Microvascular Research[JOURNAL]
Sun
200 papers
A theoretical model for oxygen transport to the cerebral cortex: effects of flow redistribution by penetrating arterioles.
Sharma A, Secomb TW
Microvasc Res · 2025 Sep · PMID 40581282 · Full text
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 simulat...
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 mm, 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.
Predictive value of the average three-vessel microvascular resistance in patients with non-ST-segment elevation myocardial infarction after percutaneous coronary intervention.
Hong R, Li B, Chen H … +6 more , Zhong J, Chen Y, Yan Y, Chen L, Chen Q, Luo Y
Microvasc Res · 2025 Sep · PMID 40581281 · Publisher ↗
OBJECTIVES: 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) afte...
OBJECTIVES: 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). METHODS: 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. RESULTS: 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 %，P = 0.001), higher QFR value (0.92 ± 0.05 vs. 0.88 ± 0.09, P < 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 < 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 %, P = 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, P < 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, P < 0.001). CONCLUSIONS: 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.
Nrf2 deficiency blunts exercise training-induced adaptations of coronary resistance arteries.
Park H, Medarev SL, Maraj JJ … +3 more , Restrepo A, Copp SW, Muller-Delp JM
Microvasc Res · 2025 Sep · PMID 40578507 · Publisher ↗
Exercise training upregulates nuclear factor erythroid 2-related factor 2 (Nrf2) expression and antioxidant production in various tissues; however, little is known about the role of Nrf2 in exercise training-induced adap...
Exercise training upregulates nuclear factor erythroid 2-related factor 2 (Nrf2) expression and antioxidant production in various tissues; however, little is known about the role of Nrf2 in exercise training-induced adaptations of blood vessels. This study investigated how deletion of Nrf2 affects vasomotor function in coronary resistance arteries in sedentary and exercise-trained rats. Wild-type (WT) and Nrf2 knockout (KO) rats underwent 10 weeks of treadmill exercise or remained sedentary. Coronary resistance arteries were isolated for assessment of vasomotor responses. In resistance arteries from Nrf2 KO rats, endothelin-induced constriction was blunted, but exercise training partially restored responsiveness to endothelin; after exercise training, responses to endothelin were not different between arteries from WT and Nrf2 KO rats. Similarly, KCl-induced constriction was reduced in arteries from Nrf2 KO rats, but exercise training reversed this loss of responsiveness to KCl. Nitric oxide (NO)-mediated vasodilation of coronary resistance arteries was not altered by deletion of Nrf2; however, exercise training enhanced NO-mediated dilation in arteries from WT, but not Nrf2 KO rats. Similarly, exercise training increased vasodilation to low concentrations of potassium (10 and 20 mM KCl) in arteries from WT, but not Nrf2 KO rats. These findings suggest that Nrf2 is critical to maintenance of contractile responses in coronary resistance arteries, but exercise training can restore contractile function through Nrf2-independent mechanisms. In contrast, vasodilatory responses to NO and low-level potassium are maintained in coronary resistance arteries from Nrf2-deficient rats, but exercise training fails to enhance these vasodilatory responses in the absence of Nrf2.
DDIT4 knockdown suppresses venous malformation progression by inhibiting NF-κB signaling as a potential therapeutic target.
He Y, Lin J, Li Y … +5 more , Cheng X, Wang T, Wang W, Zeng W, Li Y
Microvasc Res · 2025 Sep · PMID 40571189 · Publisher ↗
BACKGROUND: 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 ex...
BACKGROUND: 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. METHODS: Bioinformatic analysis identified DDIT4 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. RESULTS: 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. CONCLUSIONS: DDIT4 knockdown inhibits VMs progression by suppressing the NF-κB pathway, suggesting that DDIT4 may serve as a potential therapeutic target.
Three-dimensional choroidal changes in diabetes and diabetic retinopathy: An ultrawide-field swept-source optical coherence tomography angiography study.
Zheng Z, Hu L, Zhang Y … +4 more , Liu N, Gu X, Song S, Yu X
Microvasc Res · 2025 Sep · PMID 40545190 · Publisher ↗
PURPOSE: To investigate choroidal changes in different stages of diabetic retinopathy (DR), and determine the effect of panretinal photocoagulation (PRP) on choroid based on volumetric measurements of ultrawide-field swe...
PURPOSE: To investigate choroidal changes in different stages of diabetic retinopathy (DR), and determine the effect of panretinal photocoagulation (PRP) on choroid based on volumetric measurements of ultrawide-field swept-source optical coherence tomography angiography (UWF-SS-OCTA). METHODS: This observational study included 56 healthy controls, 192 treatment-naïve DR patients, and 42 PRP-treated DR patients who have undergone UWF-SS-OCTA measurements. Treatment-naïve DR patients were further grouped according to varying severity of DR. Choroidal parameters were analyzed and compared among these groups according to central and peripheral areas. Spearman analysis was performed to determine the association between non-perfusion area (NPA) and choroidal parameters. RESULTS: Compared with healthy controls, choroidal thickness (CT) and volume (CV), including both vascular and stromal volume (CVV/a and CSV/a) were decreased in treatment-naïve DR patients in full range, while choroidal vascularity index (CVI) decreased only in the peripheral area (P = 0.04). In detail, choroid was thinning in no-DR (NDR) and mild NPDR, followed by an increased trend in moderate and late stages of DR. NPA was positively associated with CT, CV, CVV/a, and CSV/a in moderate and late stages of DR. Choroidal parameters decreased in PRP-treated eyes except for an increase of CVI in the central area. CONCLUSION: Choroid was thinning in treatment-naïve DR eyes. Specifically, choroid decreased in the early stage and further increased with DR progression; increased expression of VEGF may be a key factor in choroidal thickening. PRP treatment could contribute to the redistribution of choroidal blood flow and improve the perfusion of the macula.
Time-course and pressure-dependent changes in microvascular responses during ischemic preconditioning.
Lubiak SM, Howard MA, Schmidt JT … +8 more , Patel NN, Prajapati AJ, Shah NM, Herring EK, Fukuda DH, Stout JR, Keller JL, Hill EC
Microvasc Res · 2025 Sep · PMID 40523499 · Publisher ↗
This investigation examined a moderate individualized pressure (i.e., percentage of total arterial occlusion pressure [TAOP]) compared to low and high absolute pressures on muscle tissue oxygenation (StO) throughout isch...
This investigation examined a moderate individualized pressure (i.e., percentage of total arterial occlusion pressure [TAOP]) compared to low and high absolute pressures on muscle tissue oxygenation (StO) throughout ischemic preconditioning (IPC). Fifteen males randomly completed three cycles of IPC at a low (20 mmHg [IPC]), moderate (80% of TAOP [IPC]), and high (220 mmHg [IPC]) pressure. Each cycle lasted 5 min at the assigned pressure, followed by 5 min of zero pressure on the dominant leg. StO was measured continuously and StO indices (i.e., downslope [StO], minimum [StO], upslope [StO], maximum [StO]) were analyzed with Bayesian models. StO and StO were pressure-dependent (IPC < IPC < IPC) as indicated by zero absent from all 95% high-density intervals (95% HDI) and 100% probability of an effect (Prob = 100%). During IPC, StO increased from cycle 1 to cycles 2 and 3 but plateaued from cycle 2 to 3 as indicated by zero absent from all 95% HDI's and Prob ≥87.6%. Additionally, StO was greater for IPC and IPC relative to IPC for cycles 1 and 2 but was pressure-dependent during cycle 3 as indicated by zero absent from all 95% HDI's and Prob = 98.8%. Lastly, StO was greater for IPC than IPC and IPC as indicated by zero absent from all 95% HDI's and Prob = 100%. Collectively, using moderate individualized pressure elicited similar StO as high absolute pressure, but only for cycles 1 and 2. These findings may be attributed to differences in the hypoxic-insult and/or vascular-related mechano-transduction stimuli.
Quantitative image analysis of nailfold capillaries during an in-hospital education program for type 2 diabetes or obesity.
Miyoshi K, Chikamori M, Ando T … +4 more , Nakata K, Aoyama T, Matsunaga YT, Yamauchi T
Microvasc Res · 2025 Sep · PMID 40490186 · Publisher ↗
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 capilla...
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.
Nailfold capillary morphology changes in patients with retinal vein occlusion.
Zhang W, Wu H, Zhang Y … +3 more , Gu X, Nie H, Wu Y
Microvasc Res · 2025 Jul · PMID 40447081 · Publisher ↗
AIM: 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, inclu...
AIM: 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.
Interfering with AQP1 alleviates ferroptosis, improves mitochondrial function and energy metabolic disorder in hypoxia/reoxygenation-induced H9c2 cardiomyocytes via Wnt/β-catenin pathway.
Xiang S, Tang X
Microvasc Res · 2025 Jul · PMID 40436134 · Publisher ↗
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 rep...
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(). 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.
Hyperglycemia-induced blood-brain barrier dysfunction: Mechanisms and therapeutic interventions.
Chen C, Xu X, Lu J … +3 more , Xiang Y, Shi L, Liu D
Microvasc Res · 2025 Jul · PMID 40393562 · Publisher ↗
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 preventi...
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.
Day-to-day variability in cutaneous microcirculation measured with multi-exposure laser speckle contrast imaging and multispectral imaging.
Nilsson M, Hultman M, Richter F … +5 more , Henricson J, Larsson M, Strömberg T, Fredriksson I, Iredahl F
Microvasc Res · 2025 Jul · PMID 40378918 · Publisher ↗
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 flow...
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.
MicroRNA regulatory dynamic, emerging diagnostic and therapeutic frontier in atherosclerosis.
Zaidi SA, Fan Z, Chauhdari T … +1 more , Ding Y
Microvasc Res · 2025 Jul · PMID 40368159 · Publisher ↗
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 dri...
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.
The role of the PDGF-BB/PDGFR-β signaling pathway in microcirculatory disturbances and BBB destruction after experimental subarachnoid hemorrhage in mice.
Tan G, Wang J, Xing W … +1 more , He Z
Microvasc Res · 2025 Jul · PMID 40345321 · Publisher ↗
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...
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.
Activated partial thromboplastin time levels and coronary artery lesions in Kawasaki disease: A retrospective cohort study.
Zhou J, Ni C, Wang Z … +9 more , Xia Y, Shi H, Zhao X, Chen Y, Liu C, Rong X, Wu R, Chu M, Qiu H
Microvasc Res · 2025 Jul · PMID 40345320 · Publisher ↗
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 respon...
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.
A cost-effective vessel-on-a-chip for high shear stress applications in vascular biology.
Becher C, Frauenlob M, Selinger F … +3 more , Ertl P, Goumans MJ, Sanchez-Duffhues G
Microvasc Res · 2025 Jul · PMID 40324629 · Publisher ↗
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...
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) 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.
Proteomics suggests the role of Cxcl12 secreted by hucMSCs in the treatment of lipopolysaccharide-acute lung injury.
Cui J, Luo L, Geng H … +6 more , Gao Y, Chen Y, Yu Q, Huang X, Wang X, Sun T
Microvasc Res · 2025 Jul · PMID 40311750 · Publisher ↗
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 (h...
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.
Effects of veno-arterial extracorporeal membrane oxygenation on skeletal muscle function and interstitial PO in contracting muscle of normal rats.
Hotta K, Fujii Y, Hitosugi N … +4 more , Takamizawa R, Inoue T, Tamiya H, Tsubaki A
Microvasc Res · 2025 Jul · PMID 40280480 · Publisher ↗
BACKGROUND: This study aimed to clarify the effects of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) on skeletal muscle oxygen pressure and function in rats. METHODS: Male Sprague-Dawley rats (2-3 months ol...
BACKGROUND: This study aimed to clarify the effects of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) on skeletal muscle oxygen pressure and function in rats. METHODS: Male Sprague-Dawley rats (2-3 months old, n = 17) were randomized into control and VA-ECMO groups. All animals were anesthetized and mechanically ventilated. The VA-ECMO circuit was established by cannulating the right jugular vein and left carotid artery. Interstitial PO in the tibialis anterior (TA) muscle was measured using a phosphorescence quenching technique during electrically induced muscle contractions. Muscle tension was analyzed to evaluate the rate of force development (RFD) and relaxation rate. RESULTS: Compared to controls, arterial oxygen pressure (PaO) was significantly higher, while hemoglobin levels were significantly lower in the VA-ECMO group (both p < 0.01). Interstitial PO was significantly reduced at rest and during contractions in the VA-ECMO group (both p < 0.01). Muscle relaxation was delayed, and peak tension was lower in the VA-ECMO group compared to controls (both p < 0.01). CONCLUSIONS: VA-ECMO impairs skeletal muscle function and reduces interstitial PO2 in contracting muscles, effects that appear independent of hyperoxemia. These findings provide insight into the microcirculatory and functional consequences of VA-ECMO on skeletal muscle.
The influence of cuff location on the oxygenation and reperfusion of the foot during ischemic preconditioning: A reliability study.
French C, Robbins D, Gernigon M … +1 more , Gordon D
Microvasc Res · 2025 Jul · PMID 40246226 · Publisher ↗
Ischemic preconditioning (IPC) involves the application of occlusion cycles, typically prior to exercise. IPC is commonly applied at the arm or thigh for improving exercise performance, which can be combined with near-in...
Ischemic preconditioning (IPC) involves the application of occlusion cycles, typically prior to exercise. IPC is commonly applied at the arm or thigh for improving exercise performance, which can be combined with near-infrared spectroscopy (NIRS) to assess the microcirculation and tissue oxygenation. Despite the use of NIRS during IPC, few studies have investigated the reliability of NIRS during lower limb IPC with no relevant publications investigating IPC at the ankle. Therefore, the purpose of this study was to investigate the intra-session reliability in the NIRS measurements during repeated IPC at the thigh, ankle and arm. Eighteen participants volunteered. IPC was applied at the thigh (220 mmHg), ankle (individualized arterial occlusion pressure: 212 ± 24 mmHg) and arm (220 mmHg) in a randomized order involving 3 repeated cycles of 5-min occlusion and reperfusion, within a session. NIRS recorded tissue oxygen saturation (SO), oxygenated (OHb) and deoxygenated hemoglobin (HHb) at the abductor hallucis muscle. Reliability was assessed using intraclass correlation coefficients. For all NIRS measurements assessed, there was excellent reliability (All ICC > 0.94) for the average, minimum and maximum values. The results indicate that IPC can successfully be applied at the ankle, offering reliable measures between three repeated occlusions within a session.
Glial and blood-brain barrier cell-derived exosomes: Implications in stroke.
Mathias K, Machado RS, Petronilho T … +4 more , Sulzbacher VAR, de Rezende VL, Prophiro JS, Petronilho F
Microvasc Res · 2025 Jul · PMID 40246225 · Publisher ↗
Exosomes are small extracellular vesicles released by cells that play a pivotal role in intercellular communication, significantly influencing both the pathophysiology and potential treatment of ischemic stroke (IS). Thi...
Exosomes are small extracellular vesicles released by cells that play a pivotal role in intercellular communication, significantly influencing both the pathophysiology and potential treatment of ischemic stroke (IS). This review examines exosomes derived from key brain cell types, including microglia, astrocytes, oligodendrocytes, oligodendrocyte precursor cells (NG2+ cells), endothelial cells, and pericytes, emphasizing their molecular cargo and functional impact in IS. Microglia-derived exosomes regulate neuroinflammation, with M2-type exosomes exhibiting neuroprotective effects, while astrocyte-derived exosomes modulate pathways involved in pyroptosis and autophagy, influencing neuronal survival. Oligodendrocyte and NG2+ cell-derived exosomes contribute to remyelination, axonal growth, and inflammatory modulation. Endothelial and pericyte-derived exosomes play critical roles in BBB integrity, neurovascular remodeling, and drug transport across the BBB. This synthesis highlights recent advances in understanding how exosome-mediated communication impacts IS recovery and explores their translational potential for biomarker development and targeted therapies. By manipulating exosomal composition and delivery mechanisms, novel therapeutic strategies may emerge, offering hope for improved IS treatment outcomes.
Localized pulmonary vascular changes in a mouse model of subarachnoid hemorrhage created by combining filament perforation and blood injection.
Tochinai R, Suzuki T, Tomita K … +5 more , Sekizawa SI, Okada Y, Taki Y, Kuwahara M, Mutoh T
Microvasc Res · 2025 Jul · PMID 40233848 · Publisher ↗
INTRODUCTION: Subarachnoid hemorrhage (SAH) results in neurogenic pulmonary edema (NPE), a condition with a high mortality rate arising from increased hydrostatic pressure and vascular permeability. Two possible mechanis...
INTRODUCTION: Subarachnoid hemorrhage (SAH) results in neurogenic pulmonary edema (NPE), a condition with a high mortality rate arising from increased hydrostatic pressure and vascular permeability. Two possible mechanisms of NPE are increased hydrostatic pressure and increased vascular permeability, and it is possible that increased permeability of capillaries in the lungs may contribute to the exacerbation of NPE. Recent research has highlighted the importance of the glycocalyx, a gel-like layer that lines blood vessels, in regulating vascular permeability in various diseases. However, its role in NPE after SAH has not been previously explored. This study investigated the involvement of the glycocalyx in the development of NPE by developing a mouse model of SAH. METHODS: The SAH model was developed by combining internal carotid artery (ICA) perforation and blood infusion into the cisterna magna of mice. The histological structure of the lungs was confirmed using micro-CT, histopathological examination, and scanning electron microscopy. RESULTS: Despite no obvious micro-CT findings indicating pulmonary edema, histopathological changes in hematoxylin and eosin-stained lung were detected. Scanning electron microscopy revealed glycocalyx exfoliation within the pulmonary microvascular wall. A trend toward higher plasma syndecan-1 levels was also observed. CONCLUSION: The combination of ICA perforation and blood infusion into the cisterna magna can produce pulmonary findings in mice that mimic NPE after SAH. The results also suggest that glycocalyx loss is involved in the development of NPE after SAH.
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