Microvascular research最新文献

{"title":"Digital thermography complements Laser Speckle Contrast Imaging for the diagnosis of quantified severe mesenteric traction syndrome — A prospective cohort study","authors":"August A. Olsen ,&nbsp;Stefan Burgdorf ,&nbsp;Dennis Richard Bigler ,&nbsp;Mette Siemsen ,&nbsp;Eske K. Aasvang ,&nbsp;Jens P. Goetze ,&nbsp;Morten Bo Søndergaard Svendsen ,&nbsp;Lars Bo Svendsen ,&nbsp;Michael Patrick Achiam","doi":"10.1016/j.mvr.2024.104690","DOIUrl":"https://doi.org/10.1016/j.mvr.2024.104690","url":null,"abstract":"<div><h3>Introduction</h3><p>The diagnosis of severe mesenteric traction syndrome (MTS) is based on assessing the developed degree of facial flushing. Only one validated objective diagnostic method, Laser Speckle Contrast Imaging (LSCI), exists. However, this method is sensitive to distance, motion, and angulation. Digital thermography is known to correlate well with LSCI without the same limitations, but has never been tested in relation to MTS. This study aimed to examine the thermographic changes during the development of severe MTS and to calculate a cut-off value for identifying severe MTS.</p></div><div><h3>Methods</h3><p>A prospective cohort study was performed on patients planned for open esophagectomy and pancreatic surgery from March 2021 to April 2022. All patients underwent continuous measurement on their forehead using LSCI and digital thermography during the first hour of surgery. The validated LSCI cut-off value was used to grade the severity of MTS. Blood samples and hemodynamics were collected at predefined time points.</p></div><div><h3>Results</h3><p>Fifty-seven patients were included. Patients developing severe MTS had increased facial skin temperature 15 min (<em>p</em> = 0.002) and 30 min into surgery (<em>p</em> &lt; 0.001). A cut-off value for identifying severe MTS using thermography was identified (35.55 °C, <em>p</em> &lt; 0.001). Patients identified as developing severe MTS using this cut-off value had a higher level of prostacyclin (<em>p</em> = 0.001) and lower systemic vascular resistance (<em>p</em> &lt; 0.001) 15 min into surgery, as compared with patients not developing severe MTS.</p></div><div><h3>Conclusion</h3><p>This study shows that digital thermography may complement LSCI in the objective identification of severe MTS.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"154 ","pages":"Article 104690"},"PeriodicalIF":3.1,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0026286224000396/pdfft?md5=2292610ef9de5d3ae07e00cce551254c&pid=1-s2.0-S0026286224000396-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140649322","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":"Long-term efficacy of liposomal nanocarriers of preassembled glycocalyx in restoring cerebral endothelial glycocalyx in sepsis","authors":"Shinya Ishiko ,&nbsp;An Huang ,&nbsp;Dong Sun","doi":"10.1016/j.mvr.2024.104684","DOIUrl":"10.1016/j.mvr.2024.104684","url":null,"abstract":"<div><p>The endothelial glycocalyx (EG) undergoes early degradation in sepsis. Our recent work introduced a novel therapeutic approach involving liposomal nanocarriers of preassembled glycocalyx (LNPG) to restore EG in lipopolysaccharide (LPS)-induced sepsis model of mice. While short-term effects were promising, this study focuses on the long-term impact of LNPG on mouse cerebral microcirculation. Utilizing cranial window, we assessed the stability of vascular density (VD) and perfused boundary region (PBR), an index of EG thickness, over a five-day period in normal control mice. In septic groups (LPS, LPS + 1-dose LNPG, and LPS + 2-dose LNPG), the exposure of mice to LPS significantly reduced VD and increased PBR within 3 h. Without LNPG treatment, PBR returned to the normal control level by endogenous processes at 48 h, associated with the recovery of VD to the baseline level at 72 h. However, mice receiving LNPG treatment significantly reduced the increment of PBR at 3 h. The therapeutic effect of 1-dose LNPG persisted for 6 h while the 2-dose LNPG treatment further reduced PBR and significantly increased VD at 12 h compared to LPS group. This study provides valuable insights into the potential therapeutic benefits of LNPG in mitigating EG degradation in sepsis.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"154 ","pages":"Article 104684"},"PeriodicalIF":3.1,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140781025","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":"Omentin reduces venous neointimal hyperplasia in arteriovenous fistula through hypoxia-inducible factor-1 alpha inhibition","authors":"Li Zhui,&nbsp;Chen Yuling,&nbsp;Wang Hansheng,&nbsp;Li Xiangjie","doi":"10.1016/j.mvr.2024.104688","DOIUrl":"10.1016/j.mvr.2024.104688","url":null,"abstract":"<div><p>Arteriovenous fistula (AVF) failure often involves venous neointimal hyperplasia (VNH) driven by elevated hypoxia-inducible factor-1 alpha (HIF-1α) in the venous wall. Omentin, known for its anti-inflammatory and anti-hyperplasia properties, has an uncertain role in early AVF failure. This study investigates omentin's impact on VNH using a chronic renal failure (CRF) rabbit model. The CRF rabbit model of AVF received omentin-expressing adenoviral vector or control β-gal vector to assess omentin's effects on VNH. Human vascular smooth muscle cells (HVSMCs), stimulated with tumor necrosis factor-α (TNF-α), were exposed to recombinant human omentin (Rh-OMT) to study its influence on cell proliferation and migration. The AMP-activated protein kinase (AMPK) inhibitor compound C and the mammalian target of rapamycin (mTOR) activator MHY1485 were employed to explore omentin's mechanisms in VNH reduction through HIF-1α inhibition. Omentin treatment reduced VNH in CRF rabbits, concomitant with HIF-1α down-regulation and the suppression of downstream factors, including vascular endothelial growth factor and matrix metalloproteinases. Rh-OMT inhibited TNF-α-induced HVSMC proliferation and migration by modulating both cell cycle and cell adhesion proteins. Additionally, omentin reduced HIF-1α expression through the AMPK/mTOR pathway activation. Notably, the blockade of AMPK/mTOR signaling reversed omentin-mediated inhibition of VNH, cell proliferation, and migration, both in vivo and in vitro. In conclusion, omentin mitigates VNH post-AVF creation by restraining HIF-1α via AMPK/mTOR signaling. Strategies boosting circulating omentin levels may offer promise in averting AVF failure.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"154 ","pages":"Article 104688"},"PeriodicalIF":3.1,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140788775","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 multimodal tissue perfusion measurement approach for the evaluation of the effect of pimobendan, an inodilator, in a porcine sepsis model","authors":"Mathieu Magnin ,&nbsp;Morgane Gavet ,&nbsp;Thien-Tam Ngo ,&nbsp;Vanessa Louzier ,&nbsp;Tatiana Victoni ,&nbsp;Jean Yves Ayoub ,&nbsp;Bernard Allaouchiche ,&nbsp;Jeanne-Marie Bonnet-Garin ,&nbsp;Stéphane Junot","doi":"10.1016/j.mvr.2024.104687","DOIUrl":"https://doi.org/10.1016/j.mvr.2024.104687","url":null,"abstract":"<div><p>Sepsis is associated with hypoperfusion and organ failure. The aims of the study were: 1) to assess the effect of pimobendan on macrocirculation and perfusion and 2) to describe a multimodal approach to the assessment of perfusion in sepsis and compare the evolution of the perfusion parameters.</p><p>Eighteen anaesthetized female piglets were equipped for macrocirculation monitoring. Sepsis was induced by an infusion of <em>Pseudomonas aeruginosa</em>. After the occurrence of hypotension, animals were resuscitated. Nine pigs received pimobendan at the start of resuscitation maneuvers, the others received saline. Tissue perfusion was assessed using temperature gradients measured with infrared thermography (TG = core temperature – tarsus temperature), urethral perfusion index (uPI) derived from photoplethysmography and sublingual microcirculation (Sidestream dark field imaging device): De Backer score (DBs), proportion of perfused vessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI). Arterial lactate and ScvO₂ were also measured.</p><p>Pimobendan did not improve tissue perfusion nor macrocirculation. It did not allow a reduction in the amount of noradrenaline and fluids administered. Sepsis was associated with tissue perfusion disorders: there were a significant decrease in uPI, PPV and ScvO₂ and a significant rise in TG. TG could significantly predict an increase in lactate. Resuscitation was associated with a significant increase in uPI, DBs, MFI, lactate and ScvO₂. There were fair correlations between the different perfusion parameters.</p><p>In this model, pimobendan did not show any benefit. The multimodal approach allowed the detection of tissue perfusion alteration but only temperature gradients predicted the increase in lactatemia.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"154 ","pages":"Article 104687"},"PeriodicalIF":3.1,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0026286224000360/pdfft?md5=e7bd2a03563a39cf08d48b442e6cb207&pid=1-s2.0-S0026286224000360-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140605686","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":"GBP2 inhibits pathological angiogenesis in the retina via the AKT/mTOR/VEGFA axis","authors":"Xiaoxiang Xu ,&nbsp;Xihui Ding ,&nbsp;Zizhuo Wang ,&nbsp;Shujiang Ye ,&nbsp;Jianguang Xu ,&nbsp;Zugang Liang ,&nbsp;Renfei Luo ,&nbsp;Jinyong Xu ,&nbsp;Xiaohui Li ,&nbsp;Zhenhua Ren","doi":"10.1016/j.mvr.2024.104689","DOIUrl":"10.1016/j.mvr.2024.104689","url":null,"abstract":"<div><p>Pathological retinal angiogenesis is not only the hallmark of retinopathies, but also a major cause of blindness. Guanylate binding protein 2 (GBP2) has been reported to be associated with retinal diseases such as diabetic retinopathy and hypoxic retinopathy. However, GBP2-mediated pathological retinal angiogenesis remains largely unknown. The present study aimed to investigate the role of GBP2 in pathological retinal angiogenesis and its underlying molecular mechanism. In this study, we established oxygen-induced retinopathy (OIR) mice model for in vivo study and hypoxia-induced angiogenesis in ARPE-19 cells for in vitro study. We demonstrated that GBP2 expression was markedly downregulated in the retina of mice with OIR and ARPE-19 cells treated with hypoxia, which was associated with pathological retinal angiogenesis. The regulatory mechanism of GBP2 in ARPE-19 cells was studied by GBP2 silencing and overexpression. The regulatory mechanism of GBP2 in the retina was investigated by overexpressing GBP2 in the retina of OIR mice. Mechanistically, GBP2 downregulated the expression and secretion of vascular endothelial growth factor (VEGFA) in ARPE-19 cells and retina of OIR mice. Interestingly, overexpression of GBP2 significantly inhibited neovascularization in OIR mice, conditioned medium of GBP2 overexpressing ARPE-19 cells inhibited angiogenesis in human umbilical vein endothelial cells (HUVECs). Furthermore, we confirmed that GBP2 downregulated VEGFA expression and angiogenesis by inhibiting the AKT/mTOR signaling pathway. Taken together, we concluded that GBP2 inhibited pathological retinal angiogenesis via the AKT/mTOR/VEGFA axis, thereby suggesting that GBP2 may be a therapeutic target for pathological retinal angiogenesis.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"154 ","pages":"Article 104689"},"PeriodicalIF":3.1,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140783862","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":"Pulmonary hypertension impairs vasomotor function in rat diaphragm arterioles","authors":"Kiana M. Schulze ,&nbsp;Andrew G. Horn ,&nbsp;Judy M. Muller-Delp ,&nbsp;Zachary J. White ,&nbsp;Stephanie E. Hall ,&nbsp;Steven L. Medarev ,&nbsp;Ramona E. Weber ,&nbsp;David C. Poole ,&nbsp;Timothy I. Musch ,&nbsp;Bradley J. Behnke","doi":"10.1016/j.mvr.2024.104686","DOIUrl":"10.1016/j.mvr.2024.104686","url":null,"abstract":"<div><p>Pulmonary hypertension (PH) is a chronic, progressive condition in which respiratory muscle dysfunction is a primary contributor to exercise intolerance and dyspnea in patients. Contractile function, blood flow distribution, and the hyperemic response are altered in the diaphragm with PH, and we sought to determine whether this may be attributed, in part, to impaired vasoreactivity of the resistance vasculature. We hypothesized that there would be blunted endothelium-dependent vasodilation and impaired myogenic responsiveness in arterioles from the diaphragm of PH rats. Female Sprague-Dawley rats were randomized into healthy control (HC, <em>n</em> = 9) and monocrotaline-induced PH rats (MCT, n = 9). Endothelium-dependent and -independent vasodilation and myogenic responses were assessed in first-order arterioles (1As) from the medial costal diaphragm in vitro. There was a significant reduction in endothelium-dependent (via acetylcholine; HC, 78 ± 15% vs. MCT, 47 ± 17%; <em>P</em> &lt; 0.05) and -independent (via sodium nitroprusside; HC, 89 ± 10% vs. MCT, 66 ± 10%; <em>P</em> &lt; 0.05) vasodilation in 1As from MCT rats. MCT-induced PH also diminished myogenic constriction (P &lt; 0.05) but did not alter passive pressure responses. The diaphragmatic weakness, impaired hyperemia, and blood flow redistribution associated with PH may be due, in part, to diaphragm vascular dysfunction and thus compromised oxygen delivery which occurs through both endothelium-dependent and -independent mechanisms.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"154 ","pages":"Article 104686"},"PeriodicalIF":3.1,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140786716","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":"Prognostic impact of coronary microvascular dysfunction in patients with atrial fibrillation","authors":"Ayman A. Mohammed ,&nbsp;Siqi Li ,&nbsp;Hengbin Zhang ,&nbsp;Fuad A. Abdu ,&nbsp;Abdul-Quddus Mohammed ,&nbsp;Wen Zhang ,&nbsp;Ekhlas Mahmoud Al-Hashedi ,&nbsp;Yawei Xu ,&nbsp;Wenliang Che","doi":"10.1016/j.mvr.2024.104685","DOIUrl":"https://doi.org/10.1016/j.mvr.2024.104685","url":null,"abstract":"<div><h3>Background</h3><p>Coronary microvascular dysfunction (CMD) is frequently observed in atrial fibrillation (AF), the most commonly sustained arrhythmia. Nevertheless, an in-depth prognostic significance of CMD in AF is lacking. We aimed to provide insight into the predictive impact of CMD assessed by a novel non-invasive coronary angiography-derived index of microcirculatory resistance (caIMR) for major adverse events (MACE) in AF patients.</p></div><div><h3>Method</h3><p>This study included patients with AF who underwent invasive coronary angiography due to suspected cardiac ischemia and did not exhibit obstructive epicardial coronary artery disease (≤50 % stenosis). The caIMR was prospectively evaluated, and the optimal cutoff value for predicting MACE was determined through ROC analysis.</p></div><div><h3>Result</h3><p>A total of 463 patients with AF were enrolled. During a median of 33 months of follow-up, 111 (23.97 %) patients had MACE endpoints. The best caIMR cutoff value was 39.28. In patients with MACE, both the mean caIMR and the prevalence of elevated caIMR (caIMR&gt;39.28) were significantly higher compared to those without MACE. An elevated caIMR was linked to a higher risk of MACE (log-rank <em>P</em> &lt; 0.001) and emerged as an independent predictor of clinical outcomes (HR: 4.029; 95 % CI: 2.529–6.418; <em>P</em> &lt; 0.001). In addition, the risk of MACE was higher in high caIMR patients with non-paroxysmal AF (log-rank P &lt; 0.001) and no catheter ablation (log-rank P &lt; 0.001).</p></div><div><h3>Conclusion</h3><p>Elevated caIMR is common and showed a vital independent prognostic significance in AF patients. In addition to well-known risk factors, assessment of microvascular function can be a feasible approach for early prevention and a therapeutic target in AF patients.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"154 ","pages":"Article 104685"},"PeriodicalIF":3.1,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140548836","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":"Biomarkers of endothelial glycocalyx damage are associated with microvascular dysfunction in resuscitated septic shock patients","authors":"Nazir Soubihe Neto,&nbsp;Marcela Curci Vieira de Almeida,&nbsp;Helton de Oliveira Couto,&nbsp;Carlos Henrique Miranda","doi":"10.1016/j.mvr.2024.104683","DOIUrl":"10.1016/j.mvr.2024.104683","url":null,"abstract":"<div><h3>Background</h3><p>Microvascular dysfunction plays a central role in organ dysfunction during septic shock. Endothelial glycocalyx (eGC) damage could contribute to impaired microcirculation. The aim was to assess whether several eGC-damaged biomarkers are associated with microvascular dysfunction in resuscitated septic shock patients.</p></div><div><h3>Methods</h3><p>This cross-sectional study included resuscitated septic shock patients (N = 31), and a group of healthy individuals (N = 20). The eGC damage biomarkers measured were syndecan-1 (SDC-1), soluble CD44 (CD44s), hyaluronic acid (HYAL) in blood sample; sulfated glycosaminoglycans (GAGs) in urine sample; and thrombomodulin (TBML) in blood sample as biomarker of endothelial cell damage. Microcirculation was assessed through sublingual videocapillaroscopy using the GlycoCheck™, which estimated the perfused vascular density (PVD); the perfused boundary region (PBR), an inverse parameter of the eGC thickness; and the microvascular health score (MVHS). We defined a low MVHS (&lt;50th percentile in septic patients) as a surrogate for more impaired microvascular function.</p></div><div><h3>Results</h3><p>The SDC-1, CD44s, TBML and GAGs levels were correlated with impaired microvascular parameters (PVD of vessels with diameter &lt; 10 μm, MVHS and flow-adjusted PBR); p &lt; 0.05 for all comparisons, except for GAGs and flow-adjusted PBR. The SDC-1 [78 ng/mL (interquartile range (IQR) 45–336) vs. 48 ng/mL (IQR 9–85); p = 0.052], CD44s [796ρg/mL (IQR 512–1995) vs. 526ρg/mL (IQR 287–750); p = 0.036], TBML [734ρg/mL (IQR 237–2396) vs. 95ρg/mL (IQR 63–475); p = 0.012] and GAGs levels [0.42 ρg/mg (IQR 0.04–1.40) vs. 0.07 ρg/mg (IQR 0.02–0.20); p = 0.024]; were higher in septic patients with more impaired sublingual microvascular function (low MVHS vs. high MVHS).</p></div><div><h3>Conclusion</h3><p>SDC-1, CD44s, TBML and GAGs levels were associated with impaired microvascular function in resuscitated septic shock patients.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"154 ","pages":"Article 104683"},"PeriodicalIF":3.1,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207277","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":"Comparative evaluation of trypsin and elastase digestion techniques for isolation of murine retinal vasculature","authors":"Anamika Sharma,&nbsp;Dhiraj Kumar Gupta,&nbsp;Shivantika Bisen,&nbsp;Nikhlesh K. Singh","doi":"10.1016/j.mvr.2024.104682","DOIUrl":"10.1016/j.mvr.2024.104682","url":null,"abstract":"<div><p>Dysfunctional pericytes and disruption of adherens or tight junctions are related to many microvascular diseases, including diabetic retinopathy. In this context, visualizing retinal vascular architecture becomes essential for understanding retinal vascular disease pathophysiology. Although flat mounts provide a demonstration of the retinal blood vasculature, they often lack a clear view of microaneurysms and capillary architecture. Trypsin and elastase digestion are the two techniques for isolating retinal vasculatures in rats, mice, and other animal models. Our observations in the present study reveal that trypsin digestion impacts the association between pericytes and endothelial cells. In contrast, elastase digestion effectively preserves these features in the blood vessels. Furthermore, trypsin digestion disrupts endothelial adherens and tight junctions that elastase digestion does not. Therefore, elastase digestion emerges as a superior technique for isolating retinal vessels, which can be utilized to collect reliable and consistent data to comprehend the pathophysiology of disorders involving microvascular structures.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"154 ","pages":"Article 104682"},"PeriodicalIF":3.1,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194162","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":"Contribution of platelets to disruption of the blood-brain barrier during arterial baroreflex dysfunction","authors":"Bowen Shen ,&nbsp;Lili Yang ,&nbsp;Xiaoli Jia ,&nbsp;Deping Kong ,&nbsp;Lei Jing ,&nbsp;Yongfeng Gao ,&nbsp;Shan Gao ,&nbsp;Ruimin Chen ,&nbsp;Fengbao Chen ,&nbsp;Chunyu Zhao ,&nbsp;Yue Li ,&nbsp;Rui Tan ,&nbsp;Xiaomin Zhao","doi":"10.1016/j.mvr.2024.104681","DOIUrl":"10.1016/j.mvr.2024.104681","url":null,"abstract":"<div><h3>Background</h3><p>Arterial baroreflex dysfunction, like many other central nervous system disorders, involves disruption of the blood-brain barrier, but what causes such disruption in ABR dysfunction is unclear. Here we explored the potential role of platelets in this disruption.</p></div><div><h3>Methods</h3><p>ABR dysfunction was induced in rats using sinoaortic denervation, and the effects on integrity of the blood-brain barrier were explored based on leakage of Evans blue or FITC-dextran, while the effects on expression of CD40L in platelets and of key proteins in microvascular endothelial cells were explored using immunohistochemistry, western blotting and enzyme-linked immunosorbent assay. Similar experiments were carried out in rat brain microvascular endothelial cell line, which we exposed to platelets taken from rats with ABR dysfunction.</p></div><div><h3>Results</h3><p>Sinoaortic denervation permeabilized the blood-brain barrier and downregulated zonula occludens-1 and occludin in rat brain, while upregulating expression of CD40L on the surface of platelets and stimulating platelet aggregation. Similar effects of permeabilization and downregulation were observed in healthy rats that received platelets from animals with ABR dysfunction, and in rat brain microvascular endothelial cells, but only in the presence of lipopolysaccharide. These effects were associated with activation of NF-κB signaling and upregulation of matrix metalloprotease-9. These effects of platelets from animals with ABR dysfunction were partially blocked by neutralizing antibody against CD40L or the platelet inhibitor clopidogrel.</p></div><div><h3>Conclusion</h3><p>During ABR dysfunction, platelets may disrupt the blood-brain barrier when CD40L on their surface activates NF-kB signaling within cerebral microvascular endothelial cells, leading to upregulation of matrix metalloprotease-9. Our findings imply that targeting CD40L may be effective against cerebral diseases involving ABR dysfunction.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"154 ","pages":"Article 104681"},"PeriodicalIF":3.1,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S002628622400030X/pdfft?md5=9292bfa1e8e1e434fb6539b334f66e8f&pid=1-s2.0-S002628622400030X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143764","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}