAH. The results also suggest that glycocalyx loss is involved in the development of NPE after SAH.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104810"},"PeriodicalIF":2.9,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839498","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":"Increase in endothelial microparticles is negatively correlated with decrease in renal microperfusion in septic rats","authors":"Xinjie Guo , Jingfeng Liu , Meili Duan","doi":"10.1016/j.mvr.2025.104809","DOIUrl":"10.1016/j.mvr.2025.104809","url":null,"abstract":"<div><h3>Introduction</h3><div>Endothelial dysfunction is an important pathophysiological mechanism of septic acute kidney injury, and endothelial microparticles (EMPs) can directly reflect the endothelial damage. However, the relationship between EMPs and renal microperfusion remains unclear. In this study, contrast-enhanced ultrasound (CEUS) imaging and side-stream dark field imaging were used to evaluate the renal microcirculatory perfusion in septic rats.</div></div><div><h3>Methods</h3><div>A cecal ligation and puncture model was established for inducing septic kidney injury in Sprague-Dawley rats. Later, the changes in mean arterial pressure (MAP), lactate level, renal artery blood flow (RBF) and mean renal artery velocity were measured. Flow cytometry was conducted to measure EMPs, CEUS imaging was performed to evaluate cortical and medullary perfusion enhancement, and side-stream dark-field imaging was carried out to detect the perfused small vessel density (PVD) and microvascular flow index of the renal cortex.</div></div><div><h3>Results</h3><div>In the sepsis group, EMPs and lactate levels increased at 12 h, macrohemodynamics (MAP and RBF) did not change, and the mean artery velocity (547.76 ± 28.40 mm/s) increased compared with the sham group (421.78 ± 34.58 mm/s). Meanwhile, cortical peak echointensity (PE), medullary PE, PVD, and microvascular flow index (MFI) decreased at 12 h. The decreases in pulsatility index (PI) and resistance index (RI) suggested the damage of vascular appearance. The pathological results revealed erythrocyte stasis in the capillaries. At 24 h, macrodynamics decreased compared with that at 12 h. The EMPs and lactate levels reached a peak at 24 h. Glomerular vascular endothelium was locally thickened. Moreover, EMPs were negatively correlated with the decreased renal microcirculatory perfusion.</div></div><div><h3>Conclusions</h3><div>This study shows that endothelial microparticles (EMPs) are closely associated with renal microcirculatory dysfunction in septic acute kidney injury (S-AKI). CEUS can sensitively reflect changes in renal microperfusion, providing earlier indications of kidney injury compared to macrocirculatory changes, and holds potential for early diagnosis of S-AKI.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104809"},"PeriodicalIF":2.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788690","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}
Kiana M. Schulze , Daniel M. Hirai , Trenton D. Colburn , Jesse C. Craig , Timothy I. Musch , David C. Poole
{"title":"KATP channel inhibition-induced hyporemia in skeletal muscle: No evidence for pre-capillary sphincter action","authors":"Kiana M. Schulze , Daniel M. Hirai , Trenton D. Colburn , Jesse C. Craig , Timothy I. Musch , David C. Poole","doi":"10.1016/j.mvr.2025.104808","DOIUrl":"10.1016/j.mvr.2025.104808","url":null,"abstract":"<div><h3>Introduction</h3><div>Whether pre-capillary sphincters are present and regulate red blood cell (RBC) flux at the individual capillary level, especially in skeletal muscle, is controversial. Recently, blockade of K<sub>ATP</sub> channels using the sulphonylurea glibenclamide (GLI) was demonstrated to reduce muscle blood flow and lower vascular conductance. The present investigation tested the hypothesis that, if pre-capillary sphincters were involved in GLI-induced blood flow reductions, a defined luminal narrowing would be evident in the proximate region of the capillaries.</div></div><div><h3>Methods</h3><div>Videomicroscopy of the spinotrapezius capillary bed was performed under control (Krebs-Henseleit) and GLI (200 μM in Krebs-Henseleit) superfusion. Capillary RBC flux was measured within individual capillaries and their luminal diameter was measured using a calibrated digital ruler at the branch-point and subsequently downstream.</div></div><div><h3>Results</h3><div>GLI reduced capillary RBC flux by 31% (<em>p</em> = 0.004). Despite the presence of a reduced RBC flux, no detectable reduction or, indeed, any change in capillary luminal diameter was present at any measurement site. The average diameter at the branching point was 4.9 ± 0.3 μm, and at 5, 10, 20 and 50 μm downstream, the average diameters were 4.8 ± 0.4, 4.8 ± 0.5, 5.0 ± 0.7, and 5.2 ± 0.4 μm, respectively and were unchanged by GLI (all <em>P</em> > 0.05).</div></div><div><h3>Conclusions</h3><div>Accordingly, the absence of any evidence for capillary luminal narrowing or constriction in these data support that the GLI-induced reductions in capillary RBC flux and muscle blood flow occur via upstream effects within the arteriolar bed. Decreases in skeletal muscle microcirculatory RBC flux with this K<sub>ATP</sub> channel blocker were not regulated by any detectable capillary structural alterations.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104808"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753485","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":"Lymphatics in the chick embryo chorioallantoic membrane","authors":"Domenico Ribatti","doi":"10.1016/j.mvr.2025.104806","DOIUrl":"10.1016/j.mvr.2025.104806","url":null,"abstract":"<div><div>The chick embryo chorioallantoic membrane (CAM) has been used as an experimental <em>in vivo</em> model to study angiogenesis and anti-angiogenesis. Moreover, due to the lack of a fully developed immunocompetent system, the CAM is suitable to study various aspects of tumor angiogenesis and metastatic potential. In this article, we emphasize the important role of the CAM also in the study of lymphangiogenesis and tumor lymphangiogenesis <em>in vivo</em>. This experimental model is more advantageous than other assays because it is a relatively simple, quick, and low-cost. Finally, it does not require administrative procedures to obtain ethics committee approval for animal experimentation.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104806"},"PeriodicalIF":2.9,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143680560","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":"Interplay between platelet and T lymphocyte after coronary artery bypass grafting (CABG): Evidence for platelet mediated post-CABG immunomodulation","authors":"Fateme Farhid , Ehteramolsadat Hosseini , Faranak Kargar , Mehran Ghasemzadeh","doi":"10.1016/j.mvr.2025.104805","DOIUrl":"10.1016/j.mvr.2025.104805","url":null,"abstract":"<div><h3>Background</h3><div>On-pump coronary artery bypass grafting (CABG) triggers inflammatory responses as a result of surgical stress and extracorporeal circulation, which affect platelet and leukocyte activation while enhancing their intimate crosstalk. Given this, the study presented here aimed to investigate platelet-T cell interaction after CABG focusing on the changes in immunomodulatory subtypes of regulatory T Cells.</div></div><div><h3>Methods</h3><div>Blood samples were obtained from twenty patients undergoing on-pump CABG at 5 different time points of 24 h before, immediately, 2 h, 24 h, and one week after surgery. Total leukocyte and lymphocyte counts were determined using an automatic cell counter. Platelet P-selectin expression, frequencies of CD4<sup>+</sup> and CD8<sup>+</sup> T cells, platelet-T cell aggregates (PTCAs), and regulatory T cells derived from CD4<sup>+</sup> (T4reg) and CD8<sup>+</sup> (T8reg) cells, were assessed by flow cytometry.</div></div><div><h3>Results</h3><div>A significant increase in total leukocyte count occurred immediately after CABG, whereas, conversely, lymphocyte and CD4<sup>+</sup> T cells but not CD8<sup>+</sup> T cells decreased 2 h after surgery. However, all these changes returned to pre-CABG baseline levels within a week. Platelet P-selectin expression increased immediately after surgery, followed by a two-hour delay after PTCA, and both returned to baseline after one week. T4regs and T8regs showed a similar increase and decrease trend, where T8regs but not T4regs returned to baseline one week after surgery.</div></div><div><h3>Conclusion</h3><div>CABG surgery induces an inflammatory response that activates platelets and enhances P-selectin expression, facilitating PTCA formation. This mechanism is critical for the dynamics and differentiation of T cells, which play an essential role in post-CABG modulation of immune responses.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104805"},"PeriodicalIF":2.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663748","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}