Microvascular research最新文献_第9页

Interplay between platelet and T lymphocyte after coronary artery bypass grafting (CABG): Evidence for platelet mediated post-CABG immunomodulation 冠状动脉旁路移植术（CABG）后血小板和T淋巴细胞的相互作用：血小板介导的CABG后免疫调节的证据。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-03-17 DOI: 10.1016/j.mvr.2025.104805

Fateme Farhid , Ehteramolsadat Hosseini , Faranak Kargar , Mehran Ghasemzadeh

Background

On-pump coronary artery bypass grafting (CABG) triggers inflammatory responses as a result of surgical stress and extracorporeal circulation, which affect platelet and leukocyte activation while enhancing their intimate crosstalk. Given this, the study presented here aimed to investigate platelet-T cell interaction after CABG focusing on the changes in immunomodulatory subtypes of regulatory T Cells.

Methods

Blood samples were obtained from twenty patients undergoing on-pump CABG at 5 different time points of 24 h before, immediately, 2 h, 24 h, and one week after surgery. Total leukocyte and lymphocyte counts were determined using an automatic cell counter. Platelet P-selectin expression, frequencies of CD4⁺ and CD8⁺ T cells, platelet-T cell aggregates (PTCAs), and regulatory T cells derived from CD4⁺ (T4reg) and CD8⁺ (T8reg) cells, were assessed by flow cytometry.

Results

A significant increase in total leukocyte count occurred immediately after CABG, whereas, conversely, lymphocyte and CD4⁺ T cells but not CD8⁺ T cells decreased 2 h after surgery. However, all these changes returned to pre-CABG baseline levels within a week. Platelet P-selectin expression increased immediately after surgery, followed by a two-hour delay after PTCA, and both returned to baseline after one week. T4regs and T8regs showed a similar increase and decrease trend, where T8regs but not T4regs returned to baseline one week after surgery.

Conclusion

CABG surgery induces an inflammatory response that activates platelets and enhances P-selectin expression, facilitating PTCA formation. This mechanism is critical for the dynamics and differentiation of T cells, which play an essential role in post-CABG modulation of immune responses.

背景：无泵冠状动脉旁路移植术（CABG）由于手术应激和体外循环而引发炎症反应，影响血小板和白细胞的激活，同时增强它们之间的亲密串扰。鉴于此，本研究旨在研究CABG后血小板与T细胞的相互作用，重点关注调节性T细胞免疫调节亚型的变化。方法：选取20例行无泵搭桥患者，分别于术前24 h、即刻、2 h、24 h、术后1周5个不同时间点采血。总白细胞和淋巴细胞计数用自动细胞计数器测定。通过流式细胞术评估血小板p选择素的表达、CD4+和CD8+ T细胞、血小板-T细胞聚集体（PTCAs）和CD4+ (T4reg)和CD8+ (T8reg)细胞衍生的调节性T细胞的频率。结果：CABG术后立即出现白细胞总数显著增加，相反，术后淋巴细胞和CD4+ T细胞减少2 h，而CD8+ T细胞没有减少。然而，所有这些变化在一周内恢复到cabg前的基线水平。血小板p -选择素的表达在手术后立即升高，PTCA后延迟两小时，一周后恢复到基线水平。T4regs和T8regs表现出相似的增减趋势，术后1周T8regs恢复到基线水平，而T4regs未恢复。结论：CABG手术诱导炎症反应，激活血小板，提高p -选择素的表达，促进PTCA的形成。这一机制对T细胞的动力学和分化至关重要，在cabg后的免疫反应调节中发挥重要作用。

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引用次数: 0

Plasma neutrophil gelatinase-associated lipocalin level as a predictor of atherosclerotic cardiovascular disease risk in patients undergoing catheterization 血浆中性粒细胞明胶酶相关脂钙蛋白水平作为导管置入术患者动脉粥样硬化性心血管疾病风险的预测因子

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-02-24 DOI: 10.1016/j.mvr.2025.104797

Fadia Mayyas

Background

Atherosclerotic cardiovascular diseases (ASCVDs) represent a global health burden contributing to substantial morbidity and mortality. The neutrophil gelatinase-associated lipocalin (NGAL), a small glycoprotein, is secreted by inflammatory neutrophils, macrophages, and dendritic cells, playing a role in inflammation. However, its relevance as a predictor of ASCVDs risk across patients from low to very high-risk, and correlation with the need for revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) remains largely unexplored. Our objective was to assess plasma NGAl levels in patients with low to very high risk of ASCVD and their relationship with the severity of CAD and the requirement for revascularization.

Methods

Outpatients and patients undergoing catheterization were categorized into low, moderate, high, and very high risk of ASCVD. Plasma levels of NGAL were measured using ELISA and analyzed in relation to CAD status and the need for revascularization by PCI or CABG.

Results

Plasma NGAl levels were elevated in CAD patients, with higher levels in patients with acute coronary syndrome compared to those with stable angina. A gradual increase in plasma NGAl levels was noted with the elevated risk of ASCVD and degree of coronary artery stenosis. Notably, plasma NGAl level was independently correlated with ASCVD risk and the need for revascularization by PCI.

Conclusion

Our study indicates that plasma NGAl levels are linked to the risk of ASCVD and may help predict the development and severity of CAD. Further research targeting NGAL could explore its potential to mitigate the risk of ASCVD.

背景：动脉粥样硬化性心血管疾病（ascvd）是导致大量发病率和死亡率的全球性健康负担。中性粒细胞明胶酶相关脂钙蛋白（NGAL）是一种小糖蛋白，由炎症中性粒细胞、巨噬细胞和树突状细胞分泌，在炎症中起作用。然而，其作为低至高危患者ascvd风险预测指标的相关性，以及与经皮冠状动脉介入治疗（PCI）或冠状动脉搭桥手术（CABG）的血运重建术需求的相关性在很大程度上仍未被探索。我们的目的是评估低至极高ASCVD风险患者血浆NGAl水平及其与CAD严重程度和血运重建需求的关系。方法：将门诊患者和导管置入术患者分为ASCVD低、中、高、高危组。采用ELISA法测定血浆NGAL水平，并分析其与冠心病状态和PCI或CABG血运重建需求的关系。结果：冠心病患者血浆NGAl水平升高，急性冠状动脉综合征患者血浆NGAl水平高于稳定型心绞痛患者。血浆NGAl水平随着ASCVD风险和冠状动脉狭窄程度的升高而逐渐升高。值得注意的是，血浆NGAl水平与ASCVD风险和PCI血运重建需求独立相关。结论：我们的研究表明血浆NGAl水平与ASCVD的风险有关，并可能有助于预测CAD的发展和严重程度。针对NGAL的进一步研究可以探索其降低ASCVD风险的潜力。

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引用次数: 0

Imaging the microvasculature using nailfold capillaroscopy in patients with coronavirus disease-2019; A cross-sectional study 冠状病毒病-2019患者的甲襞毛细血管镜成像横断面研究。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-02-15 DOI: 10.1016/j.mvr.2025.104796

S. Wilkinson , J. Wilkinson , A. Grace , D. Lyon , M. Mellor , T. Yunus , J. Manning , G. Dinsdale , M. Berks , S. Knight , N. Bakerly , A. Gebril , P. Dark , A. Herrick , C. Taylor , M. Dickinson , A. Murray

Objectives

It is understood that microvascular dysfunction plays a key role in the pathogenesis of SARS-CoV-2 coronavirus disease (COVID-19). The aim of this study was to evaluate the usefulness of an automated, quantitative nailfold capillaroscopy system in identifying microvascular changes in those confirmed with or having had COVID-19.

Methods

Ninety-seven participants were enrolled into this study and grouped as follows: 52 participants with acute COVID-19 (further grouped by disease severity) and 45 participants with convalescent COVID-19 (further grouped into long COVID i.e. symptoms beyond 12 weeks, and fully recovered). Nailfold capillaroscopy images were obtained from the bilateral ring fingers using a Dino-Lite CapillaryScope 200 Pro, a small USB handheld microscope. Images were assessed quantitatively using bespoke automated measurement software and the number of haemorrhages noted for each participant.

Results

Capillaries were predominantly ‘normal’ in appearance with narrow capillary loops and evenly distributed, but with an increased number of haemorrhages (40 % in the convalescent group and 17 % in the acute group, p = 0.007). There was no statistically significant difference in the mean width of capillaries (20.9–21.8 μm) or vessel density (9.6–9.9 caps/mm; acute and convalescent group, respectively).

Conclusions

This study has demonstrated the feasibility of nailfold capillaroscopy at the critical care bedside. Capillary structure appeared normal across all groups of individuals affected by COVID-19. Although the small differences in the microvasculature in recovered patients compared to in acutely unwell patients may suggest delayed structural change due to COVID-19, these differences are unlikely to be clinically relevant. Longitudinal studies would be required to explore this in more detail.

研究目的据了解，微血管功能障碍在 SARS-CoV-2 冠状病毒病（COVID-19）的发病机制中起着关键作用。本研究的目的是评估自动定量甲襞毛细血管镜系统在识别确诊为 COVID-19 或曾患 COVID-19 的患者的微血管变化方面的实用性：本研究共招募了 97 名参与者，并将其分组如下：52名参与者患有急性COVID-19（根据疾病严重程度进一步分组），45名参与者患有恢复期COVID-19（进一步分为长期COVID，即症状超过12周且完全恢复）。使用小型 USB 手持显微镜 Dino-Lite CapillaryScope 200 Pro 获取双侧无名指的甲沟毛细血管镜图像。使用定制的自动测量软件对图像进行定量评估，并记录每位参与者的出血数量：结果：毛细血管外观主要 "正常"，毛细血管环狭窄，分布均匀，但出血数量增加（康复组为 40%，急性组为 17%，P = 0.007）。毛细血管的平均宽度（20.9-21.8 μm）和血管密度（9.6-9.9 个/mm；急性组和康复组分别为 9.6-9.9 个/mm）在统计学上没有明显差异：这项研究证明了在重症监护床旁进行甲襞毛细血管镜检查的可行性。所有受 COVID-19 影响的人群的毛细血管结构均正常。虽然康复患者的微血管与急性不适患者的微血管相比存在微小差异，这可能表明 COVID-19 导致的结构延迟变化，但这些差异不太可能与临床相关。需要进行纵向研究来更详细地探讨这一问题。

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引用次数: 0

Alternate local skin cooling and heating ameliorates impaired forearm skin vasodilation function mediated by prolonged sitting 交替局部皮肤冷却和加热改善受损的前臂皮肤血管舒张功能介导的久坐。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-02-13 DOI: 10.1016/j.mvr.2025.104795

Yudai Tomita , Kaname Tagawa , Takeshi Nishiyasu , Naoto Fujii

Prolonged sitting can impair physiological functions. We hypothesized that prolonged sitting attenuates forearm cutaneous vascular function but alternating local skin cooling and heating mitigates this attenuation. Eleven young adults (five women) sat for 75 min in thermoneutral condition (25 °C) during which skin temperature at four forearm skin sites was modulated: 1) maintained at 33 °C (control), 2) reduced to 15 °C for 4 min, then rised to 40 °C, repeated 5 times, 3) maintained at 33 °C for 4 min, then rised to 40 °C for 4 min, repeated 5 times or 4) elevated to 40 °C. Before and after 75-min prolonged sitting, venoarteriolar reflex (VAR) was assessed by a reduction in cutaneous blood flow (laser Doppler flowmetry) mediated by venous occlusion, whereas post-occlusive reactive hyperemia (PORH) was assessed by increases in cutaneous blood flow following arterial occlusion. After prolonged sitting, PORH decreased at the control (mean with 95%CI: 40.2 [34.5, 45.9] %max vs. 26.3 [19.3, 33.3] %max P < 0.001), but this response was not seen at the site subjected to alternating 15 °C cooling and 40 °C heating (P = 0.983). VAR remained unchanged before and after prolonged sitting at the control (P = 0.990), but increased with 15 °C cooling and 40 °C heating (−47.8 [−61.6, −34.1] %baseline vs. -68.0 [−75.3, −60.7] %baseline P = 0.029). We show that prolonged sitting decreases forearm cutaneous vasodilation function (PORH), but this response is mitigated by alternating local skin cooling and heating. Additionally, prolonged sitting does not affect forearm cutaneous VAR, but alternating local skin cooling and heating enhances VAR.

久坐会损害生理功能。我们假设久坐会减弱前臂皮肤血管功能，但局部皮肤交替冷却和加热会减轻这种减弱。11 名年轻成年人（5 名女性）在恒温（25 °C）条件下坐了 75 分钟，在此期间，四个前臂皮肤部位的皮肤温度被调节：1）保持 33 °C（对照组）；2）降至 15 °C，持续 4 分钟，然后升至 40 °C，重复 5 次；3）保持 33 °C，持续 4 分钟，然后升至 40 °C，持续 4 分钟，重复 5 次；或 4）升至 40 °C。在久坐 75 分钟之前和之后，静脉闭塞导致的皮肤血流减少（激光多普勒血流测量仪）评估了静脉小动脉反射（VAR），而动脉闭塞后皮肤血流增加评估了闭塞后反应性充血（PORH）。久坐后，PORH 在对照组时有所下降（平均值和 95%CI: 40.2 [34.5, 45.9] %max vs. 26.3 [19.3, 33.3] %maxP

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引用次数: 0

Novel 2D/3D vascular biomarkers reveal association between fundus changes and coronary heart disease 新的2D/3D血管生物标志物揭示眼底变化与冠心病之间的关联

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-02-10 DOI: 10.1016/j.mvr.2025.104793

Xiaoyu Dong , Yu Zou , Xiaohui Li , Na Su , Yuchen Wen , Jiale Fang , Xianqi Li , Qiang Chen , Junhong Wang

Purpose

To compare structural and vascular differences in the macular region of the retina using optical coherence tomography (OCT)/OCT angiography (OCTA) between coronary angiography (CAG)-confirmed coronary heart disease (CHD) patients and non-CHD individuals.

Methods

The study included 340 eyes from 180 CHD patients and 136 eyes from 68 controls. Imaging was conducted using the AngioVue OCT device with a macula-centered 6 mm ∗ 6 mm field of view. Retinal thickness and 2D/3D vascular-related biomarkers were derived using existing retinal layer segmentation software, and our previously proposed 2D/3D vascular and 3D foveal avascular zone segmentation methods. Statistical analyses included t-tests, Mann-Whitney U tests, chi-square tests, and Pearson's correlation.

Results

The CHD group exhibited significantly lower retinal nerve fiber layer (RNFL) thickness (r = −0.20, P < 0.001) in the inner inferior (I) region, based on macular region layer segmentation. For the 3D OCT images, as defined by the ETDRS grid, both the inner and outer retina layers in the outer superior (out-S) region were significantly thinner in the CHD group. The CHD group showed significantly lower overall 2D fractal dimension (FD) (1.72 ± 0.03 vs. 1.73 ± 0.02, P < 0.001) and vessel skeleton density (VSD) (26.61 ± 4.52 vs. 28.50 ± 3.40, P < 0.001) compared to the control group. The proposed 3D vascular density (VD) feature showed a significant difference between the groups (19.23 ± 5.67 vs. 20.69 ± 5.15, P = 0.048).

Conclusion

Thinning of retinal thickness and reduced vascular density are associated with CHD and may serve as valuable, cost-effective biomarkers for assessing coronary artery disease assessment.

目的利用光学相干断层扫描(OCT)/OCT血管造影（OCTA）技术比较冠心病（冠心病）患者与非冠心病患者视网膜黄斑区结构和血管的差异。方法采用180例冠心病患者340只眼和68例对照组136只眼。成像采用以黄斑为中心的6mm * 6mm视场的AngioVue OCT装置。视网膜厚度和2D/3D血管相关生物标志物使用现有的视网膜层分割软件，以及我们之前提出的2D/3D血管和3D中央凹无血管区分割方法。统计分析包括t检验、Mann-Whitney U检验、卡方检验和Pearson相关检验。结果冠心病组视网膜神经纤维层（RNFL）厚度显著降低(r = - 0.20, P <；0.001)，基于黄斑区域层分割。在3D OCT图像中，根据ETDRS网格的定义，冠心病组外上（out-S）区视网膜内外层均明显变薄。冠心病组总体二维分形维数（FD）显著低于冠心病组(1.72±0.03 vs. 1.73±0.02,P <；0.001)和血管骨架密度（VSD）(26.61±4.52∶28.50±3.40,P <；0.001)，与对照组相比。三维血管密度（VD）特征组间差异有统计学意义（19.23±5.67 vs. 20.69±5.15,P = 0.048）。结论视网膜厚度变薄和血管密度降低与冠心病相关，可作为评估冠状动脉疾病的有价值、有成本效益的生物标志物。

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引用次数: 0

Transplantation of autologous endothelial progenitor cells promotes the repair of fusiform aneurysms 自体内皮祖细胞移植促进梭状动脉瘤的修复。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-02-07 DOI: 10.1016/j.mvr.2025.104794

Lianfu Zhang , Shihui Ni , Weiwen Zhang , Jian Shi , Jun Ding , Xudong Xu , Shengbang Zhang , Yongming Zhang , Tao Jiang

Endothelial progenitor cells (EPCs), which are precursors for endothelial cells, possess the capability of repairing vascular damage and predicting the extent of early vascular injury. However, the role of EPCs in the repair of fusiform aneurysms is not clear. Here, we constructed a fusiform aneurysm model using pancreatic elastase digestion and validated the improvement effect of EPCs through histological staining and immunofluorescence. HE staining and elastic fiber staining showed destruction of the tunica adventitia in the fusiform aneurysm, marked dilatation of the arterial lumen, and thinning of the elastic lamina in the fusiform aneurysm. In the fusiform aneurysm group, the concentration of vascular endothelial growth factor (VEGF) was notably decreased compared to both the control and the saline group. The level of EPCs in the peripheral blood was decreased in the model group. Transplantation of EPCs into fusiform aneurysms promoted vascular repair, indicated by the decrease of myeloperoxidase (MPO), advanced oxidation protein products (AOPP), matrix metalloproteinase-9 (MMP-9), platelet factor 4 (PF4), and Fe²⁺. The level of VEGF was also elevated after EPCs transplantation. Finally, we noted a marked rise in lactate level in the peripheral blood of fusiform aneurysms. Lactate treatment led to an elevation of H3K18la levels in EPCs and inhibited cell proliferation. In conclusion, this study discovered that in mice with fusiform aneurysms, elevated lactate levels in the peripheral blood trigger histone lactylation, such impeding the proliferation of EPCs. Transplantation of EPCs into fusiform aneurysms facilitated aneurysm repair. These findings lay the groundwork for EPCs in the treatment of fusiform aneurysms.

内皮祖细胞（Endothelial progenitor cells, EPCs）是内皮细胞的前体，具有修复血管损伤和预测早期血管损伤程度的功能。然而，内皮祖细胞在梭状动脉瘤修复中的作用尚不清楚。本研究采用胰腺弹性酶消化法构建梭状动脉瘤模型，并通过组织染色和免疫荧光验证EPCs的改善作用。HE染色和弹性纤维染色显示梭状动脉瘤外膜破坏，动脉管腔明显扩张，梭状动脉瘤弹性层变薄。梭状动脉瘤组血管内皮生长因子（VEGF）浓度较对照组和生理盐水组明显降低。模型组大鼠外周血EPCs水平降低。EPCs移植梭状动脉瘤促进血管修复，表现为髓过氧化物酶（MPO）、晚期氧化蛋白产物（AOPP）、基质金属蛋白酶-9 （MMP-9）、血小板因子4 （PF4）和Fe2+的降低。内皮祖细胞移植后VEGF水平升高。最后，我们注意到梭状动脉瘤外周血乳酸水平显著升高。乳酸处理导致EPCs中H3K18la水平升高并抑制细胞增殖。总之，本研究发现，在梭状动脉瘤小鼠中，外周血乳酸水平升高会触发组蛋白乳酸化，从而阻碍EPCs的增殖。梭状动脉瘤内内皮祖细胞移植促进动脉瘤修复。这些发现为EPCs治疗梭状动脉瘤奠定了基础。

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引用次数: 0

Feasibility of a method for measurement of retinal pulse-propagated wave velocity in humans 一种测量人体视网膜脉冲传播波速的方法的可行性

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-02-06 DOI: 10.1016/j.mvr.2025.104792

Zhengxin Tang , Anthony E. Felder , Mahnaz Shahidi

Blood flow regulation has been shown to be compromised in common ocular diseases, such as diabetic retinopathy and glaucoma. The capacity of the retinal vessels to regulate blood flow can potentially serve as an oculomics biomarker for evaluating ocular and systemic diseases. Pulse-propagated intravascular pressure waves cause deformations of the vessel walls, thus offering a means to interrogate vascular compliance. The purpose of the current study is to report a method for measuring retinal pulse-propagated wave velocity (rPWV) based on spectral analysis of pulsatile intensity waveforms in human circumpapillary retinal vasculature. Arterial and venous rPWV values, as well as inter-subject variabilities of rPWV in non-diabetic and diabetic subjects, are reported. Preliminary results demonstrated the feasibility of this method for measuring rPWV and its potential for assessment of vascular plasticity in response to blood flow changes due to ocular and systemic diseases.

血流调节已被证明在常见的眼部疾病中受到损害，如糖尿病视网膜病变和青光眼。视网膜血管调节血流的能力可以作为评估眼部和全身性疾病的眼组学生物标志物。脉冲传播的血管内压力波引起血管壁变形，从而提供了一种询问血管顺应性的手段。本研究的目的是报告一种基于人类乳头状视网膜周围血管脉冲强度波形的频谱分析来测量视网膜脉冲传播波速（rPWV）的方法。报告了动脉和静脉rPWV值，以及非糖尿病和糖尿病受试者中rPWV的受试者间变异。初步结果表明，该方法可用于测量rPWV，并可用于评估眼部和全身疾病引起的血流变化对血管可塑性的影响。

引用次数: 0

Focal adhesion kinase mediates microvascular leakage and endothelial barrier dysfunction in ischemia-reperfusion injury 局灶黏附激酶介导缺血再灌注损伤微血管渗漏和内皮屏障功能障碍。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-01-28 DOI: 10.1016/j.mvr.2025.104791

Rebecca Patrick , Briana D. Pando , Clement Yang, Alexandra Aponte, Fang Wang, Tom Ewing, Yonggang Ma, Sarah Y. Yuan, Mack H. Wu

Intestinal ischemia-reperfusion (I/R) injury occurs under various surgical or disease conditions, where tissue hypoxia followed by reoxygenation results in the production of oxygen radicals and inflammatory mediators. These substances can target the endothelial barrier, leading to microvascular leakage. In this study, we induced intestinal I/R injury in mice by occluding the superior mesenteric artery, followed by removing the clamp to resume blood circulation. We assessed microvascular permeability to plasma proteins in vivo using intravital microscopy, measuring the time-dependent tracer distribution in the intravascular versus extravascular space in the mouse mesentery. Additionally, we examined endothelial cell-cell adhesive barrier resistance and junction morphology in cultured endothelial cell monolayers. At the molecular level, FAK inhibition similarly inhibited endothelial junction opening and barrier dysfunction in response to hydrogen peroxide-induced oxidative stress. To further investigate FAK's role with tissue/cell specificity, we developed an endothelial-specific inducible FAK knockout mouse model by crossbreeding FAK-floxed (FAK^fl/fl) mice with Tie-2-CreER^T2 transgenic mice. Compared to their wild-type controls, endothelial-specific FAK-deficient mice showed a blunted microvascular hyperpermeability response following I/R injury in the gut. Overall, our study demonstrates that FAK plays a significant signaling role in mediating endothelial barrier dysfunction and microvascular leakage during ischemia-reperfusion injury.

肠缺血-再灌注（I/R）损伤发生在各种手术或疾病条件下，组织缺氧后再氧化导致氧自由基和炎症介质的产生。这些物质可以靶向内皮屏障，导致微血管渗漏。在本研究中，我们通过闭塞肠系膜上动脉诱导小鼠肠I/R损伤，然后移除夹子以恢复血液循环。我们使用活体显微镜评估了体内微血管对血浆蛋白的渗透性，测量了小鼠肠系膜血管内和血管外空间的时间依赖性示踪剂分布。此外，我们在培养的内皮细胞单层中检测了内皮细胞-细胞粘附屏障阻力和连接形态。在分子水平上，FAK抑制类似地抑制内皮连接开放和屏障功能障碍，以响应过氧化氢诱导的氧化应激。为了进一步研究FAK在组织/细胞特异性中的作用，我们通过将FAK-floxed （FAKfl/fl）小鼠与Tie-2-CreERT2转基因小鼠杂交，建立了内皮特异性诱导FAK敲除小鼠模型。与野生型对照相比，内皮特异性fak缺陷小鼠在肠道I/R损伤后表现出迟钝的微血管高通透性反应。总之，我们的研究表明，在缺血再灌注损伤过程中，FAK在介导内皮屏障功能障碍和微血管渗漏中起着重要的信号传导作用。

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引用次数: 0

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-01-19 DOI: 10.1016/j.mvr.2025.104783

Freya Richter , Moa Nilsson , Joakim Henricson , Carl Johan Östgren , Marcus Larsson , Tomas Strömberg , Ingemar Fredriksson , Fredrik Iredahl

Introduction

Little is known about the day-to-day variability of different skin microcirculation parameters, and how this variability is influenced by age and sex. The aim was to examine the day-to-day variability of microcirculatory parameters in relation to age and sex.

Methods

The cutaneous microcirculation was measured using a fiber optic probe integrating laser Doppler flowmetry (LDF) and diffuse reflectance spectroscopy (DRS) to measure oxygen saturation, red blood cell (RBC) tissue fraction, speed-resolved and conventional perfusion. Measurements at two separate days were compared during baseline, a 5-min occlusion and during the following post-occlusive reactive hyperemia (PORH) period on the volar forearm and dorsal foot in totally 48 men and women aged 20–30 and 50–60 years, respectively. Variability was expressed as the coefficient of variation CV and repeatability as the intraclass correlation coefficient ICC.

Results

Peak oxygen saturation during PORH had the lowest day-to-day variability for the forearm (CV = 2.1 %) and the foot (CV = 3.8 %) as well as an excellent repeatability (ICC = 0.80 and ICC = 0.82, respectively). Older women had a higher day-to-day variability in baseline conventional perfusion compared to younger women on the forearm (p = 0.007). On the foot, older women had a lower day-to-day variability than younger women for baseline oxygen saturation (p = 0.006) and peak RBC tissue concentration (p = 0.008). Older men had a lower day-to-day variability than younger men for baseline oxygen saturation (p = 0.012) but a higher variability for baseline and peak RBC tissue concentration (p = 0.008 and p = 0.002) on the foot.

Conclusion

Peak oxygen saturation had the lowest day-to-day variability of the measured parameters. A lower value of peak oxygen saturation has previously been associated with increasing systematic coronary risk implying that this is a suitable parameter for measuring microcirculatory dysfunction. Sex and age only affected the day-to-day variability of very few parameters.

导读：关于不同皮肤微循环参数的日常变化，以及这种变化如何受到年龄和性别的影响，我们所知甚少。目的是检查微循环参数的日常变化与年龄和性别的关系。方法：采用激光多普勒血流仪（LDF）和漫反射光谱（DRS）相结合的光纤探针测量皮肤微循环，测量血氧饱和度、红细胞组织分数、速度分辨和常规灌注。对48名年龄分别为20-30岁和50-60岁 岁的男性和女性在基线、5分钟闭塞和随后在前臂掌侧和足背的闭塞后反应性充血（PORH）期间的两天测量结果进行比较。变异性用变异系数CV表示，重复性用类内相关系数ICC表示。结果:高峰期间氧饱和度PORH最低日常可变性的前臂(CV = 2.1  %)和脚(CV = 3.8  %)以及一个优秀的可重复性(ICC = 0.80和ICC  = 0.82,分别)。与年轻女性相比，老年女性前臂基线常规灌注的日常变异性更高（p = 0.007）。在足部，老年女性的基线血氧饱和度（p = 0.006）和峰值红细胞组织浓度（p = 0.008）的日常变异性低于年轻女性。老年男性的每日基线血氧饱和度变异性低于年轻男性（p = 0.012），但足部基线和峰值红细胞组织浓度变异性较高（p = 0.008和p = 0.002）。结论：血氧饱和度峰值在测量参数中具有最低的逐日变异性。较低的峰值血氧饱和度与系统性冠状动脉风险增加有关，这意味着这是测量微循环功能障碍的合适参数。性别和年龄仅影响极少数参数的日常变异性。

{"title":"Sex and age-related day-to-day variability in the skin microcirculation during post-occlusive reactive hyperemia","authors":"Freya Richter , Moa Nilsson , Joakim Henricson , Carl Johan Östgren , Marcus Larsson , Tomas Strömberg , Ingemar Fredriksson , Fredrik Iredahl","doi":"10.1016/j.mvr.2025.104783","DOIUrl":"10.1016/j.mvr.2025.104783","url":null,"abstract":"<div><h3>Introduction</h3><div>Little is known about the day-to-day variability of different skin microcirculation parameters, and how this variability is influenced by age and sex. The aim was to examine the day-to-day variability of microcirculatory parameters in relation to age and sex.</div></div><div><h3>Methods</h3><div>The cutaneous microcirculation was measured using a fiber optic probe integrating laser Doppler flowmetry (LDF) and diffuse reflectance spectroscopy (DRS) to measure oxygen saturation, red blood cell (RBC) tissue fraction, speed-resolved and conventional perfusion. Measurements at two separate days were compared during baseline, a 5-min occlusion and during the following post-occlusive reactive hyperemia (PORH) period on the volar forearm and dorsal foot in totally 48 men and women aged 20–30 and 50–60 years, respectively. Variability was expressed as the coefficient of variation CV and repeatability as the intraclass correlation coefficient ICC.</div></div><div><h3>Results</h3><div>Peak oxygen saturation during PORH had the lowest day-to-day variability for the forearm (CV = 2.1 %) and the foot (CV = 3.8 %) as well as an excellent repeatability (ICC = 0.80 and ICC = 0.82, respectively). Older women had a higher day-to-day variability in baseline conventional perfusion compared to younger women on the forearm (<em>p</em> = 0.007). On the foot, older women had a lower day-to-day variability than younger women for baseline oxygen saturation (<em>p</em> = 0.006) and peak RBC tissue concentration (<em>p</em> = 0.008). Older men had a lower day-to-day variability than younger men for baseline oxygen saturation (<em>p</em> = 0.012) but a higher variability for baseline and peak RBC tissue concentration (p = 0.008 and <em>p</em> = 0.002) on the foot.</div></div><div><h3>Conclusion</h3><div>Peak oxygen saturation had the lowest day-to-day variability of the measured parameters. A lower value of peak oxygen saturation has previously been associated with increasing systematic coronary risk implying that this is a suitable parameter for measuring microcirculatory dysfunction. Sex and age only affected the day-to-day variability of very few parameters.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"159 ","pages":"Article 104783"},"PeriodicalIF":2.9,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

X-ray microtomography imaging enables accurate visualization and quantification of the small-intestinal villi microvasculature – celiac disease as a model x射线显微断层成像能够精确地可视化和量化小肠绒毛微血管-乳糜泻作为模型。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-01-10 DOI: 10.1016/j.mvr.2025.104782

Aino Reunamo , Markus Hannula , Johannes Virta , Kalle Kurppa , Katri Lindfors , Jari Hyttinen

Vasculature of the small bowel mucosa, with a significant role in nutrient absorption and gut homeostasis, has been suggested to undergo remodeling in various gastrointestinal disorders, including celiac disease. However, due to its spatial organization within the mucosa, conventional 2D histological methods are of limited value in studying the intestinal vasculature reliably. X-ray microtomography (micro-CT) is a promising tool for soft tissue imaging, as it enables digital 3D reconstruction of various tissue samples, including endoscopically obtained small-bowel mucosal biopsies. In this proof-of-concept study, we utilize micro-CT imaging combined with iodine staining in revealing the 3D mucosal microvascular structures using celiac disease as a model. Furthermore, we present a unique image analysis workflow that enables the quantification of the microvascular network with explanatory parameters in untreated and treated celiac disease patients as well as in non-celiac disease controls. The calculation of these parameters has been unachievable previously using 2D image processing methods. The workflow produced results that showed noticeable differences in the microvascular structures from the point of diagnosis to after treatment. This unique method has potential to be used with various intestinal diseases and other applications where the mucosal vascular structures need to be visualized.

小肠粘膜血管在营养吸收和肠道稳态中发挥着重要作用，有研究表明，包括乳糜泻在内的各种胃肠道疾病都会导致小肠粘膜血管重塑。然而，由于其在粘膜内的空间组织，传统的二维组织学方法在可靠研究肠道血管方面价值有限。X 射线显微层析技术（micro-CT）是一种很有前途的软组织成像工具，因为它能对各种组织样本（包括内镜下获得的小肠粘膜活检样本）进行数字三维重建。在这项概念验证研究中，我们以乳糜泻为模型，利用微 CT 成像结合碘染色来揭示粘膜微血管的三维结构。此外，我们还介绍了一种独特的图像分析工作流程，该流程可对未经治疗和已接受治疗的乳糜泻患者以及非乳糜泻对照组的微血管网络进行量化，并提供解释性参数。以前使用二维图像处理方法无法计算这些参数。工作流程产生的结果显示，从诊断到治疗后，微血管结构存在明显差异。这种独特的方法可用于各种肠道疾病和其他需要观察粘膜血管结构的应用。

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引用次数: 0