Microvascular research最新文献

{"title":"Retinal blood flow in eyes with primary open-angle glaucoma using a new Adaptive Optics Laser Doppler Velocimeter device","authors":"Ohud Altuwaym ,&nbsp;Martial Geiser ,&nbsp;Thibaud Mautuit ,&nbsp;Frédéric Truffer ,&nbsp;Christophe Chiquet","doi":"10.1016/j.mvr.2025.104858","DOIUrl":"10.1016/j.mvr.2025.104858","url":null,"abstract":"<div><h3>Purpose</h3><div>To measure retinal blood flow (RBF) in the retinal veins of patients with primary open-angle glaucoma (POAG) and to compare it with healthy controls. A secondary objective was to determine any correlation between RBF and visual field (VF) loss or retinal nerve-fiber layer (RNFL) thickness.</div></div><div><h3>Method</h3><div>Twelve patients with POAG and 11 healthy controls were included in a prospective single-center study. Our prototype Adaptive Optics Laser Doppler Velocimeter (AO-LDV) consisted of a laser Doppler velocimeter combined with an adaptive optic fundus camera (rtx1, Imagine Eyes®) allowing measurement of blood vessel diameter and therefore, calculation of blood flow within the vessel. Blood flow in the superior temporal vein (STV) was compared with that in the inferior temporal vein (ITV). All subjects underwent eye examinations including visual field (Humphrey 24-2 SITA-standard strategy) and measurement of retinal nerve-fiber layer (RNFL) thickness using a Cirrus HD-OCT (optic disc 200 × 200 cube) protocol. Sectoral structure-function relationships were studied in the glaucoma group.</div></div><div><h3>Results</h3><div>The velocity in the STV was lower in the glaucoma group (6.30 ± 1.6 mm/s) compared to the control group (8.6 ± 2.8 mm/s, <em>p</em> = 0.07), with no significant differences in the ITV. There were no significant differences in STV or ITV diameters between the groups. We found no relationship between either STV or ITV retinal blood flow and visual field or RNFL thickness.</div></div><div><h3>Conclusion</h3><div>Our prototype AO-LDV allowed accurate measurement of RBF in patients with glaucoma and showed that RBF was not reduced in the early or moderate stages of glaucoma. These preliminary results should be confirmed in a larger study, especially in late-stage glaucoma.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"162 ","pages":"Article 104858"},"PeriodicalIF":2.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873921","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":"PCSK9 inhibitor improved cardiac function after acute myocardial infarction in rats","authors":"Hongjin An ,&nbsp;Junju Zhu ,&nbsp;Qianqian Li","doi":"10.1016/j.mvr.2025.104847","DOIUrl":"10.1016/j.mvr.2025.104847","url":null,"abstract":"<div><h3>Background</h3><div>This study investigated the effects and possible mechanisms of Protein expression of protein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab on cardiac function in rats with acute myocardial infarction (AMI).</div></div><div><h3>Methods</h3><div>The AMI model was established by ligating the left anterior descending coronary artery in rats. The mRNA expression of PCSK9 in myocardial tissues was detected by real-time fluorescent quantitative PCR (RT-qPCR). Echocardiography was used to examine the cardiac function indexes. Hematoxylin-eosin (HE) and Masson stainings were used to detect myocardial pathologic injury. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to detect myocardial infarction area. Serum levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), lactate dehydrogenase (LDH), creatine kinase isoenzymes (CK-MB), cardiac troponin T (cTnT), interleukin-1β (IL-1β), interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) were detected by ELISA. CD31 and vascular endothelial growth factor (VEGF) positive expression was detected by immunohistochemistry. Protein expression levels of PCSK9, Bax, Bcl-2, cleaved-caspase3, receptor interacting protein kinase 1 (RIPK1), RIPK3, mixed lineage kinase domain-like (MLKL), and p-MLKL were detected in myocardial tissues by western blot.</div></div><div><h3>Results</h3><div>The mRNA level and protein expression of PCSK9 were significantly increased in AMI rats. PCSK9 inhibitor evolocumab reduced the levels of LDL-C and TC in serum, thereby improving dyslipidemia. And, evolocumab up-regulated the levels of left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), and down-regulated the levels of left ventricular end systolic diameter (LVESD), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic volume (LVESV), and left ventricular end diastolic volume (LVEDV), which in turn improved cardiac function. In addition, evolocumab attenuated myocardial pathological injury, reduced myocardial infarction area, lowered the levels of LDH, CK-MB, cTnT, IL-1β, IL-17, and TNF-α, and inhibited apoptosis rate, down-regulated Bax, cleaved-caspase3, RIPK1, RIPK3, MLKL, p-MLKL expression, and up-regulated Bcl-2 protein expression, CD31 and VEGF positive expression.</div></div><div><h3>Conclusion</h3><div>The PCSK 9 inhibitor evolocumab improved cardiac function in AMI rats, and the mechanism may be related to the RIPK1/RIPK3/MLKL pathway.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"162 ","pages":"Article 104847"},"PeriodicalIF":2.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718116","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":"Assessing coronary microvascular dysfunction in refractory no-reflow: Insights from dynamic myocardial perfusion scintigraphy and cardiac MRI","authors":"Stanislav Dil,&nbsp;Vyacheslav Ryabov,&nbsp;Leonid Maslov,&nbsp;Olga Mochula,&nbsp;Andrey Mochula,&nbsp;Maria Kercheva,&nbsp;Konstantin Zavadovsky,&nbsp;Evgeny Vyshlov","doi":"10.1016/j.mvr.2025.104862","DOIUrl":"10.1016/j.mvr.2025.104862","url":null,"abstract":"<div><h3>Background</h3><div>Refractory no-reflow correlates with worse outcomes, including larger infarct sizes, impaired ventricular function, and higher mortality rates, despite advances in percutaneous coronary intervention (PCI). Microvascular obstruction (MVO) and increased left ventricular end-diastolic pressure (LVEDP) are implicated in the pathogenesis, potentially exacerbating ischemic injury and limiting myocardial recovery. While pressure-wire–derived indices such as the Index of Microcirculatory Resistance (IMR) have been validated against MRI-defined MVO in STEMI populations, their invasive nature and procedural complexity limit broad adoption. In contrast, combining dynamic SPECT and cardiac MRI enables a comprehensive non-invasive functional-structural evaluation of coronary microvascular function in refractory no-reflow.</div></div><div><h3>Methods</h3><div>This study is a post hoc analysis of a larger randomized controlled trial (RCT) evaluating the efficacy and safety of intracoronary epinephrine in patients with refractory no-reflow post-PCI (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> <span><span>NCT04573751</span><svg><path></path></svg></span>). We evaluated global coronary flow metrics (RMBF, SMBF, gRFI) derived from SPECT and assessed structural markers of microvascular injury (infarct size, MVO) on MRI. Echocardiographic estimations of LVEDP were also analyzed.</div></div><div><h3>Results</h3><div>Dynamic SPECT revealed suboptimal stress myocardial blood flow in most patients, highlighting microvascular impairment. Elevated estimated LVEDP was significantly correlated with indexed MVO (rs = 0.678, <em>p</em> = 0.001). Traditional flow reserve metrics showed limited sensitivity, whereas global relative flow increase (gRFI) showed a statistically significant correlation with MVO, highlighting its added value in detecting stress-induced perfusion abnormalities. Given the small sample and potential outlier influence, this observation should be considered hypothesis-generating.</div></div><div><h3>Conclusion</h3><div>Our findings support that functional impairments—particularly elevated LVEDP and reduced gRFI—are associated with refractory no-reflow. In particular, gRFI may serve as a promising non-invasive marker of microvascular dysfunction, complementing structural imaging. None-theless, further validation in larger cohorts is needed. This study advocates for refined multimodal imaging strategies and tailored therapeutic approaches targeting dynamic microvascular disturbances to improve outcomes in refractory no-reflow.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"162 ","pages":"Article 104862"},"PeriodicalIF":2.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895821","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 theoretical model for oxygen transport to the cerebral cortex: effects of flow redistribution by penetrating arterioles","authors":"Akshita Sharma ,&nbsp;Timothy W. Secomb","doi":"10.1016/j.mvr.2025.104836","DOIUrl":"10.1016/j.mvr.2025.104836","url":null,"abstract":"<div><div>The goal of this study is to analyze the effects of changes of blood flow in penetrating arterioles (PAs) on the spatial distribution of tissue oxygen levels in the cerebral cortex. A theoretical model is used to simulate blood flow and oxygen transport in the cortical microcirculation. Networks containing up to 20,000 vessel segments, covering regions up to 1.1 mm², are generated by combining multiple hexagonal units, each fed by one PA. Varying numbers of adjacent PAs are constricted to 50 % of their original diameters, resulting in PA flow reduction by 93 %. With constriction of one or two PAs, the predicted minimum oxygen partial pressure is in the range 10–20 mmHg, corresponding to mild hypoxia. When three or more adjacent PAs are constricted, severe hypoxia (partial pressure below 10 mmHg) is predicted. Thus, oxygenation of the cortex is predicted to be only mildly affected by flow reduction in isolated PAs, but vulnerable to flow reduction in multiple adjacent PAs. Further simulations are used to explore the effects of flow redistribution while holding overall perfusion constant. If one PA is constricted and one adjacent PA is dilated, mild hypoxia is present. With three PAs constricted and four adjacent PAs dilated, regions of both mild and severe hypoxia are predicted. These results show that redistribution of blood flow, caused for instance by disruption of mechanisms for local blood flow regulation, can result in tissue hypoxia, even in the absence of reduced perfusion.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104836"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144518521","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":"Letter to the editor: “Pitfalls in the assessment of microcirculation”","authors":"Arnaldo Dubin","doi":"10.1016/j.mvr.2025.104841","DOIUrl":"10.1016/j.mvr.2025.104841","url":null,"abstract":"","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104841"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572148","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":"Quantitative image analysis of nailfold capillaries during an in-hospital education program for type 2 diabetes or obesity","authors":"Kengo Miyoshi ,&nbsp;Masatomo Chikamori ,&nbsp;Takashi Ando ,&nbsp;Kengo Nakata ,&nbsp;Tomohisa Aoyama ,&nbsp;Yukiko T. Matsunaga ,&nbsp;Toshimasa Yamauchi","doi":"10.1016/j.mvr.2025.104830","DOIUrl":"10.1016/j.mvr.2025.104830","url":null,"abstract":"<div><div>Nailfold capillaries are small U-shaped vessels located beneath the skin at the proximal part of the fingernail, and their morphology changes owing to various diseases. This study quantitatively analyzed nailfold capillaries using microscopy in patients hospitalized for 2 weeks for education and treatment of type 2 diabetes (T2D) or obesity. Our results suggest that nailfold arterial diameter and smoking history are useful predictors of diabetic neuropathy. An elevated urinary albumin-to-creatinine ratio correlated with decreased venous diameter during hospitalization, reflecting latent intravascular hypoalbuminemia in patients with diabetic nephropathy. Both body mass index and short-term weight reduction during hospitalization correlated with the color contrast between the capillaries and the perivascular zone, defined as delta E. These results suggest that the morphology of nailfold capillaries in T2D and obesity could be useful indicators of diabetic neuropathy and nephropathy, with delta E being a useful indicator of extracellular water volume in these populations. This is the first study to observe short-term changes in nailfold capillary morphology in relation to interventions for lifestyle-related diseases.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104830"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144255406","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 electrophysiological effects of angiotensin 1–7 on hypertrophic myocardium in spontaneously hypertensive rats","authors":"Xin Yu ,&nbsp;Zhen Yang ,&nbsp;Zhilan Ma ,&nbsp;Ru Yan ,&nbsp;Jianzhong Zhang","doi":"10.1016/j.mvr.2025.104843","DOIUrl":"10.1016/j.mvr.2025.104843","url":null,"abstract":"<div><div>This study aimed to explore the effects of Angiotensin 1–7 (Ang1–7) on electrophysiological remodeling of hypertensive hypertrophic myocardium in spontaneously hypertensive rats (SHR). Thirty male SHR rats were equally divided into three groups: SHR control group (SHR<img>C) treated with saline; Ang1–7 group (SHR-A) treated with Ang1–7[25 μg·(kg min)⁻¹] and Ang1–7 blocker group (SHR<img>B) treated with A779 [72 μg·(kg min)⁻¹]. Wistar-Kyoto (WKY) rats (<em>n</em> = 10) were used as a normotensive group. The treatment period was 5 weeks. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. Echocardiography was used to evaluate cardiac function. The ventricular myocytes were isolated for evaluation of electrophysiological remodeling of myocardium using microelectrode and patch clamp techniques. When compared with those in WKY rats before treatment, systolic and diastolic pressures were significantly higher in SHR (<em>P</em> &lt; 0.01 and <em>P</em> &lt; 0.001 respectively), left ventricular end-diastolic diameter (LVEDd) was significantly lower (<em>P</em> &lt; 0.05), while diastolic interventricular septum thickness (IVSd), diastolic left ventricular posterior wall thickness (LVPWd) were significantly greater in SHR (<em>P</em> &lt; 0.01). After 5 weeks of treatment, compared with SHR-C group, SBP, DBP, IVSd, LVPWd in SHR-A group were lower significantly (<em>P</em> &lt; 0.05), while SBP in SHR-B group was significantly higher (<em>P</em> &lt; 0.05). Compared with WKY group, the resting potential (RP), action potential amplitude (APA) and transient sodium current (<em>I</em>_Na-T) in SHR group were significantly lower (<em>P</em> &lt; 0.05), and the action potential duration (APD₂₀, APD₅₀ and APD₉₀) in SHR group was greater (<em>P</em> &lt; 0.05). After Ang1–7 intervention, RP, APA and <em>I</em>_Na-T were significantly greater in SHR-A than those in SHR-C (<em>P</em> &lt; 0.05), and APD in SHR-A significantly lower than that in SHR-C (<em>P</em> &lt; 0.05). Taken together, these results demonstrated that Ang1–7 can not only decrease the blood pressure, but reverse the myocardial hypertrophy and electrophysiological remodeling as well in SHR rats.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104843"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642932","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":"Predictive value of the average three-vessel microvascular resistance in patients with non-ST-segment elevation myocardial infarction after percutaneous coronary intervention","authors":"Ruijin Hong ,&nbsp;Beilei Li ,&nbsp;Hui Chen ,&nbsp;Jiaxin Zhong ,&nbsp;Yuxiang Chen ,&nbsp;Yuanming Yan ,&nbsp;Lianglong Chen ,&nbsp;Qin Chen ,&nbsp;Yukun Luo","doi":"10.1016/j.mvr.2025.104838","DOIUrl":"10.1016/j.mvr.2025.104838","url":null,"abstract":"<div><h3>Objectives</h3><div>We investigated the predictive value of the average microvascular resistance of the three main vessels (3VA-AMR) for the prognosis of patients with non-ST-segment elevation myocardial infarction (NSTEMI) after percutaneous coronary intervention (PCI).</div></div><div><h3>Methods</h3><div>This study was conducted on patients with NSTEMI who underwent PCI between March 1, 2021, and February 28, 2022, at Fujian Medical University Union Hospital. Quantitative flow ratio (QFR) analysis was conducted on all patients' PCI angiography images to assess postoperative QFR and angio-based microvascular resistance (AMR) for three main vessels. All enrolled patients were devided into two groups based on the criteria for coronary microvascular dysfunction (CMD): high 3VA-AMR group and low 3VA-AMR group. The primary outcome was 2-year major adverse cardiac events (MACEs), including cardiovascular death, myocardial infarction, and ischemia-driven revascularization.</div></div><div><h3>Results</h3><div>A total of 290 patients were included in the final analysis. Compared with the low 3VA-AMR group, the three vessels of high 3VA-AMR group showed lower area stenosis (49.46 ± 13.70 % vs. 52.93 ± 15.43 %，<em>P</em> = 0.001), higher QFR value (0.92 ± 0.05 vs. 0.88 ± 0.09, P &lt; 0.001), and higher AMR value (274.50 [257.33–301.42] mmHg*s/m vs. 208.00 [182.00–231.83] mmHg*s/m, P &lt; 0.001). The incidence of 2-year MACEs was significantly higher in the high 3VA-AMR group than in the low 3VA-AMR group (21.90 % vs. 10.27 %, <em>P</em> = 0.007). Univariate and multivariate Cox regression analyses confirmed that 3VA-AMR was independently associated with 2-year MACEs (HR:1.007, 95 % CI:1.004–1.010, <em>P</em> &lt; 0.001). The Kaplan–Meier method further confirmed the difference in 2-year MACE risk between two groups. Receiver operating characteristic curve analysis showed a significant correlation between 3VA-AMR and MACE (area under the curve: 0.701, <em>P</em> &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>3VA-AMR was an independent risk factor for 2-year MACEs in NSTEMI patients. Compared with target-vessel AMR, 3VA-AMR demonstrated superior predictive value for 2-year MACEs following PCI.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104838"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528670","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":"Structural and causal links between retinal vascular geometry and neural layer thickness","authors":"Mayinuer Yusufu ,&nbsp;Robert N. Weinreb ,&nbsp;Mengtian Kang ,&nbsp;Algis J. Vingrys ,&nbsp;Xianwen Shang ,&nbsp;Lei Zhang ,&nbsp;Danli Shi ,&nbsp;Mingguang He","doi":"10.1016/j.mvr.2025.104834","DOIUrl":"10.1016/j.mvr.2025.104834","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate structural relationships between retinal vasculometry from color fundus photography (CFP) and neural layers obtained from Optical Coherence Tomography (OCT) scans.</div></div><div><h3>Methods</h3><div>This cross-sectional study used the Retina-based Microvascular Health Assessment System (RMHAS) to extract retinal vascular measurements in the 6*6 mm area centered on the macular region and analyzed their associations with OCT parameters. We investigated both pairwise correlations between individual retinal layers and vascular parameters and associations between sets of variables. Mendelian randomization was employed to investigate potential causality.</div></div><div><h3>Results</h3><div>Data from 67,918 eyes of 43,029 participants were included. Among neural layers, Ganglion Cell-Inner Plexiform Layer (GC-IPL) showed the most notable correlations with vascular Density and Complexity (<em>r</em> = 0.199 for arterial Vessel Area Density and <em>r</em> = 0.175 for Number of Segments). Inner Nuclear Layer (INL) thickness correlated with Width (<em>r</em> = 0.122) and arterial Vessel Area Density (<em>r</em> = 0.127). Mendelian randomization indicated a bidirectional causal relationship. Genetically predicted higher Vessel Density was associated with increased thickness across various retinal layers, with standardized effect size of 1.50 on Inner Segment/Outer Segment + Photoreceptor Segment thickness. Genetically predicted increases in retinal layer thicknesses, particularly the Outer Plexiform Layer, were linked to higher Vessel Density (standardized effect size 0.45) and Fractal Dimension (standardized effect size 0.48).</div></div><div><h3>Conclusions</h3><div>GC-IPL and INL were positively associated with vascular Density and Caliber. Multidimensional relationships indicate a complementary nature between retinal vascular and neural parameters, highlighting their value as a composite biomarker. Mendelian Randomization uncovered a bidirectional causal relationship, providing insights into novel therapeutic approaches targeting vascular and neuronal components.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104834"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144522807","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":"DDIT4 knockdown suppresses venous malformation progression by inhibiting NF-κB signaling as a potential therapeutic target","authors":"Yang He ,&nbsp;Jian Lin ,&nbsp;Yi Li ,&nbsp;Xiaobo Cheng ,&nbsp;Tong Wang ,&nbsp;Wei Wang ,&nbsp;Weixing Zeng ,&nbsp;Yongsheng Li","doi":"10.1016/j.mvr.2025.104833","DOIUrl":"10.1016/j.mvr.2025.104833","url":null,"abstract":"<div><h3>Background</h3><div>This study aims to investigate the regulatory role and underlying molecular mechanisms of DNA Damage Inducible Transcript 4 (DDIT4) in the pathogenesis of Venous Malformations (VMs), providing foundational experimental evidence for potential targeted therapies.</div></div><div><h3>Methods</h3><div>Bioinformatic analysis identified <em>DDIT4</em> as a key differentially expressed gene in VMs, and the sgGSEA method was employed to predict its potential biological functions. Immunohistochemical staining and immunofluorescence were performed to validate the expression level of DDIT4 and its association with vascular density. A lentiviral VMs cell model was established to assess DDIT4 expression levels. The effects of DDIT4 knockdown on VMs cell function were evaluated, with mechanistic insights gained through transcriptome sequencing and Western blot analysis. Further validation was performed using 3D VMs cell models and nude mouse xenografts with DDIT4 knockdown. Additionally, exogenous functional rescue experiments were conducted by activating the NF-κB pathway with lipopolysaccharide (LPS) in DDIT4 knockdown VMs 3D cell models and nude mouse xenografts to further investigate the role of DDIT4.</div></div><div><h3>Results</h3><div>DDIT4 was upregulated in VMs tissues and correlated with angiogenesis. DDIT4 knockdown increased cell roundness, inhibited proliferation, migration, and NF-κB pathway activation, and blocked angiogenesis in VMs 3D models and lesion formation in nude mouse xenografts, while suppressing the NF-κB pathway in both. NF-κB pathway activation restored angiogenesis in both models.</div></div><div><h3>Conclusions</h3><div>DDIT4 knockdown inhibits VMs progression by suppressing the NF-κB pathway, suggesting that DDIT4 may serve as a potential therapeutic target.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104833"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506523","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}