Microvascular research最新文献_第7页

Nrf2 deficiency blunts exercise training-induced adaptations of coronary resistance arteries Nrf2缺乏使运动训练诱导的冠状动脉阻力适应变迟钝。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-06-25 DOI: 10.1016/j.mvr.2025.104837

Hyerim Park , Steven L. Medarev , Joshua J. Maraj , Alexis Restrepo , Steven W. Copp , Judy M. Muller-Delp

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.

运动训练上调核因子红细胞2相关因子2 （Nrf2）的表达和各组织抗氧化剂的产生；然而，Nrf2在运动训练诱导的血管适应性中的作用知之甚少。本研究探讨了Nrf2缺失如何影响久坐和运动训练大鼠冠状动脉血管舒缩功能。野生型（WT）和Nrf2敲除（KO）大鼠进行10 周的跑步机运动或保持久坐。分离冠脉阻力动脉以评估血管舒缩反应。在Nrf2 KO大鼠的阻力动脉中，内皮素诱导的收缩被减弱，但运动训练部分恢复了对内皮素的反应性；运动训练后，WT和Nrf2 KO大鼠动脉对内皮素的反应没有差异。同样，Nrf2 KO大鼠的动脉中KCl诱导的收缩减少，但运动训练逆转了这种对KCl的反应性丧失。一氧化氮（NO）介导的冠状动脉血管舒张不因Nrf2的缺失而改变；然而，运动训练增强了WT大鼠no介导的动脉扩张，而Nrf2 KO大鼠则没有。同样，运动训练增加了WT大鼠动脉中低浓度钾（10和20 mM KCl）的血管舒张，但Nrf2 KO大鼠没有。这些发现表明Nrf2对于维持冠状动脉的收缩反应至关重要，但运动训练可以通过Nrf2独立的机制恢复收缩功能。相比之下，Nrf2缺乏的大鼠冠状动脉对NO和低水平钾的血管舒张反应得以维持，但在缺乏Nrf2的情况下，运动训练不能增强这些血管舒张反应。

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引用次数: 0

DDIT4 knockdown suppresses venous malformation progression by inhibiting NF-κB signaling as a potential therapeutic target dddit4敲低通过抑制NF-κB信号传导抑制静脉畸形进展作为潜在的治疗靶点。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-06-24 DOI: 10.1016/j.mvr.2025.104833

Yang He , Jian Lin , Yi Li , Xiaobo Cheng , Tong Wang , Wei Wang , Weixing Zeng , Yongsheng Li

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.

背景：本研究旨在探讨DNA损伤诱导转录本4 （DNA Damage Inducible Transcript 4, DDIT4）在静脉畸形（Venous Malformations, vm）发病中的调控作用及其分子机制，为潜在的靶向治疗提供基础实验依据。方法：通过生物信息学分析，确定dddit4是vm中关键的差异表达基因，并采用sgGSEA方法预测其潜在的生物学功能。采用免疫组织化学染色和免疫荧光法验证DDIT4的表达水平及其与血管密度的关系。建立慢病毒vm细胞模型，评估dddit4表达水平。我们评估了DDIT4敲低对vm细胞功能的影响，并通过转录组测序和Western blot分析获得了机制见解。使用3D vm细胞模型和敲除DDIT4的裸鼠异种移植进一步验证。此外，在DDIT4敲除的vm三维细胞模型和裸鼠异种移植中，通过脂多糖（LPS）激活NF-κB通路进行外源性功能拯救实验，进一步研究DDIT4的作用。结果：dddit4在vm组织中表达上调，与血管生成相关。DDIT4敲低增加细胞圆度，抑制增殖、迁移和NF-κB通路激活，阻断vm 3D模型血管生成和裸鼠异种移植瘤病变形成，同时抑制二者的NF-κB通路。NF-κB通路激活可恢复两种模型的血管生成。结论：DDIT4敲低可通过抑制NF-κB通路抑制vm进展，提示DDIT4可能是一个潜在的治疗靶点。

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引用次数: 0

Three-dimensional choroidal changes in diabetes and diabetic retinopathy: An ultrawide-field swept-source optical coherence tomography angiography study 糖尿病和糖尿病视网膜病变的三维脉络膜改变：一项超宽视场扫描源光学相干断层血管造影研究

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-06-20 DOI: 10.1016/j.mvr.2025.104832

Zhaoxia Zheng , Lei Hu , Yue Zhang , Nianen Liu , Xiaoya Gu , Shuang Song , Xiaobing Yu

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.

目的探讨糖尿病视网膜病变（DR）不同阶段脉络膜的变化，并通过超宽视场扫描源光学相干断层血管造影（UWF-SS-OCTA）的体积测量来确定全视网膜光凝（PRP）对脉络膜的影响。方法本观察性研究包括56名健康对照、192名treatment-naïve DR患者和42名接受prp治疗的DR患者，这些患者接受了UWF-SS-OCTA测量。Treatment-naïve将DR患者根据DR的严重程度进行分组，并根据中心区和外周区对各组脉络膜参数进行分析和比较。采用Spearman分析确定非灌注面积（NPA）与脉络膜参数之间的关系。结果与健康对照组相比，treatment-naïve DR患者脉络膜厚度（CT）和体积（CV），包括血管和间质体积（CVV/a和CSV/a）均全面降低，脉络膜血管指数（CVI）仅在外周区降低（P = 0.04）。在无dr （NDR）和轻度NPDR中脉络膜变薄，随后在dr中晚期呈增加趋势。NPA与dr中晚期CT、CV、CVV/a和CSV/a呈正相关，prp治疗的眼睛脉络膜参数下降，但中心区域CVI增加。结论treatment-naïve DR眼脉络膜变薄。具体来说，脉络膜在早期减少，随着DR的进展进一步增加；VEGF表达增加可能是脉络膜增厚的关键因素。PRP治疗有助于脉络膜血流的重新分布，改善黄斑的血流灌注。

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引用次数: 0

Time-course and pressure-dependent changes in microvascular responses during ischemic preconditioning 缺血预处理期间微血管反应的时间过程和压力依赖性变化。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-06-14 DOI: 10.1016/j.mvr.2025.104831

Sean M. Lubiak , Mason A. Howard , Jeffrey T. Schmidt , Nihar N. Patel , Anuj J. Prajapati , Niriham M. Shah , Emma K. Herring , David H. Fukuda , Jeffrey R. Stout , Joshua L. Keller , Ethan C. Hill

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 (StO₂) throughout ischemic preconditioning (IPC). Fifteen males randomly completed three cycles of IPC at a low (20 mmHg [IPC_SHAM]), moderate (80% of TAOP [IPC_80%]), and high (220 mmHg [IPC_220mmHg]) pressure. Each cycle lasted 5 min at the assigned pressure, followed by 5 min of zero pressure on the dominant leg. StO₂ was measured continuously and StO₂ indices (i.e., downslope [StO_2down], minimum [StO_2min], upslope [StO_2up], maximum [StO_2max]) were analyzed with Bayesian models. StO_2down and StO_2min were pressure-dependent (IPC_SHAM < IPC_80% < IPC_220mmHg) as indicated by zero absent from all 95% high-density intervals (95% HDI) and 100% probability of an effect (Prob = 100%). During IPC_220mmHg, StO_2up 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_2up was greater for IPC_80% and IPC_220mmHg relative to IPC_SHAM 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_2max was greater for IPC_220mmHg than IPC_SHAM and IPC_80% as indicated by zero absent from all 95% HDI's and Prob = 100%. Collectively, using moderate individualized pressure elicited similar StO_2up 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.

本研究检查了在缺血预处理（IPC）过程中，与肌肉组织氧合（StO2）的低和高绝对压力相比，适度的个体化压力（即动脉闭塞压[TAOP]的百分比）。15名男性随机在低（20 mm Hg [IPCSHAM]）、中（80 % TAOP [IPC80%]）和高（220 mm Hg [IPC220mmHg]）压力下完成3个IPC周期。在指定压力下，每个循环持续5 min，然后在优势腿上进行5 min的零压力。连续测量StO2，用贝叶斯模型分析StO2指数（即下坡[StO2down]、最小[StO2min]、上坡[StO2up]、最大值[StO2max]）。StO2down和StO2min是压力依赖性的（IPCSHAM 80% 220mmHg），由所有95 %高密度区间（95 % HDI）的零缺失和100 %影响概率（Prob = 100 %）表示。在IPC220mmHg期间，StO2up从循环1到循环2和3增加，但从循环2到3趋于平稳，所有95 % HDI和Prob≥87.6% %均为零。此外，在循环1和2中，相对于IPCSHAM， IPC80%和IPC220mmHg的StO2up更大，但在循环3中，所有95 % HDI和Prob = 98.8 %中都不存在零，这表明StO2up在压力依赖性。最后，IPC220mmHg的StO2max大于IPCSHAM和IPC80%，所有95个 % HDI和Prob中均为零， = 100 %。总的来说，使用适度的个例压力会引起与高绝对压力相似的StO2up，但仅适用于循环1和2。这些发现可能归因于缺氧损伤和/或血管相关的机械传导刺激的差异。

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引用次数: 0

Quantitative image analysis of nailfold capillaries during an in-hospital education program for type 2 diabetes or obesity 2型糖尿病或肥胖症住院教育项目中甲襞毛细血管的定量图像分析

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-06-07 DOI: 10.1016/j.mvr.2025.104830

Kengo Miyoshi , Masatomo Chikamori , Takashi Ando , Kengo Nakata , Tomohisa Aoyama , Yukiko T. Matsunaga , Toshimasa Yamauchi

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.

甲襞毛细血管是位于指甲近端皮肤下的小u形血管，其形态会因各种疾病而改变。本研究利用显微镜定量分析了住院2周接受教育和治疗的2型糖尿病（T2D）或肥胖患者的甲襞毛细血管。我们的结果表明甲襞动脉直径和吸烟史是糖尿病神经病变的有用预测因子。住院期间尿白蛋白/肌酐比值升高与静脉直径减小相关，反映了糖尿病肾病患者潜在的血管内低白蛋白血症。体重指数和住院期间的短期体重减轻与毛细血管和血管周围区之间的颜色对比相关，定义为delta E。这些结果表明，T2D和肥胖患者的甲襞毛细血管形态可能是糖尿病神经病变和肾病的有用指标，而delta E是这些人群细胞外水量的有用指标。这是第一个观察与生活方式相关疾病干预有关的甲襞毛细血管形态短期变化的研究。

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引用次数: 0

Nailfold capillary morphology changes in patients with retinal vein occlusion 视网膜静脉闭塞患者甲襞毛细血管形态的改变

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-05-28 DOI: 10.1016/j.mvr.2025.104822

Wenbo Zhang, Hailong Wu, Yadi Zhang, Xiaopeng Gu, Hongping Nie, Yuan Wu

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.

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。

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引用次数: 0

Interfering with AQP1 alleviates ferroptosis, improves mitochondrial function and energy metabolic disorder in hypoxia/reoxygenation-induced H9c2 cardiomyocytes via Wnt/β-catenin pathway 干扰AQP1可通过Wnt/β-catenin途径缓解缺氧/再氧诱导的H9c2心肌细胞的铁下垂，改善线粒体功能和能量代谢紊乱。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-05-26 DOI: 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.

心肌缺血再灌注（I/R）损伤是冠状动脉疾病的主要病理表现，与心血管不良结局密切相关。水通道蛋白1 （Aquaporin 1, AQP1）是一种在心肌I/R损伤过程中高表达的水分子。本研究旨在探讨AQP1在心肌I/R损伤中的作用及其作用机制。采用RT-qPCR和western blotting检测AQP1的表达。CCK-8法检测细胞活力。采用JC-1染色法、MitoSox-Red染色法和ATP- red 1探针分别检测线粒体膜电位、线粒体ROS （mtROS）和ATP合成。C11-BODIPY 581/591探针和FerroOrange探针分别测定脂质活性氧（ROS）和铁（2+）。采用Seahorse XFe96分析仪检测耗氧量（OCR）。检测试剂盒用于估计线粒体通透性过渡孔（mPTP）开度、总铁和脂质过氧化水平。Western blotting检测铁下垂、能量代谢和Wnt/β-catenin通路相关蛋白的表达。缺氧/再氧化（H/R）暴露的H9c2细胞AQP1表达升高。AQP1缺失可提高H/ r损伤H9c2细胞的活力，改善线粒体功能障碍、铁下垂和能量代谢紊乱。此外，AQP1缺失可能激活Wnt/β-catenin通路，而Wnt信号通路抑制剂XAV939可以部分恢复AQP1敲低对H/ r处理的H9c2细胞活力、线粒体功能、铁凋亡和能量代谢的影响。综上所述，AQP1干扰可能通过调节Wnt/β-catenin通路，对H/ r诱导的H9c2细胞线粒体功能障碍、铁凋亡和能量代谢紊乱起到保护作用。

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引用次数: 0

Hyperglycemia-induced blood-brain barrier dysfunction: Mechanisms and therapeutic interventions 高血糖诱导的血脑屏障功能障碍：机制和治疗干预

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-05-18 DOI: 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.

血脑屏障（BBB）作为一个高度选择性的界面，调节血液和大脑之间的分子运输。其完整性对于维持神经元稳态和预防神经炎症至关重要。高血糖症是糖尿病的一个标志，它与认知缺陷和中枢神经系统（CNS）病理（包括血管性痴呆、中风和阿尔茨海默病）有关，血脑屏障损伤是一个潜在的促成因素。随着全球糖尿病患病率的上升，了解高血糖和血脑屏障功能障碍之间的联系可能有助于开发保护或恢复血脑屏障完整性的新疗法，从而减轻糖尿病的神经系统并发症。此外，它可能有助于开发针对糖尿病相关神经系统并发症的靶向治疗方法。这篇文献综述探讨了高血糖和血脑屏障功能障碍之间关系的新见解。它侧重于血脑屏障功能障碍的机制，这种功能障碍在糖尿病和脑血管疾病中的临床表现，以及潜在的治疗干预措施。

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引用次数: 0

Day-to-day variability in cutaneous microcirculation measured with multi-exposure laser speckle contrast imaging and multispectral imaging 用多曝光激光散斑对比成像和多光谱成像测量皮肤微循环的日常变化。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-05-14 DOI: 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.

微循环功能障碍与心血管危险因素、慢性疾病（如糖尿病）和急性疾病（如感染性休克）有关。非侵入性光学技术激光多普勒血流法（LDF）和漫反射光谱法（DRS）通常用于测量灌注和氧饱和度，但仅限于单点测量，使其对空间变化敏感。多曝光激光散斑对比成像（MELSCI）和多光谱成像（MSI）通过在更大的皮肤区域捕获参数，克服了这一限制。目的：评估动脉闭塞释放后前臂和足底足在基线和峰值反应时的速度分解灌注和氧饱和度的日常变异性，同时评估性别和年龄的影响。方法：采用MELSCI和MSI对48名参与者（20-30岁男性12名，女性12名，50-60岁男性12名，女性12名）在一周内进行两次测量。每次测量持续60 min，在基线（10 min）、闭塞期间（5 min）和闭塞后（5 min）测量灌注和氧饱和度，作为整个成像组织区域的空间平均值。结果：年龄越大，足部灌注峰值越高（p = 0.006）。变异（CV）范围为1.4 %至19 %，足部低速灌注在峰值时显示出性别和年龄相关的差异（p = 0.007）。结论：年龄和性别影响微循环参数，与既往研究一致。MELSCI和MSI表现出较低的日常变异性，使它们成为临床疾病监测的有希望的技术。MELSCI灌注的可变性低于先前报道的激光散斑造影（LSCI）灌注。

{"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}

引用次数: 0

MicroRNA regulatory dynamic, emerging diagnostic and therapeutic frontier in atherosclerosis MicroRNA调控动态，动脉粥样硬化新诊断和治疗前沿

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-05-12 DOI: 10.1016/j.mvr.2025.104818

Syeda Armana Zaidi, Zhiyu Fan, Talha Chauhdari, Yongsheng Ding

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.

MicroRNAs （miRNAs）是一类非编码rna，是基因表达的关键转录后调控因子，在动脉粥样硬化（AS）的发病机制中具有重要意义。作为一种由血管细胞功能障碍、脂质失调和随后的慢性炎症驱动的进行性动脉疾病，As仍然是全球发病率的主要原因。最近的研究已经证明了mirna在调节血管壁的中枢生物过程中是多么重要，如内皮功能、血管平滑肌细胞（VSMC）表型转换和巨噬细胞极化。这篇综述根据mirna对内皮细胞、巨噬细胞和VSMCs的影响，对其在动脉粥样硬化斑块的发展和复杂性中的作用提供了全面的见解。我们还讨论了mirna作为治疗靶点和诊断生物标志物的发展前景，为血管疾病的研究提供了信息。最后，我们讨论了最近的并发症和基于mirna的方法在临床实践中的潜在应用。

引用次数: 0