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.
{"title":"Quantitative image analysis of nailfold capillaries during an in-hospital education program for type 2 diabetes or obesity","authors":"Kengo Miyoshi , Masatomo Chikamori , Takashi Ando , Kengo Nakata , Tomohisa Aoyama , Yukiko T. Matsunaga , 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":"2025-06-07","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}
To investigate the changes in the morphology of nailfold capillaries in patients with retinal vein occlusion (RVO) and their relationship with retinal vessel density (RVD).
Methods
This cross-sectional study, included 30 patients with RVO and 30 normal controls. Nailfold capillaroscopy was used to evaluate the morphology of the nailfold capillaries, and optical coherence tomography angiography was used to evaluate RVD.
Results
Abnormal morphological features of nailfold capillaries, including lower capillary density (p < 0.001), more tortuous capillaries (p = 0.003), more capillary dilation >25 μm (p = 0.001), and more avascular areas >200/μm (p < 0.001), were more common in patients with RVO than in normal controls. Compared to the normal eye, the affected eyes of patients with RVO showed lower RVD in the superficial vascular plexus (SCP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP). There following correlations between abnormal nailfold capillaries and RVD in affected eyes of RVO patients were observed: the number of nailfold capillary hemorrhages was negatively associated with RVD in the SCP (ρ = −0.376, p = 0.046) and ICP (ρ = −0.506, p = 0.004); the number of dilated capillaries >25 μm was negatively associated with RVD in the ICP (ρ = −0.389, p = 0.033); and the number of avascular zones >200/μm was negatively associated with RVD in the DCP (ρ = −0.374, p = 0.041).
Conclusions
Patients with RVO have abnormal morphology of the nailfold capillaries. In addition, nailfold capillary changes are correlated with RVD, suggesting that systemic microcirculatory abnormalities may be associated with RVO.
目的探讨视网膜静脉闭塞（RVO）患者甲襞毛细血管形态的变化及其与视网膜血管密度（RVD）的关系。方法采用横断面研究，选取30例RVO患者和30例正常对照。甲襞毛细血管镜检查评估甲襞毛细血管形态，光学相干断层扫描血管造影评估RVD。结果甲襞毛细血管形态异常，包括毛细血管密度降低(p <；0.001)，更弯曲的毛细血管（p = 0.003），更多的毛细血管扩张>；25 μm (p = 0.001)，更多的无血管区域>；200/μm (p <；0.001)，在RVO患者中比在正常对照中更常见。与正常眼相比，RVO患者患眼的浅血管丛（SCP）、中毛细血管丛（ICP）和深毛细血管丛（DCP）的RVD均较低。RVO患者患眼甲襞毛细血管异常与RVD的相关性为：SCP （ρ = - 0.376, p = 0.046）和ICP （ρ = - 0.506, p = 0.004）中甲襞毛细血管出血数与RVD呈负相关；25 μm的扩张毛细血管数量与ICP内RVD呈负相关（ρ = - 0.389, p = 0.033）；无血管带数>；200/μm与DCP的RVD呈负相关（ρ = - 0.374, p = 0.041）。结论RVO患者甲襞毛细血管形态异常。此外，甲襞毛细血管变化与RVD相关，提示全身微循环异常可能与RVO有关。
{"title":"Nailfold capillary morphology changes in patients with retinal vein occlusion","authors":"Wenbo Zhang, Hailong Wu, Yadi Zhang, Xiaopeng Gu, Hongping Nie, Yuan Wu","doi":"10.1016/j.mvr.2025.104822","DOIUrl":"10.1016/j.mvr.2025.104822","url":null,"abstract":"<div><h3>Aim</h3><div>To investigate the changes in the morphology of nailfold capillaries in patients with retinal vein occlusion (RVO) and their relationship with retinal vessel density (RVD).</div></div><div><h3>Methods</h3><div>This cross-sectional study, included 30 patients with RVO and 30 normal controls. Nailfold capillaroscopy was used to evaluate the morphology of the nailfold capillaries, and optical coherence tomography angiography was used to evaluate RVD.</div></div><div><h3>Results</h3><div>Abnormal morphological features of nailfold capillaries, including lower capillary density (<em>p</em> < 0.001), more tortuous capillaries (<em>p</em> = 0.003), more capillary dilation >25 μm (<em>p</em> = 0.001), and more avascular areas >200/μm (<em>p</em> < 0.001), were more common in patients with RVO than in normal controls. Compared to the normal eye, the affected eyes of patients with RVO showed lower RVD in the superficial vascular plexus (SCP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP). There following correlations between abnormal nailfold capillaries and RVD in affected eyes of RVO patients were observed: the number of nailfold capillary hemorrhages was negatively associated with RVD in the SCP (ρ = −0.376, <em>p</em> = 0.046) and ICP (ρ = −0.506, <em>p</em> = 0.004); the number of dilated capillaries >25 μm was negatively associated with RVD in the ICP (ρ = −0.389, <em>p</em> = 0.033); and the number of avascular zones >200/μm was negatively associated with RVD in the DCP (ρ = −0.374, <em>p</em> = 0.041).</div></div><div><h3>Conclusions</h3><div>Patients with RVO have abnormal morphology of the nailfold capillaries. In addition, nailfold capillary changes are correlated with RVD, suggesting that systemic microcirculatory abnormalities may be associated with RVO.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104822"},"PeriodicalIF":2.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144185234","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}
Pub Date : 2025-05-26DOI: 10.1016/j.mvr.2025.104821
Shali Xiang , Xuewen Tang
Myocardial ischemia reperfusion (I/R) injury is the main pathological manifestation of coronary artery disease closely linked with adverse cardiovascular outcomes. Aquaporin 1 (AQP1) is a water molecule that has been reported to be highly expressed during the process of myocardial I/R injury. The aim of this research was to explore the role of AQP1 in myocardial I/R injury and the relevant mechanism of action. RT-qPCR and western blotting were used to detect AQP1 expression. CCK-8 method was used to detect cell viability. JC-1 dye, MitoSox-Red staining and ATP-Red 1 probe were respectively used to detect mitochondrial membrane potential, mitochondrial ROS (mtROS) and ATP synthesis. C11-BODIPY 581/591 probe and FerroOrange probe were respectively used to measure lipid reactive oxygen species (ROS) and Fe(2+). Seahorse XFe96 Analyser was used to detect oxygen consumption rate (OCR). Assay kits were used to estimate mitochondrial permeability transition pore (mPTP) opening, total iron and lipid peroxidation levels. Western blotting was used to detect the expression of ferroptosis, energy metabolism and Wnt/β-catenin pathway-related proteins. AQP1 expression was elevated in hypoxia/reoxygenation (H/R)-exposed H9c2 cells. Deficient AQP1 promoted the viability, ameliorated mitochondrial dysfunction, ferroptosis and energy metabolism disorder in H/R-injured H9c2 cells. Further, AQP1 deletion might activate Wnt/β-catenin pathway and XAV939, an inhibitor of Wnt signaling pathway could partially revert the influences of AQP1 knockdown on the viability, mitochondrial function, ferroptosis and energy metabolism in H/R-treated H9c2 cells. To be concluded, AQP1 interference might protect against H/R-induced mitochondrial dysfunction, ferroptosis and energy metabolism disorder in H9c2 cells via modulating Wnt/β-catenin pathway.
{"title":"Interfering with AQP1 alleviates ferroptosis, improves mitochondrial function and energy metabolic disorder in hypoxia/reoxygenation-induced H9c2 cardiomyocytes via Wnt/β-catenin pathway","authors":"Shali Xiang , Xuewen Tang","doi":"10.1016/j.mvr.2025.104821","DOIUrl":"10.1016/j.mvr.2025.104821","url":null,"abstract":"<div><div>Myocardial ischemia reperfusion (I/R) injury is the main pathological manifestation of coronary artery disease closely linked with adverse cardiovascular outcomes. Aquaporin 1 (AQP1) is a water molecule that has been reported to be highly expressed during the process of myocardial I/R injury. The aim of this research was to explore the role of AQP1 in myocardial I/R injury and the relevant mechanism of action. RT-qPCR and western blotting were used to detect AQP1 expression. CCK-8 method was used to detect cell viability. JC-1 dye, MitoSox-Red staining and ATP-Red 1 probe were respectively used to detect mitochondrial membrane potential, mitochondrial ROS (mtROS) and ATP synthesis. C11-BODIPY 581/591 probe and FerroOrange probe were respectively used to measure lipid reactive oxygen species (ROS) and Fe(<sup>2+</sup>). Seahorse XFe96 Analyser was used to detect oxygen consumption rate (OCR). Assay kits were used to estimate mitochondrial permeability transition pore (mPTP) opening, total iron and lipid peroxidation levels. Western blotting was used to detect the expression of ferroptosis, energy metabolism and Wnt/β-catenin pathway-related proteins. AQP1 expression was elevated in hypoxia/reoxygenation (H/R)-exposed H9c2 cells. Deficient AQP1 promoted the viability, ameliorated mitochondrial dysfunction, ferroptosis and energy metabolism disorder in H/R-injured H9c2 cells. Further, AQP1 deletion might activate Wnt/β-catenin pathway and XAV939, an inhibitor of Wnt signaling pathway could partially revert the influences of AQP1 knockdown on the viability, mitochondrial function, ferroptosis and energy metabolism in H/R-treated H9c2 cells. To be concluded, AQP1 interference might protect against H/R-induced mitochondrial dysfunction, ferroptosis and energy metabolism disorder in H9c2 cells via modulating Wnt/β-catenin pathway.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104821"},"PeriodicalIF":2.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174179","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}
Pub Date : 2025-05-18DOI: 10.1016/j.mvr.2025.104820
Changsheng Chen , Xi Xu , Jiahao Lu , Yuqing Xiang , Linsheng Shi , Dong Liu
The blood-brain barrier (BBB) serves as a highly selective interface that regulates the transport of molecules between the blood and the brain. Its integrity is essential for maintaining neuronal homeostasis and preventing neuroinflammation. Hyperglycemia, a hallmark of diabetes, is linked to cognitive deficits and central nervous system (CNS) pathologies, including vascular dementia, stroke, and Alzheimer's disease, with BBB damage as a potential contributing factor. As the global prevalence of diabetes rises, understanding the connection between hyperglycemia and BBB dysfunction may facilitate the development of novel treatments that protect or restore BBB integrity, thereby alleviating the neurological complications of diabetes. Furthermore, it may aid in the development of targeted therapies for diabetes-related neurological complications. This literature review examines the emerging insights into the relationship between hyperglycemia and BBB dysfunction. It focuses on the mechanisms underlying BBB dysfunction, the clinical manifestations of this dysfunction in diabetes and cerebrovascular diseases, and potential therapeutic interventions.
{"title":"Hyperglycemia-induced blood-brain barrier dysfunction: Mechanisms and therapeutic interventions","authors":"Changsheng Chen , Xi Xu , Jiahao Lu , Yuqing Xiang , Linsheng Shi , Dong Liu","doi":"10.1016/j.mvr.2025.104820","DOIUrl":"10.1016/j.mvr.2025.104820","url":null,"abstract":"<div><div>The blood-brain barrier (BBB) serves as a highly selective interface that regulates the transport of molecules between the blood and the brain. Its integrity is essential for maintaining neuronal homeostasis and preventing neuroinflammation. Hyperglycemia, a hallmark of diabetes, is linked to cognitive deficits and central nervous system (CNS) pathologies, including vascular dementia, stroke, and Alzheimer's disease, with BBB damage as a potential contributing factor. As the global prevalence of diabetes rises, understanding the connection between hyperglycemia and BBB dysfunction may facilitate the development of novel treatments that protect or restore BBB integrity, thereby alleviating the neurological complications of diabetes. Furthermore, it may aid in the development of targeted therapies for diabetes-related neurological complications. This literature review examines the emerging insights into the relationship between hyperglycemia and BBB dysfunction. It focuses on the mechanisms underlying BBB dysfunction, the clinical manifestations of this dysfunction in diabetes and cerebrovascular diseases, and potential therapeutic interventions.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104820"},"PeriodicalIF":2.9,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144088816","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}
Pub Date : 2025-05-14DOI: 10.1016/j.mvr.2025.104819
Moa Nilsson , Martin Hultman , Freya Richter , Joakim Henricson , Marcus Larsson , Tomas Strömberg , Ingemar Fredriksson , Fredrik Iredahl
Introduction
Dysfunctional microcirculation is associated with cardiovascular risk factors, chronic disease such as diabetes and acute conditions like septic shock. The non-invasive optical techniques laser Doppler flowmetry (LDF) and diffuse reflectance spectroscopy (DRS) are often used to measure perfusion and oxygen saturation, but are limited to single-point measurements making them sensitive to spatial variations. The imaging modalities multi-exposure laser speckle contrast imaging (MELSCI) and multi-spectral imaging (MSI) overcome this limitation by capturing the parameters in a larger skin area.
Aim
To assess the day-to-day variability of speed-resolved perfusion and oxygen saturation in the forearm and plantar foot at baseline and peak response following arterial occlusion-release, while also evaluating sex and age influences.
Method
MELSCI and MSI were used on 48 participants (12 males and 12 females aged 20–30, and 12 males and 12 females aged 50–60) across two measurements within a week. Each measurement lasted 60 min, with perfusion and oxygen saturation being measured at baseline (10 min), during occlusion (5 min), and post-occlusion (5 min) as spatial averages over the entire imaged tissue area.
Results
Older age was associated with higher foot perfusion at peak (p = 0.006). Variability (CV) ranged from 1.4 % to 19 %, with foot low-speed perfusion showing a sex- and age-related difference at peak (p = 0.007).
Conclusion
Age and sex influenced microcirculatory parameters, aligning with prior research. MELSCI and MSI demonstrated low day-to-day variability, making them promising techniques for clinical disease monitoring. The variability of MELSCI perfusion was lower than previously reported for laser speckle contrast imaging (LSCI) perfusion.
{"title":"Day-to-day variability in cutaneous microcirculation measured with multi-exposure laser speckle contrast imaging and multispectral imaging","authors":"Moa Nilsson , Martin Hultman , Freya Richter , Joakim Henricson , Marcus Larsson , Tomas Strömberg , Ingemar Fredriksson , Fredrik Iredahl","doi":"10.1016/j.mvr.2025.104819","DOIUrl":"10.1016/j.mvr.2025.104819","url":null,"abstract":"<div><h3>Introduction</h3><div>Dysfunctional microcirculation is associated with cardiovascular risk factors, chronic disease such as diabetes and acute conditions like septic shock. The non-invasive optical techniques laser Doppler flowmetry (LDF) and diffuse reflectance spectroscopy (DRS) are often used to measure perfusion and oxygen saturation, but are limited to single-point measurements making them sensitive to spatial variations. The imaging modalities multi-exposure laser speckle contrast imaging (MELSCI) and multi-spectral imaging (MSI) overcome this limitation by capturing the parameters in a larger skin area.</div></div><div><h3>Aim</h3><div>To assess the day-to-day variability of speed-resolved perfusion and oxygen saturation in the forearm and plantar foot at baseline and peak response following arterial occlusion-release, while also evaluating sex and age influences.</div></div><div><h3>Method</h3><div>MELSCI and MSI were used on 48 participants (12 males and 12 females aged 20–30, and 12 males and 12 females aged 50–60) across two measurements within a week. Each measurement lasted 60 min, with perfusion and oxygen saturation being measured at baseline (10 min), during occlusion (5 min), and post-occlusion (5 min) as spatial averages over the entire imaged tissue area.</div></div><div><h3>Results</h3><div>Older age was associated with higher foot perfusion at peak (<em>p</em> = 0.006). Variability (CV) ranged from 1.4 % to 19 %, with foot low-speed perfusion showing a sex- and age-related difference at peak (<em>p</em> = 0.007).</div></div><div><h3>Conclusion</h3><div>Age and sex influenced microcirculatory parameters, aligning with prior research. MELSCI and MSI demonstrated low day-to-day variability, making them promising techniques for clinical disease monitoring. The variability of MELSCI perfusion was lower than previously reported for laser speckle contrast imaging (LSCI) perfusion.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104819"},"PeriodicalIF":2.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086444","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}
MicroRNAs (miRNAs), a class of non-coding RNAs, are pivotal post-transcriptional regulators of gene expression with profound implications in the pathogenesis of atherosclerosis (AS). As a progressive arterial disease driven by vascular cells dysfunction, lipid dysregulation and subsequent chronic inflammation, AS remains a leading cause of global morbidity. Recent studies have demonstrated how important miRNAs are in regulating central biological processes in the vascular wall, such as endothelial function, vascular smooth muscle cell (VSMC) phenotypic switching, and macrophage polarization. This review provides comprehensive insight into the role of miRNAs in the development and complexity of atherosclerotic plaques according to their effects on endothelial cells, macrophages, and VSMCs. We also go over the growing prospects of miRNAs as therapeutic targets and diagnostic biomarkers, providing information to be used in the study of vascular diseases. Lastly, we address recent complications and potential applications of miRNA-based approaches in clinical practice.
{"title":"MicroRNA regulatory dynamic, emerging diagnostic and therapeutic frontier in atherosclerosis","authors":"Syeda Armana Zaidi, Zhiyu Fan, Talha Chauhdari, Yongsheng Ding","doi":"10.1016/j.mvr.2025.104818","DOIUrl":"10.1016/j.mvr.2025.104818","url":null,"abstract":"<div><div>MicroRNAs (miRNAs), a class of non-coding RNAs, are pivotal post-transcriptional regulators of gene expression with profound implications in the pathogenesis of atherosclerosis (AS). As a progressive arterial disease driven by vascular cells dysfunction, lipid dysregulation and subsequent chronic inflammation, AS remains a leading cause of global morbidity. Recent studies have demonstrated how important miRNAs are in regulating central biological processes in the vascular wall, such as endothelial function, vascular smooth muscle cell (VSMC) phenotypic switching, and macrophage polarization. This review provides comprehensive insight into the role of miRNAs in the development and complexity of atherosclerotic plaques according to their effects on endothelial cells, macrophages, and VSMCs. We also go over the growing prospects of miRNAs as therapeutic targets and diagnostic biomarkers, providing information to be used in the study of vascular diseases. Lastly, we address recent complications and potential applications of miRNA-based approaches in clinical practice.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104818"},"PeriodicalIF":2.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947300","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}
Pub Date : 2025-05-07DOI: 10.1016/j.mvr.2025.104817
Jinhui Zhou , Chao Ni , Zhenquan Wang , Yuhan Xia , Hongying Shi , Xiaoshan Zhao , Yufei Chen , Chenchen Liu , Xing Rong , Rongzhou Wu , Maoping Chu , Huixian Qiu
Objective
Kawasaki disease (KD) is an acute systemic inflammation, that affects medium-sized arteries. Coronary artery lesions (CALs) were the most serious complication or sequelae of KD. The intense inflammatory response leads to platelet activation, further exacerbating inflammation, which plays an important role in the pathogenesis of CALs in KD patients. Plus, coagulation factors are closely related to platelet activation. Therefore, we speculate that the activated partial thromboplastin time (APTT), an indicator of coagulation factor function, may be involved in the occurrence of CALs, but it has not been explored yet. This study aims to investigate the effect of the APTT level on CALs occurrence in the acute phase of KD.
Methods
A total of 2303 KD patients during a 10-year period were recruited at the Wenzhou Medical University affiliated Yuying Children's Hospital. A total of 1715 patients who completed the follow-up were enrolled in the final analysis and were divided into the low APTT group and the high APTT group at a 46 s cutoff before receiving intravenous immunoglobulin (IVIG) treatment. Multiple logistic regression analysis and stratified analysis were utilized to evaluate the independent impact of APTT levels on the occurrence of CALs and to determine the impact of APTT levels on the occurrence of CALs in different subgroups, respectively.
Results
The incidence of CALs in the low APTT group and the high APTT group was 12.5 % and 17.5 %, respectively (P = 0.005). Patients with high APTT levels had higher CRP levels (P < 0.001). High APTT levels were the independent risk factor on the occurrence of CALs; the adjusted odds ratio (OR) was 1.523 (95 % CI: 1.144, 2.028). Similar results were found in stratification analysis and sensitivity analysis.
Conclusions
KD patients with high APTT levels (≥46 s) before IVIG treatment may be more prone to developing CALs in the acute phase of KD.
{"title":"Activated partial thromboplastin time levels and coronary artery lesions in Kawasaki disease: A retrospective cohort study","authors":"Jinhui Zhou , Chao Ni , Zhenquan Wang , Yuhan Xia , Hongying Shi , Xiaoshan Zhao , Yufei Chen , Chenchen Liu , Xing Rong , Rongzhou Wu , Maoping Chu , Huixian Qiu","doi":"10.1016/j.mvr.2025.104817","DOIUrl":"10.1016/j.mvr.2025.104817","url":null,"abstract":"<div><h3>Objective</h3><div>Kawasaki disease (KD) is an acute systemic inflammation, that affects medium-sized arteries. Coronary artery lesions (CALs) were the most serious complication or sequelae of KD. The intense inflammatory response leads to platelet activation, further exacerbating inflammation, which plays an important role in the pathogenesis of CALs in KD patients. Plus, coagulation factors are closely related to platelet activation. Therefore, we speculate that the activated partial thromboplastin time (APTT), an indicator of coagulation factor function, may be involved in the occurrence of CALs, but it has not been explored yet. This study aims to investigate the effect of the APTT level on CALs occurrence in the acute phase of KD.</div></div><div><h3>Methods</h3><div>A total of 2303 KD patients during a 10-year period were recruited at the Wenzhou Medical University affiliated Yuying Children's Hospital. A total of 1715 patients who completed the follow-up were enrolled in the final analysis and were divided into the low APTT group and the high APTT group at a 46 s cutoff before receiving intravenous immunoglobulin (IVIG) treatment. Multiple logistic regression analysis and stratified analysis were utilized to evaluate the independent impact of APTT levels on the occurrence of CALs and to determine the impact of APTT levels on the occurrence of CALs in different subgroups, respectively.</div></div><div><h3>Results</h3><div>The incidence of CALs in the low APTT group and the high APTT group was 12.5 % and 17.5 %, respectively (<em>P</em> = 0.005). Patients with high APTT levels had higher CRP levels (<em>P</em> < 0.001). High APTT levels were the independent risk factor on the occurrence of CALs; the adjusted odds ratio (OR) was 1.523 (95 % CI: 1.144, 2.028). Similar results were found in stratification analysis and sensitivity analysis.</div></div><div><h3>Conclusions</h3><div>KD patients with high APTT levels (≥46 s) before IVIG treatment may be more prone to developing CALs in the acute phase of KD.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104817"},"PeriodicalIF":2.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937928","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}
Pub Date : 2025-05-07DOI: 10.1016/j.mvr.2025.104816
Guanping Tan , Jing Wang , Wenli Xing , Zhaohui He
Large vessel spasm after aneurysmal subarachnoid hemorrhage (aSAH) does not fully explain the mechanism underlying delayed cerebral ischemia (DCI), and increasing evidence suggests that microcirculatory function plays an important role in DCI. Previous studies on PDGF-BB and its downstream pathways have focused mostly on large vessel spasms after SAH, and no attention has been given to the relationship between the PDGF pathway and microcirculation. By establishing in vitro and ex vivo mouse SAH models via the addition of PDGF-BB and PDGFRβ antagonists, the expression of PDGFRβ and its downstream proteins was examined to assess the effects of the intervention on neurological function scores, cerebral edema, and blood–brain barrier permeability in mice after aSAH and to observe the state of the cerebral cortex microvasculature in each group of mice after model establishment using transmission electron microscopy. PDGFRβ expression increased after SAH and activated the downstream ERK and AKT pathways, and the inhibitor imatinib inhibited this effect. Imatinib administration ameliorated neurological impairments, reduced brain edema and significantly inhibited blood–brain barrier disruption in mice after SAH. One week after SAH, we observed that imatinib intervention attenuated damage to the microcirculatory system and partially preserved the normal function of the microcirculation. Imatinib reduced BBB disruption and improved microcirculatory function in the early post-SAH period by blocking PDGFR and its downstream pathway, thereby attenuating neurological impairment after SAH. The PDGF-BB–PDGFR-β pathway may play an important role in post-SAH DCI.
{"title":"The role of the PDGF-BB/PDGFR-β signaling pathway in microcirculatory disturbances and BBB destruction after experimental subarachnoid hemorrhage in mice","authors":"Guanping Tan , Jing Wang , Wenli Xing , Zhaohui He","doi":"10.1016/j.mvr.2025.104816","DOIUrl":"10.1016/j.mvr.2025.104816","url":null,"abstract":"<div><div>Large vessel spasm after aneurysmal subarachnoid hemorrhage (aSAH) does not fully explain the mechanism underlying delayed cerebral ischemia (DCI), and increasing evidence suggests that microcirculatory function plays an important role in DCI. Previous studies on PDGF-BB and its downstream pathways have focused mostly on large vessel spasms after SAH, and no attention has been given to the relationship between the PDGF pathway and microcirculation. By establishing in vitro and ex vivo mouse SAH models via the addition of PDGF-BB and PDGFRβ antagonists, the expression of PDGFRβ and its downstream proteins was examined to assess the effects of the intervention on neurological function scores, cerebral edema, and blood–brain barrier permeability in mice after aSAH and to observe the state of the cerebral cortex microvasculature in each group of mice after model establishment using transmission electron microscopy. PDGFRβ expression increased after SAH and activated the downstream ERK and AKT pathways, and the inhibitor imatinib inhibited this effect. Imatinib administration ameliorated neurological impairments, reduced brain edema and significantly inhibited blood–brain barrier disruption in mice after SAH. One week after SAH, we observed that imatinib intervention attenuated damage to the microcirculatory system and partially preserved the normal function of the microcirculation. Imatinib reduced BBB disruption and improved microcirculatory function in the early post-SAH period by blocking PDGFR and its downstream pathway, thereby attenuating neurological impairment after SAH. The PDGF-BB–PDGFR-β pathway may play an important role in post-SAH DCI.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104816"},"PeriodicalIF":2.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921956","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}
Pub Date : 2025-05-03DOI: 10.1016/j.mvr.2025.104814
Clarissa Becher , Martin Frauenlob , Florian Selinger , Peter Ertl , Marie-José Goumans , Gonzalo Sanchez-Duffhues
The vascular endothelium is constantly subjected to hemodynamic forces, including tangential shear stress, which are crucial for maintaining vascular homeostasis. Pathological shear stress levels, such as those observed in pulmonary arterial hypertension (PAH) or atherosclerosis, disrupt this balance, driving vascular remodeling and endothelial dysfunction. Current microfluidic platforms for studying these conditions are limited by high costs, excessive reagent requirements, and non-physiological channel geometries. Here we introduce a novel microfluidic chip system, a Nylon Vessel-on-a-Chip (NVoC) which represents a cost-effective and straightforward fabrication platform that eliminates the need for specialized equipment and enables a physiologically relevant round channel geometry. The NVoC was fabricated using Polydimethylsiloxane (PDMS) and nylon threads, with surface activation achieved through polydopamine and collagen-I coating, enabling robust endothelial cell (EC) attachment and long-term culture. Immortalized endothelial colony-forming cells (iECFCs) and human umbilical vein EC (HUVECs) were used to optimize and validate the platform, demonstrating its compatibility with high shear stress conditions (up to 90 dyne/cm2) and various molecular biology techniques, including RT-qPCR, Western blotting, and immunofluorescent staining. With fabrication costs six times lower than commercial alternatives and overall experimental costs reduced threefold, the NVoC offers the ability to expose endothelial cells to physiological and pathological shear stress levels in a reproducible, accessible, and scalable manner. Its versatility and affordability make it a valuable tool for investigating shear stress-related mechanisms in microvascular diseases, particularly PAH, with potential applications in drug discovery and translational research.
血管内皮不断受到血流动力学力的影响，包括切向剪切应力，这对维持血管稳态至关重要。病理性剪切应力水平，如在肺动脉高压（PAH）或动脉粥样硬化中观察到的水平，破坏了这种平衡，驱动血管重塑和内皮功能障碍。目前用于研究这些条件的微流控平台受到高成本、过多试剂需求和非生理通道几何形状的限制。在这里，我们介绍了一种新的微流控芯片系统，尼龙容器芯片（NVoC），它代表了一种具有成本效益和直接的制造平台，消除了对专门设备的需求，并实现了生理相关的圆形通道几何形状。NVoC由聚二甲基硅氧烷（PDMS）和尼龙线制成，通过聚多巴胺和胶原- i涂层实现表面激活，使内皮细胞（EC）附着和长期培养稳定。利用永生化内皮细胞集落形成细胞（iecfc）和人脐静脉细胞集落形成细胞（HUVECs）对平台进行优化和验证，证明其与高剪切应力条件（高达90 dyne/cm2）和各种分子生物学技术（包括RT-qPCR， Western blotting和免疫荧光染色）的兼容性。NVoC的制造成本比商业替代品低6倍，总体实验成本降低了3倍，能够以可复制、可获取和可扩展的方式将内皮细胞暴露在生理和病理剪切应力水平下。它的多功能性和可负担性使其成为研究微血管疾病（特别是多环芳烃）中剪切应力相关机制的宝贵工具，在药物发现和转化研究中具有潜在的应用前景。
{"title":"A cost-effective vessel-on-a-chip for high shear stress applications in vascular biology","authors":"Clarissa Becher , Martin Frauenlob , Florian Selinger , Peter Ertl , Marie-José Goumans , Gonzalo Sanchez-Duffhues","doi":"10.1016/j.mvr.2025.104814","DOIUrl":"10.1016/j.mvr.2025.104814","url":null,"abstract":"<div><div>The vascular endothelium is constantly subjected to hemodynamic forces, including tangential shear stress, which are crucial for maintaining vascular homeostasis. Pathological shear stress levels, such as those observed in pulmonary arterial hypertension (PAH) or atherosclerosis, disrupt this balance, driving vascular remodeling and endothelial dysfunction. Current microfluidic platforms for studying these conditions are limited by high costs, excessive reagent requirements, and non-physiological channel geometries. Here we introduce a novel microfluidic chip system, a Nylon Vessel-on-a-Chip (NVoC) which represents a cost-effective and straightforward fabrication platform that eliminates the need for specialized equipment and enables a physiologically relevant round channel geometry. The NVoC was fabricated using Polydimethylsiloxane (PDMS) and nylon threads, with surface activation achieved through polydopamine and collagen-I coating, enabling robust endothelial cell (EC) attachment and long-term culture. Immortalized endothelial colony-forming cells (iECFCs) and human umbilical vein EC (HUVECs) were used to optimize and validate the platform, demonstrating its compatibility with high shear stress conditions (up to 90 dyne/cm<sup>2</sup>) and various molecular biology techniques, including RT-qPCR, Western blotting, and immunofluorescent staining. With fabrication costs six times lower than commercial alternatives and overall experimental costs reduced threefold, the NVoC offers the ability to expose endothelial cells to physiological and pathological shear stress levels in a reproducible, accessible, and scalable manner. Its versatility and affordability make it a valuable tool for investigating shear stress-related mechanisms in microvascular diseases, particularly PAH, with potential applications in drug discovery and translational research.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104814"},"PeriodicalIF":2.9,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937929","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}
Pub Date : 2025-04-30DOI: 10.1016/j.mvr.2025.104815
Jinfeng Cui , Liqing Luo , Hongmei Geng , Yunxiu Gao , Yuanyuan Chen , Qilin Yu , Xiao Huang , Xiaozhi Wang , Ting Sun
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 (P <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 (P < 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.
{"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}
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