Microvascular research最新文献_第6页

Acute effects of belt electrode-skeletal muscle electrical stimulation on microvascular responsiveness of the gastrocnemius muscle in healthy young men 带电极-骨骼肌电刺激对健康青年腓肠肌微血管反应性的急性影响

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-07-08 DOI: 10.1016/j.mvr.2025.104840

Hajime Tamiya , Hina Kawashiri , Toshiaki Miyamoto , Yuko Kurosawa , Takafumi Hamaoka , Atsuhiro Tsubaki

Purpose

Belt electrode-skeletal muscle electrical stimulation (B-SES) improves muscle strength, mass, and exercise tolerance. However, its effects on skeletal muscle microvascular responsiveness remain unclear. In this study, we investigated the acute effects of a single B-SES session on gastrocnemius microvascular responsiveness in healthy young men.

Methods

In this randomized crossover study, 12 healthy young men (mean age: 20.8 ± 1.0 years) underwent two 20-min conditions: electrical stimulation at the sensory threshold (Sham, n = 12) and at the maximum intensity not causing discomfort (B-SES, n = 12). Gastrocnemius metabolic rate (tissue oxygen saturation [StO₂] downslope) and microvascular reperfusion rate (StO₂ upslope) were assessed using near-infrared spectroscopy and a vascular occlusion test.

Results

In the B-SES condition, the StO₂ downslope significantly steepened (Pre: −0.15 ± 0.03 %·s⁻¹, Post: −0.20 ± 0.03 %·s⁻¹, p = 0.002). The StO₂ upslope also significantly steepened (Pre: 1.58 ± 0.52 %·s⁻¹, Post: 2.56 ± 0.71 %·s⁻¹, p < 0.001). A significant negative correlation was observed between the StO₂ downslope and StO₂ upslope (r = −0.581, p = 0.047). No significant changes were observed in the Sham condition.

Conclusions

A single B-SES session applied to the lower extremity significantly increased gastrocnemius metabolic rate and was associated with enhanced microvascular reperfusion. These findings suggest B-SES may be a useful therapeutic approach to improving microvascular responsiveness, particularly in individuals with limited exercise capacity.

目的：带状电极-骨骼肌电刺激（B-SES）可以提高肌肉力量、质量和运动耐受性。然而，其对骨骼肌微血管反应性的影响尚不清楚。在这项研究中，我们调查了单次B-SES对健康年轻男性腓肠肌微血管反应性的急性影响。方法在这项随机交叉研究中，12名健康年轻男性（平均年龄：20.8±1.0岁）接受了两种20分钟的条件：感觉阈值电刺激（Sham, n = 12）和不引起不适的最大强度电刺激（B-SES, n = 12）。采用近红外光谱和血管闭塞试验评估腓肠肌代谢率（组织氧饱和度[StO2]下坡）和微血管再灌注率（StO2上坡）。结果在B-SES条件下，StO2下坡明显变陡（Pre:−0.15±0.03%·s−1,Post:−0.20±0.03%·s−1,p = 0.002）。StO2上坡也显著变陡(Pre: 1.58±0.52%·s−1,Post: 2.56±0.71%·s−1,p <；0.001)。StO2下坡与StO2上坡呈显著负相关（r = - 0.581, p = 0.047）。假手术组未见明显变化。结论下肢单次B-SES治疗可显著提高腓肠肌代谢率，微血管再灌注增强。这些发现表明，B-SES可能是改善微血管反应性的有效治疗方法，特别是对于运动能力有限的个体。

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引用次数: 0

Letter to the editor: “Pitfalls in the assessment of microcirculation” 给编辑的信：“评估微循环的陷阱”

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-07-07 DOI: 10.1016/j.mvr.2025.104841

Arnaldo Dubin

引用次数: 0

Kinetics of thromboxane A2 receptor-driven vascular tone in the cerebral cortex ex vivo 体外大脑皮层血栓素A2受体驱动的血管张力动力学

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-07-02 DOI: 10.1016/j.mvr.2025.104835

Simone Woodruff , Benjamin Zimmerman , Kevin J. Elk , Jennifer E. Jenks , Danica Bojovic , Anusha Mishra

Ex vivo imaging in acute cortical brain slices is a valuable tool to assess neurovascular coupling and is particularly useful for studying active, local changes in microvascular compartments in isolation from upstream or downstream changes in flow. However, the lack of vascular perfusion pressure ex vivo results in loss of vascular tone, which must be restored prior to experiments to unmask dilatory signals. The thromboxane A2 receptor agonist U46619 is a widely used preconstrictor, yet its dose-response properties and kinetics of action on different vascular segments are not fully known. Here, we characterize the effects of U46619 on cortical arterioles and capillaries in ex vivo slices from rats and mice. Dose response curves tested in acute rat brain slices using 0 to 1000 nM U46619 showed that maximal constriction is reached at ∼300 nM in both arterioles and capillaries. Extended application of 200 nM U46619 (∼66 % maximal dose) over 2 h revealed that, on average, capillaries constrict faster than arterioles in rat brain slices. Cross-species examination in mouse tissue showed that vessels in mouse brain slices respond faster and constrict stronger on average than in rat brain slices, and that mouse capillaries also constrict faster than mouse arterioles. Our observations suggest that near-maximal preconstriction can be achieved in ex vivo experiments using 200–300 nM U46619, with a minimum incubation time of 20 min for studies involving capillaries and at least 30 min for studies involving arterioles.

急性脑皮质切片的离体成像是评估神经血管耦合的一种有价值的工具，尤其适用于研究微血管室的局部活动变化，而不受上游或下游血流变化的影响。然而，体外血管灌注压力的缺乏导致血管张力的丧失，必须在实验之前恢复血管张力以揭示扩张信号。血栓素A2受体激动剂U46619是一种广泛使用的预收缩剂，但其剂量反应特性和作用于不同血管段的动力学尚不完全清楚。在这里，我们描述了U46619对大鼠和小鼠离体切片皮质小动脉和毛细血管的影响。使用0 ~ 1000 nM U46619在急性大鼠脑切片中测试的剂量反应曲线显示，在~ 300 nM时，小动脉和毛细血管均达到最大收缩。延长应用200 nM U46619（最大剂量的66%）超过2小时显示，平均而言，大鼠脑切片中的毛细血管收缩速度快于小动脉。在小鼠组织中进行的跨物种检查表明，小鼠脑切片中的血管平均比大鼠脑切片反应更快，收缩更强，小鼠毛细血管收缩也比小鼠小动脉收缩更快。我们的观察表明，在离体实验中，使用200-300 nM的U46619可以实现接近最大的预收缩，涉及毛细血管的研究至少需要20分钟的孵育时间，涉及小动脉的研究至少需要30分钟。

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引用次数: 0

Influence of isometric RPE-clamp exercise on fatigability, muscle oxygenation dynamics, and microvascular function in healthy young adults 等长rpe夹持运动对健康年轻人疲劳、肌肉氧合动力学和微血管功能的影响

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-07-02 DOI: 10.1016/j.mvr.2025.104839

Minyoung Kwak , Brian Benitez , Clara J. Mitchinson , Erik R. Snell , Haley C. Bergstrom

Purpose

This study investigated fatigability, reflected by torque responses and time to task failure (TTF), and time course of muscle oxygenation (SmO₂) dynamics, as well as microvascular function assessed by near-infrared spectroscopy-vascular occlusion test (NIRS-VOT), in response to low-intensity, isometric forearm flexion anchored to a constant rating of perceived exertion (RPE) level of 3 (0–10 scale).

Methods

Twenty-five healthy young adults (22.9 ± 4.8 yr) completed a pre-exercise VOT, maximal voluntary isometric contraction (MVIC), and RPE-clamp exercise (RPE = 3), followed by post-exercise MVIC and VOT. Initial torque, TTF, and SmO₂ dynamics were recorded during the RPE-clamp exercise. The time course of SmO₂ was analyzed in 5 % TTF segments. During the VOTs, slope 1 (desaturation rate), minimum SmO₂, slope 2 (reperfusion rate), maximum SmO₂, and area under the curve (AUC) were recorded.

Results

MVIC torque significantly decreased from pre- to post-exercise (−13.9 % ± 14.0 %; p < 0.001). Initial torque was 23.3 ± 10.3 % MVIC, and TTF was 436.3 ± 252.0 s. SmO₂ declined significantly from 0 % to 5 % TTF (p = 0.005), but returned to the initial value and remained stable across subsequent time intervals. Compared to pre-VOT, post-VOT exhibited significantly lower slope 1 (p < 0.001) and minimum SmO₂ (p = 0.002), and greater maximum SmO₂ (p = 0.013), while slope 2 (p = 0.065) and AUC (p = 0.379) were unchanged.

Conclusions

During the RPE-clamp exercise, the voluntary reduction in torque to maintain the assigned RPE likely resulted in stable muscle oxygen availability, preventing the development of hypoxic stimulus needed to enhance microvascular responsiveness. However, the low-intensity isometric RPE-clamp exercise combined with a post-VOT may enhance muscle aerobic metabolism through sustained oxygen utilization.

目的本研究通过扭矩反应和任务失败时间（TTF）、肌肉氧合（SmO2）动力学的时间过程以及近红外光谱血管闭塞试验（NIRS-VOT）评估的微血管功能来研究低强度、等距前臂屈曲对感知用力（RPE）固定等级为3（0-10量表）的反应。方法25例健康青年（22.9±4.8岁）完成运动前VOT、最大自主等距收缩（MVIC）和RPE夹持运动（RPE = 3），然后进行运动后MVIC和VOT。在rpe夹钳运动期间记录初始扭矩、TTF和SmO2动态。在5% TTF段中分析了SmO2的时间过程。在VOTs期间，记录斜率1（去饱和率）、最小SmO2、斜率2（再灌注率）、最大SmO2和曲线下面积（AUC）。结果运动前后smvic转矩显著降低(- 13.9%±14.0%；p & lt;0.001)。初始扭矩为23.3±10.3% MVIC， TTF为436.3±252.0 s。SmO2从0% TTF显著下降到5% TTF (p = 0.005)，但在随后的时间间隔内恢复到初始值并保持稳定。与vot前相比，vot后的斜率显著降低(p <；0.001)和最小SmO2 (p = 0.002)，最大SmO2 （p = 0.013）较大，而斜率2 （p = 0.065）和AUC （p = 0.379）不变。结论：在RPE钳夹运动中，自愿减少扭矩以维持指定的RPE可能会导致稳定的肌肉氧气供应，阻止了增强微血管反应性所需的缺氧刺激的发展。然而，低强度等长rpe夹紧运动结合vot后可能通过持续的氧利用来增强肌肉有氧代谢。

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引用次数: 0

Structural and causal links between retinal vascular geometry and neural layer thickness 视网膜血管几何形状和神经层厚度之间的结构和因果关系

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-06-27 DOI: 10.1016/j.mvr.2025.104834

Mayinuer Yusufu , Robert N. Weinreb , Mengtian Kang , Algis J. Vingrys , Xianwen Shang , Lei Zhang , Danli Shi , Mingguang He

Purpose

To investigate structural relationships between retinal vasculometry from color fundus photography (CFP) and neural layers obtained from Optical Coherence Tomography (OCT) scans.

Methods

This cross-sectional study used the Retina-based Microvascular Health Assessment System (RMHAS) to extract retinal vascular measurements in the 6*6 mm area centered on the macular region and analyzed their associations with OCT parameters. We investigated both pairwise correlations between individual retinal layers and vascular parameters and associations between sets of variables. Mendelian randomization was employed to investigate potential causality.

Results

Data from 67,918 eyes of 43,029 participants were included. Among neural layers, Ganglion Cell-Inner Plexiform Layer (GC-IPL) showed the most notable correlations with vascular Density and Complexity (r = 0.199 for arterial Vessel Area Density and r = 0.175 for Number of Segments). Inner Nuclear Layer (INL) thickness correlated with Width (r = 0.122) and arterial Vessel Area Density (r = 0.127). Mendelian randomization indicated a bidirectional causal relationship. Genetically predicted higher Vessel Density was associated with increased thickness across various retinal layers, with standardized effect size of 1.50 on Inner Segment/Outer Segment + Photoreceptor Segment thickness. Genetically predicted increases in retinal layer thicknesses, particularly the Outer Plexiform Layer, were linked to higher Vessel Density (standardized effect size 0.45) and Fractal Dimension (standardized effect size 0.48).

Conclusions

GC-IPL and INL were positively associated with vascular Density and Caliber. Multidimensional relationships indicate a complementary nature between retinal vascular and neural parameters, highlighting their value as a composite biomarker. Mendelian Randomization uncovered a bidirectional causal relationship, providing insights into novel therapeutic approaches targeting vascular and neuronal components.

目的探讨彩色眼底摄影（CFP）视网膜血管测量与光学相干断层扫描（OCT）神经层之间的结构关系。方法采用基于视网膜的微血管健康评估系统（RMHAS）提取黄斑中心6*6 mm区域视网膜血管测量值，分析其与OCT参数的相关性。我们调查了个体视网膜层和血管参数之间的两两相关性以及变量集之间的关联。采用孟德尔随机化来调查潜在的因果关系。结果纳入了43029名参与者的67918只眼睛的数据。在神经层中，神经节细胞-内丛状层（GC-IPL）与血管密度和复杂性的相关性最显著（动脉血管面积密度r = 0.199，节段数r = 0.175）。内核层（INL）厚度与宽度（r = 0.122）和动脉血管面积密度（r = 0.127）相关。孟德尔随机化表明存在双向因果关系。基因预测较高的血管密度与视网膜各层厚度的增加有关，内层/外段+感光层厚度的标准化效应大小为1.50。基因预测视网膜层厚度的增加，特别是外丛状层，与更高的血管密度（标准化效应值0.45）和分形维数（标准化效应值0.48）有关。结论sgc - ipl和INL与血管密度和管径呈正相关。多维关系表明视网膜血管和神经参数之间的互补性质，突出了它们作为复合生物标志物的价值。孟德尔随机化揭示了双向因果关系，为针对血管和神经元成分的新治疗方法提供了见解。

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引用次数: 0

A theoretical model for oxygen transport to the cerebral cortex: effects of flow redistribution by penetrating arterioles 氧向大脑皮层输送的理论模型：穿透小动脉对血流再分配的影响

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-06-26 DOI: 10.1016/j.mvr.2025.104836

Akshita Sharma , Timothy W. Secomb

The goal of this study is to analyze the effects of changes of blood flow in penetrating arterioles (PAs) on the spatial distribution of tissue oxygen levels in the cerebral cortex. A theoretical model is used to simulate blood flow and oxygen transport in the cortical microcirculation. Networks containing up to 20,000 vessel segments, covering regions up to 1.1 mm², are generated by combining multiple hexagonal units, each fed by one PA. Varying numbers of adjacent PAs are constricted to 50 % of their original diameters, resulting in PA flow reduction by 93 %. With constriction of one or two PAs, the predicted minimum oxygen partial pressure is in the range 10–20 mmHg, corresponding to mild hypoxia. When three or more adjacent PAs are constricted, severe hypoxia (partial pressure below 10 mmHg) is predicted. Thus, oxygenation of the cortex is predicted to be only mildly affected by flow reduction in isolated PAs, but vulnerable to flow reduction in multiple adjacent PAs. Further simulations are used to explore the effects of flow redistribution while holding overall perfusion constant. If one PA is constricted and one adjacent PA is dilated, mild hypoxia is present. With three PAs constricted and four adjacent PAs dilated, regions of both mild and severe hypoxia are predicted. These results show that redistribution of blood flow, caused for instance by disruption of mechanisms for local blood flow regulation, can result in tissue hypoxia, even in the absence of reduced perfusion.

本研究的目的是分析穿透性小动脉血流变化对大脑皮层组织氧水平空间分布的影响。用理论模型模拟了皮层微循环中的血流和氧运输。网络包含多达20,000个容器段，覆盖面积达1.1 mm2，由多个六边形单元组合而成，每个单元由一个PA馈送。不同数量的相邻PA被压缩到原始直径的50%，导致PA流量减少93%。当一个或两个pa收缩时，预测最小氧分压在10-20 mmHg范围内，对应轻度缺氧。当三个或更多相邻的PAs收缩时，预测严重缺氧（分压低于10mmhg）。因此，预计皮质的氧合仅受到孤立pa的流量减少的轻微影响，但容易受到多个相邻pa的流量减少的影响。进一步的模拟用于探索在保持总灌注恒定的情况下流动再分配的影响。如果一个PA收缩，相邻的一个PA扩张，则存在轻度缺氧。3个PAs收缩，4个相邻PAs扩张，预测轻度和重度缺氧区域。这些结果表明，即使在没有减少灌注的情况下，由于局部血流调节机制的破坏而引起的血流重新分配也会导致组织缺氧。

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引用次数: 0

Predictive value of the average three-vessel microvascular resistance in patients with non-ST-segment elevation myocardial infarction after percutaneous coronary intervention 非st段抬高型心肌梗死经皮冠状动脉介入治疗后平均三支微血管阻力的预测价值。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-06-26 DOI: 10.1016/j.mvr.2025.104838

Ruijin Hong , Beilei Li , Hui Chen , Jiaxin Zhong , Yuxiang Chen , Yuanming Yan , Lianglong Chen , Qin Chen , Yukun Luo

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.

目的：探讨三主血管平均微血管阻力（3VA-AMR）对经皮冠状动脉介入治疗（PCI）后非st段抬高型心肌梗死（NSTEMI）患者预后的预测价值。方法：本研究于2021年3月1日至2022年2月28日在福建医科大学协和医院行PCI的NSTEMI患者进行。对所有患者PCI血管造影图像进行定量血流比（QFR）分析，评估术后三条主要血管的QFR和血管微血管阻力（AMR）。所有入组患者根据冠状动脉微血管功能障碍（CMD）标准分为高3VA-AMR组和低3VA-AMR组。主要终点是2年主要不良心脏事件（mace），包括心血管死亡、心肌梗死和缺血驱动的血运重建术。结果：290例患者纳入最终分析。与低3VA-AMR组相比，高3VA-AMR组三支血管狭窄程度较低（49.46 ± 13.70 %比52.93 ± 15.43 %,P = 0.001），QFR值较高（0.92±0.05比0.88±0.09,P < 0.001）， AMR值较高（274.50 [257.33-301.42]mmHg*s/m比208.00 [182.00-231.83]mmHg*s/m, P < 0.001）。高3VA-AMR组2年mace发生率显著高于低3VA-AMR组（21.90 % vs. 10.27 %,P = 0.007）。单因素和多因素Cox回归分析证实3VA-AMR与2年mace独立相关（HR:1.007, 95 % CI:1.004-1.010, P ）结论：3VA-AMR是NSTEMI患者2年mace的独立危险因素。与靶血管AMR相比，3VA-AMR对PCI术后2年mace的预测价值更高。

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引用次数: 0

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