Microvascular research最新文献

Functional heterogeneity of endothelium-dependent vasorelaxation in different order branches of mesenteric artery in female/male mice.

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2024-11-27 DOI: 10.1016/j.mvr.2024.104777

Luyun Zhang, Shaoya Rong, Hui Dong

Although the mouse mesenteric artery is widely used as a model of resistance vessels, it is unknown which order branch is the best representative and if there is a heterogeneity of vascular activity in different orders. We systematically compared the vasorelaxation between the mouse mesenteric artery's first- and second-order branches. The first- and second-order branches of the mesenteric artery (lumen diameter of >300 μm and 179.9 ± 11.1 μm, respectively) were taken from the location close to their branching points in wide-type (WT) and TRPV4^-/- (KO) mice. Vasorelaxation of the mesenteric artery was measured using a Danish DMT520A microvascular system. Acetylcholine (ACh) induced much greater vasorelaxation via TRPV4 channels/endothelium-dependent hyperpolarization (EDH/H₂S) in the second-order branch. The store-operated Ca²⁺ entry (SOCE) mediated much greater vasorelaxation via EDH in the second-order branch than that via NO in the first-order branch. However, capsaicin-induced vasorelaxation was much greater via TRPV1/NO and TRPV1/CGRP in the first-order branch than TRPV4/EDH only in the second-order branch. Moreover, sex differences in ACh-induced vasorelaxation were obviously in the first-order branch but marginally in the second-order branch. Mechanistically, the myoendothelial gap junction (MEGJ) is involved in ACh-induced vasorelaxation in the second-order branch but not in the first-order branch. However, endothelial IK_Ca and SK_Ca functions and endothelium-independent vasorelaxation were similar for both first- and second-order branches. TRPV1/NO/CGRP mediates endothelium-dependent vasorelaxation in the first-order branch as the best representative of conduit vessels, but TRPV4/EDH/H₂S mediates endothelium-dependent vasorelaxation in the second-order branch as the best representative of resistance vessels in mice.

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引用次数: 0

Pulse wave analysis as a tool to assess endothelial function following lipid lowering intervention in hypercholesterolemia 脉搏波分析作为评估高胆固醇血症患者降脂干预后内皮功能的一种工具。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2024-11-23 DOI: 10.1016/j.mvr.2024.104772

Nik Nor Izah Nik Ibrahim , Aida Hanum Ghulam Rasool , Razlina Abdul Rahman , Maryam Azlan , Aniza Abd Aziz

Background

Pulse wave analysis (PWA) assesses endothelial dependent vasodilation (EDV) via the change in augmentation index (AIx) and has been used as a tool to assess endothelial function. However, its effectiveness in assessing the response to lipid lowering treatment has not been evaluated. The study aimed to describe and correlate the change in EDV following lipid lowering intervention in patients with hypercholesterolemia.

Methods

48 newly diagnosed patients with hypercholesterolemia underwent 6 months intervention with statin and/or therapeutic lifestyle changes (TLC) in clinical setting. Lipid profile measurement and endothelial function assessment using PWA were performed pre- and post-intervention.

Results

Significant reductions in low density lipoprotein cholesterol (LDL-C), non-high density lipoprotein cholesterol (non-HDL-C) and total cholesterol (TC) with corresponding significant improvement in EDV (2.94 ± 3.69 % to 7.50 ± 3.79 %, p < 0.001) were observed following intervention. Sub-analyses revealed greater LDL-C reductions and EDV improvements in the statin group compared to TLC. There was a significant inverse correlation between the change in EDV and the change in LDL-C after intervention (r = −0.298, p = 0.040).

Conclusion

Endothelial function assessed by PWA showed a parallel change with lipid profile pattern following lipid lowering intervention. The simple and non-invasive method may provide a potential tool for evaluating endothelial function and treatment outcomes in patients with hypercholesterolemia.

背景：脉搏波分析（PWA）通过增强指数（AIx）的变化评估内皮依赖性血管舒张（EDV），已被用作评估内皮功能的工具。然而，它在评估降脂治疗反应方面的有效性尚未得到评估。方法：48 名新诊断的高胆固醇血症患者在临床环境中接受了为期 6 个月的他汀类药物和/或治疗性生活方式改变（TLC）干预。结果：低密度脂蛋白显著降低，而高密度脂蛋白则明显降低：结果：低密度脂蛋白胆固醇（LDL-C）、非高密度脂蛋白胆固醇（non-HDL-C）和总胆固醇（TC）明显降低，EDV（2.94 ± 3.69 % 至 7.50 ± 3.79 %，P 结论：通过使用他汀类药物和/或治疗性生活方式改变（TLC）对内皮功能进行评估，发现干预前后内皮功能明显改善（2.94 ± 3.69 % 至 7.50 ± 3.79 %，P 结论）：通过 PWA 评估的内皮功能与降脂干预后的血脂谱模式呈平行变化。这种简单、无创的方法可为评估高胆固醇血症患者的内皮功能和治疗效果提供一种潜在的工具。

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引用次数: 0

Retinal vascular alterations are associated with cognitive function and neuroimaging in white matter hyperintensities 视网膜血管改变与认知功能和白质高密度症的神经影像学相关。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2024-11-19 DOI: 10.1016/j.mvr.2024.104763

Rui Tao , Zhenyu Wei , Xiaoxia Chen , Qian Wang , Xiuduo Liu , Qing Lu , Jie Zhao , Hui Zhou

Aim

To reveal alterations in retinal structure, vessels, and function, and their association with cognitive function and neuroimaging in white matter hyperintensities (WMH).

Methods

This study enlisted WMH and age-matched healthy controls (HC). All participants underwent six different tests: magnetic resonance imaging (MRI) of the brain, the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), fundus photography, optical coherence tomography (OCT), and visual field testing. Visual field can reflect the function of optic nerve and retina. The peripapillary retinal nerve fiber layer (p-RNFL) was analyzed using OCT. Image J software was employed to measure retinal vascular caliber in fundus photographs and to compute the central retinal artery equivalent (CRAE), central retinal venous equivalent (CRVE) and arteriole-to-venule ratio (AVR).

Results

A total of 90 WMH patients and 93 HC participants. In comparison with the HC, the WMH group exhibited reduced cognitive function scores (MoCA: P < 0.001; MMSE: P < 0.001), narrower retinal arteries (P < 0.001), smaller AVR (P < 0.001) and thinner p-RNFL thickness (total: P = 0.026; temporal: P = 0.006). About visual field, both univariate and multivariate analysis showed that mean sensitivity decreased, and mean defect increased in WMH group (P < 0.05). Additionally, correlation analysis indicated a positive correlation between CRAE and AVR with MMSE and MoCA score (r = 0.424–0.57, P < 0.001) and a negative correlation with Fazekas score (CRAE: r = −0.515, P < 0.001; AVR: r = −0.554, P < 0.001), and p-RNFL was negatively correlated with Fazekas score (total p-RNFL: r = −0.192, P = 0.009; temporal p-RNFL: r = −0.217, P = 0.003). Notably, no significant correlation was found between cognitive function and p-RNFL.

Conclusion

WMH group exhibit narrower retinal arteries, smaller arteriole-to-venule ratio, damaged p-RNFL and visual function. These alterations in retinal vessels are associate with both neuroimaging and cognitive function. Our results suggest that retinal imaging could serve as a valuable instrument for evaluating WMH and provides some new approaches to study the characteristic markers of WMH.

目的：揭示白质高密度症（WMH）患者视网膜结构、血管和功能的改变及其与认知功能和神经影像学的关联：本研究招募了 WMH 和年龄匹配的健康对照组（HC）。所有参与者都接受了六项不同的测试：脑部磁共振成像（MRI）、迷你精神状态检查（MMSE）、蒙特利尔认知评估（MoCA）、眼底照相、光学相干断层扫描（OCT）和视野测试。视野可反映视神经和视网膜的功能。光学相干断层扫描分析了视网膜周围神经纤维层（p-RNFL）。使用 Image J 软件测量眼底照片中的视网膜血管口径，并计算视网膜中央动脉等值（CRAE）、视网膜中央静脉等值（CRVE）和动静脉比（AVR）：共有90名WMH患者和93名HC参与者。与 HC 相比，WMH 组患者的认知功能评分降低（MoCA：P 结论：WMH 组患者的视网膜变窄，而 HC 组患者的视网膜变窄：WMH 组表现出视网膜动脉变窄、动脉血管与小动脉之比变小、p-RNFL 和视觉功能受损。视网膜血管的这些改变与神经影像学和认知功能都有关联。我们的研究结果表明，视网膜成像可作为评估 WMH 的重要工具，并为研究 WMH 的特征标记提供了一些新方法。

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引用次数: 0

Cardioprotective effects of l-glutamine in an ischemic rat heart model 左旋谷氨酰胺对缺血大鼠心脏模型的心脏保护作用

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2024-11-19 DOI: 10.1016/j.mvr.2024.104764

Akiko Kawakami , Hiroaki Sato , Yosuke Nakadate , Patricia Roque , Arkady Khoutorsky , Takashi Matsukawa , Thomas Schricker

Introduction

l-glutamine has been shown to have cardioprotective effects in models of ischemia-reperfusion injury. Its potential cardioprotective effects when given before and during early reperfusion, however, have not been studied.

Methods

This study hypothesized that l-glutamine administered before and after myocardial ischemia provides better cardioprotection than when administered after ischemia only. Eighteen male rat hearts were exposed to 15 min of ischemia using the Langendorff system and randomly assigned to three groups of six each. Group one received Krebs-Henseleit (KH) buffer over 20 min before ischemia and during 20 min of reperfusion (Control), group two received KH buffer containing 2.5 mmol･L⁻¹ glutamine during reperfusion (Post-Gln) and group three was given KH buffer containing glutamine before and after the ischemic insult (Pre + Post-Gln). Indicators of hemodynamics such as maximum left ventricular derivative of pressure development (LV dP/dt max) were recorded at 5, 10, 15 and 20 min post-reperfusion. Myocardial levels of O-linked β-N-acetylglucosamine (O-GlcNAc) and heat shock protein 70 (HSP70) were measured by Western blotting technique after 20 min of reperfusion.

Results

The LV dp/dt max in the Pre + Post-Gln group was significantly elevated as compared to the Post-Gln group after 10 min of reperfusion and was significantly higher than in the control group at all-time points. Myocardial expression of O-GlcNAc was increased in the Pre + Post-Gln group (P < 0.01 vs. control) without showing any differences in HSP70.

Conclusion

In this model of stunned myocardium, pre- and post-ischemic administration of l-glutamine improved cardiac function indicating cardioprotective effects, possibly mediated by O-GlcNAc.

简介：在缺血再灌注损伤模型中，l-谷氨酰胺已被证明具有心脏保护作用。然而，在早期再灌注前和再灌注期间给予 l-谷氨酰胺时，其潜在的心脏保护作用尚未得到研究：本研究假设，在心肌缺血前后给予 l-谷氨酰胺比仅在缺血后给予 l-谷氨酰胺能更好地保护心脏。使用 Langendorff 系统将 18 只雄性大鼠的心脏暴露于 15 分钟的心肌缺血，并将其随机分配到三组，每组六只。第一组在缺血前 20 分钟和再灌注 20 分钟期间接受克雷布斯-亨斯勒（KH）缓冲液（对照组），第二组在再灌注期间接受含有 2.5 mmol・L-1 谷氨酰胺的 KH 缓冲液（Post-Gln 组），第三组在缺血前和缺血后接受含有谷氨酰胺的 KH 缓冲液（Pre + Post-Gln）。记录再灌注后 5、10、15 和 20 分钟的血液动力学指标，如左心室压力发展的最大导数（LV dP/dt max）。再灌注20分钟后，通过Western印迹技术测定心肌中O-连环β-N-乙酰葡糖胺（O-GlcNAc）和热休克蛋白70（HSP70）的水平：结果：再灌注10分钟后，与再灌注后组相比，再灌注前+再灌注后组的左心室dp/dt max明显升高，且在所有时间点均明显高于对照组。O-GlcNAc 的心肌表达在 Gln 前+Gln 后组有所增加（P 结论：O-GlcNAc 的表达在 Gln 前+Gln 后组明显高于对照组）：在这种心肌骤停模型中，缺血前后给予 l-谷氨酰胺可改善心脏功能，表明其具有心脏保护作用，这可能是由 O-GlcNAc 介导的。

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引用次数: 0

Statin-treated RBC dynamics in a microfluidic porous-like network 经他汀类药物处理的红细胞在微流体多孔网络中的动态变化。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2024-11-19 DOI: 10.1016/j.mvr.2024.104765

Antonios Stathoulopoulos , Carola S. König , Sudarshan Ramachandran , Stavroula Balabani

The impact of therapeutic interventions on red blood cell (RBC) deformability and microscale transport is investigated, using statins as an exemplar. Human RBCs were treated in vitro with two commonly prescribed statins, atorvastatin and rosuvastatin, at clinically relevant concentrations. Changes in RBC deformability were quantified using a microfluidic-based ektacytometer and expressed in terms of the elongation index. Dilute suspensions of the statin-treated RBCs were then perfused through a microfluidic pillar array, at a constant flow rate and negligible inertia, and imaged. Particle Tracking Velocimetry (PTV) was applied to track RBCs, identify preferential paths and estimate their velocities, whereas image processing was used to estimate cell dynamics, perfusion metrics and distributions. The findings were compared against those of healthy, untreated cells. Statins enhanced RBC deformability in agreement with literature. The extent of enhancement was found to be statin-dependent. The softer statin-treated cells were found to flow in straight, less tortuous paths, spend more time inside the pillar array and exhibit lower velocities compared to healthy RBCs, attributed to their enhanced deformation and longer shape recovery time upon impact with the array posts. The in vitro microfluidic approach demonstrated here may serve as a monitoring tool to personalise and maximise the outcome of a therapeutic treatment.

本研究以他汀类药物为例，研究了治疗干预对红细胞（RBC）变形性和微观运输的影响。用两种常用的他汀类药物（阿托伐他汀和罗苏伐他汀）以临床相关浓度对人类红细胞进行体外处理。使用基于微流体的埃克泰克计对红细胞变形性的变化进行量化，并用伸长指数表示。然后将他汀类药物处理过的RBC稀释悬浮液以恒定流速和可忽略的惯性灌注到微流体柱阵列中，并进行成像。粒子跟踪测速仪（PTV）用于跟踪 RBC、识别优先路径并估算其速度，而图像处理则用于估算细胞动态、灌注指标和分布。研究结果与未经处理的健康细胞进行了比较。他汀类药物增强了红细胞的变形能力，这与文献报道一致。增强的程度取决于他汀类药物。与健康的红细胞相比，他汀类药物处理过的软细胞的流动路径更直、更少迂回，在柱阵列内停留的时间更长，速度更低，这归因于它们在撞击柱阵列时变形增强，形状恢复时间更长。这里展示的体外微流体方法可作为一种监测工具，用于个性化和最大限度地提高治疗效果。

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引用次数: 0

A multimodal imaging approach to investigate retinal oxygen and vascular dynamics, and neural dysfunction in bietti crystalline dystrophy 用多模态成像方法研究 bietti 晶体营养不良症患者视网膜氧和血管动态以及神经功能障碍。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2024-11-08 DOI: 10.1016/j.mvr.2024.104762

Shiyi Yin , Jinyuan Wang , Jingyuan Zhu , Ximeng Feng , Haihan Zhang , Haowen Li , Jingying Xiu , Chuanqing Zhou , Qiushi Ren , Wenbin Wei

Background

This study aimed to explore retinal changes in Bietti crystalline dystrophy (BCD) patients, including retinal metabolism, blood flow, vascular remodeling, and pupillary light reflex (PLR) abnormalities.

Methods

This cross-sectional study included 120 eyes from BCD patients and 120 eyes from healthy controls, utilizing a multimodal imaging system (MEFIAS 3200, SYSEYE, Chongqing, China) to evaluate retinal oxygenation, blood flow, vascular structure, and PLR. Measurements included oxygen saturation, blood flow velocity, vessel diameters, and pulsatility metrics. PLR parameters were assessed under specific light stimuli.

Results

BCD patients demonstrated significantly higher retinal oxygen saturation and content, but lower oxygen utilization and metabolism compared to controls, with more pronounced declines in those over 40 years old. Vascular parameters revealed smaller external diameters and larger lumen diameters, indicating vascular remodeling. Retinal blood flow was lower, while the resistivity index was higher in BCD patients. Additionally, PLR abnormalities were noted, including reduced constriction amplitude, pupil constriction ratio, constriction duration, and maximum constriction velocity, along with prolonged latency were observed in BCD patients.

Conclusion

BCD patients had significant retinal and vascular changes, along with PLR impairments, especially in patients over 40. More targeted interventions should be focused in future research.

背景：本研究旨在探讨Bietti晶体营养不良症（BCD）患者视网膜的变化，包括视网膜代谢、血流、血管重塑和瞳孔对光反射（PLR）异常：这项横断面研究纳入了120名BCD患者和120名健康对照者，利用多模态成像系统（MEFIAS 3200，SYSEYE，中国重庆）评估视网膜氧合、血流、血管结构和瞳孔对光反射。测量项目包括血氧饱和度、血流速度、血管直径和脉动指标。PLR参数在特定光刺激下进行评估：结果：与对照组相比，BCD 患者的视网膜氧饱和度和含量明显较高，但氧利用率和新陈代谢较低，40 岁以上的患者下降更为明显。血管参数显示外径变小，管腔直径变大，表明血管重塑。BCD 患者的视网膜血流量较低，而电阻率指数较高。此外，BCD 患者还发现 PLR 异常，包括收缩幅度、瞳孔收缩比、收缩持续时间和最大收缩速度降低，以及潜伏期延长：结论：BCD 患者的视网膜和血管发生了明显变化，并伴有 PLR 损伤，尤其是 40 岁以上的患者。今后的研究应重点关注更有针对性的干预措施。

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引用次数: 0

Increased angiopoietin-1 improves nailfold capillary morphology in patients with systemic sclerosis 增加血管生成素-1可改善系统性硬化症患者的甲沟毛细血管形态。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2024-11-07 DOI: 10.1016/j.mvr.2024.104761

Yoshihito Shima , Akane Watanabe , Nobuto Inoue , Tetsuya Maruyama , Eiji Kunitomo , Yuji Matsushima , Atsushi Kumanogoh

Objective

Raynaud's phenomenon is a common symptom of systemic sclerosis. We previously reported that elbow heating increases angiopoietin-1 in the fingertips and alleviates Raynaud's phenomenon. Angiopoietin-1 levels decrease in patients with systemic sclerosis with severe capillary damage. We aimed to conduct a prospective study to confirm whether the increase in angiopoietin-1 caused by heating modifies capillary morphology.

Methods

The left ring fingers of 19 patients with systemic sclerosis were monitored six times at 4-week intervals using capillaroscopy, during which both elbows were heated using disposable heating pads for 8 weeks. Blood samples were collected from the same fingertips four times—before heating, twice during heating, and once after heating—to measure angiopoietin-1.

Results

In six patients, the peak increase in angiopoietin-1 occurred 4 weeks after the start of heating, whereas in seven patients, the peak value was observed 4 weeks after the termination thereof. No change in the density of the front-row capillaries was observed by capillaroscopy. The proportion of hairpin-shaped capillaries increased from 20.2 % during the preheating period to 26.6 % during the heating period (p = 0.00107). When a correlation coefficient of 0.6 or higher was set as significant, there was a strong correlation between changes in fingertip angiopoietin-1 levels and changes in the proportion of hairpin-shaped capillaries in six patients.

Conclusion

Increased angiopoietin-1 levels in the fingertip due to elbow heating may improve the peripheral capillary morphology in patients with systemic sclerosis.

目的：雷诺现象是系统性硬化症的常见症状：雷诺现象是系统性硬化症的一种常见症状。我们曾报道，肘部加热可增加指尖血管生成素-1，缓解雷诺现象。在毛细血管严重受损的系统性硬化症患者中，血管生成素-1的水平会下降。我们旨在进行一项前瞻性研究，以证实加热引起的血管生成素-1增加是否会改变毛细血管形态：方法：使用毛细血管镜对 19 名系统性硬化症患者的左手无名指进行了 6 次监测，每次间隔 4 周，在此期间使用一次性加热垫对双肘进行加热，持续 8 周。从同一指尖采集血液样本四次--加热前、加热过程中两次、加热后一次--测量血管生成素-1：结果：在 6 名患者中，血管生成素-1 的增长峰值出现在开始加热 4 周后，而在 7 名患者中，峰值出现在终止加热 4 周后。通过毛细血管镜观察，前排毛细血管的密度没有变化。发夹状毛细血管的比例从预热期的 20.2% 增加到加热期的 26.6%（p = 0.00107）。当相关系数达到或超过 0.6 时，6 名患者指尖血管生成素-1 水平的变化与发夹状毛细血管比例的变化之间存在很强的相关性：结论：肘部加热导致指尖血管生成素-1水平升高，可改善系统性硬化症患者的外周毛细血管形态。

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引用次数: 0

The role of the cyclooxygenase-2 pathway in tissue ischemia and revascularization following skeletal muscle injury induced by bothropic snake venom 环氧化酶-2通路在两种蛇毒引起的骨骼肌损伤后组织缺血和血管再通中的作用。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2024-11-05 DOI: 10.1016/j.mvr.2024.104760

Melissa Rodrigues Correia , Sang Won Han , Teresa Escalante , Vanessa Moreira

Bothrops asper venom (Bav) contains metalloproteinases that disrupt the microvascular system, impairing muscle tissue regeneration after injury. This study investigated the impact of the cyclooxygenase-2 (COX-2) pathway on vascular injury and revascularization in muscle injuries induced by Bav. Mice were injected with Bav into the gastrocnemius muscle and treated with lumiracoxib, a selective COX-2 inhibitor, 30 min, 2 days, and 6 days post-Bav injection. Muscle tissue was analyzed at 24 h, 7 days, and 21 days post-injection. A decrease in COX-2 expression at 24 h post-Bav injection indicated significant necrosis and tissue loss. Both Bav injection and lumiracoxib treatment influenced the decrease of prostaglandin (PG)D₂ and PGE₂ production. Seven and 21 days post-Bav injections, COX-2 expression increased, along with PGDs levels unaffected by lumiracoxib, indicating that the other isoform COX-1 pathway could contribute to the release of PGs. Bav/lumiracoxib treated animals presented exacerbated limb ischemia, implying that COX-2-derived prostaglandins preserve vessel integrity. CD31, an angiogenesis marker, initially (24 h) decreased post-Bav injection but increased at 7 and 21 days in Bav/lumiracoxib mice, suggesting a down-modulatory role for COX-2-derived prostaglandins in early angiogenesis and tissue regeneration. Vascular endothelial growth factor (VEGF) production rose 7 days post-Bav injection, supporting its role in angiogenesis. Previous treatment with lumiracoxib promoted release of VEGF levels 21 days post-Bav injury showing that the inhibition of COX-2 pathway in the early stage of revascularization stimulates the neovascularization regulated by elevated release of VEGF. Similarly, metalloproteinases (MMPs), such as MMP-9, MMP-10, and MMP-13, crucial for vascular remodeling, were elevated 21 days after Bav/lumiracoxib treatment. In conclusion, the COX-2 pathway is essential to decrease the high grade of ischemia caused by acute injury induced by Bav. However, the decrease of activity in the COX-2 pathway in the first stages of revascularization contributes to the elevated production of key pro-angiogenic mediators that up-regulate the restoration of microvasculature and blood flow in muscle tissue injured by botropic venoms.

两栖类毒液（Bav）含有金属蛋白酶，会破坏微血管系统，从而影响肌肉组织在损伤后的再生。本研究调查了环氧化酶-2（COX-2）通路对 Bav 诱发的肌肉损伤中血管损伤和血管再通的影响。向小鼠的腓肠肌注射 Bav，并在注射后 30 分钟、2 天和 6 天使用鲁米拉考昔布（一种选择性 COX-2 抑制剂）治疗。在注射后 24 小时、7 天和 21 天对肌肉组织进行分析。注射 Bav 后 24 小时，COX-2 表达下降，表明肌肉组织严重坏死和损失。Bav 注射和鲁米拉考昔布治疗都会影响前列腺素（PG）D2 和 PGE2 的产生。注射 Bav 后 7 天和 21 天，COX-2 表达增加，而 PGDs 水平不受鲁米拉考昔布的影响，这表明另一种同工酶 COX-1 途径可能有助于 PGs 的释放。经 Bav/lumiracoxib 处理的动物肢体缺血加剧，这意味着 COX-2 衍生的前列腺素可保护血管完整性。血管生成标志物 CD31 在注射 Bav 后最初（24 小时）有所下降，但在注射 Bav/lumiracoxib 后 7 天和 21 天又有所上升，这表明 COX-2 衍生的前列腺素在早期血管生成和组织再生中起到了下调作用。注射 Bav 后 7 天，血管内皮生长因子（VEGF）的生成量上升，支持其在血管生成中的作用。之前使用鲁米拉考昔布（lumiracoxib）治疗可促进巴甫损伤后 21 天血管内皮生长因子水平的释放，这表明在血管再通的早期阶段抑制 COX-2 通路可刺激血管内皮生长因子的释放，从而调节血管新生。同样，对血管重塑至关重要的金属蛋白酶（MMPs），如 MMP-9、MMP-10 和 MMP-13，也在 Bav/lumiracoxib 治疗 21 天后升高。总之，COX-2 通路对于减轻 Bav 引起的急性损伤导致的高度缺血至关重要。然而，在血管再通的最初阶段，COX-2 通路活性的降低有助于促进血管生成的关键介质的生成，从而上调受肉毒中毒损伤的肌肉组织微血管和血流的恢复。

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引用次数: 0

Dehydroepiandrosterone (DHEA), a circulating steroid hormone precursor produced potent vasorelaxation in rat aorta and mesenteric arteries through blockade of L-type voltage-dependent calcium channels 脱氢表雄酮（DHEA）是一种循环中的类固醇激素前体，通过阻断 L 型电压依赖性钙通道对大鼠主动脉和肠系膜动脉产生强效的血管舒张作用。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2024-11-04 DOI: 10.1016/j.mvr.2024.104758

Divya Mishra , Pankaj Yadav , Hina Iqbal , Shweta Parashar , Arvind Singh Negi , Debabrata Chanda

Dehydroepiandrosterone (DHEA) is known for potent cardioprotective properties and diminished DHEA level in plasma is often associated with hypertension and age-related anomalies. However, putative ex-vivo vasorelaxation potential of DHEA in systemic resistance vessels like mesenteric arteries and conduit arteries like aorta are still to be worked out. The study aimed to explore vasorelaxation potential of DHEA in superior and resistance mesenteric arteries and aorta in rats and to determine the contribution L-type Voltage dependent calcium channel (L-VDCC) in the relaxation response in these arterial tissues. Ex-vivo vasorelaxation potential of DHEA in isolated arterial tissues were evaluated and the mechanism of vasorelaxation induced by DHEA was characterized by contraction experiment in isolated arterial tissue and in-vitro calcium imaging assay using Fluo-4 in primary vascular smooth muscle cells derived from aorta. In the current study, DHEA was found to exhibit potent concentration dependent, endothelium and potassium channel independent vasorelaxation response in conduit and resistance arteries. The block of L-type VDCCs was evident from the findings that DHEA in a concentration-dependent manner inhibited both BAY K-8644 and CaCl₂-induced contractions. The results of the contraction experiment were further substantiated by Fluo-4 mediated calcium imaging assay in primary rat vascular smooth muscle wherein DHEA concentration dependently blocked noradrenaline and BAY K-8644-induced rise in intracellular calcium fluorescence. The present study showed potent endothelium and potassium channel independent vasorelaxation properties of DHEA in aorta, superior and resistance mesenteric artery mediated predominantly through blockade of L-VDCC.

众所周知，脱氢表雄酮（DHEA）具有强大的心脏保护特性，血浆中 DHEA 水平的降低通常与高血压和与年龄有关的异常有关。然而，DHEA在肠系膜动脉等全身阻力血管和主动脉等导管动脉中的体外舒张血管潜力仍有待研究。本研究旨在探索 DHEA 在大鼠肠系膜上动脉、阻力动脉和主动脉中的血管舒张潜能，并确定 L 型电压依赖性钙通道（L-VDCC）在这些动脉组织的舒张反应中的作用。研究评估了 DHEA 在离体动脉组织中的体外血管舒张潜能，并通过离体动脉组织收缩实验和体外钙成像实验（使用 Fluo-4 对来自主动脉的原发性血管平滑肌细胞进行钙成像）确定了 DHEA 诱导的血管舒张机制。目前的研究发现，DHEA 在导管动脉和阻力动脉中表现出强效的浓度依赖性、独立于内皮和钾离子通道的血管舒张反应。DHEA 以浓度依赖性方式抑制了 BAY K-8644 和 CaCl2 诱导的收缩，这证明了 L 型 VDCC 的阻断作用。原代大鼠血管平滑肌的 Fluo-4 介导的钙成像实验进一步证实了收缩实验的结果，DHEA 浓度依赖性地阻断了去甲肾上腺素和 BAY K-8644 诱导的细胞内钙荧光的上升。本研究表明，DHEA 在主动脉、肠系膜上动脉和肠系膜阻力动脉中具有强效的独立于内皮和钾通道的血管舒张特性，主要是通过阻断 L-VDCC 介导的。

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引用次数: 0

Morphometrics of polypoidal choroidal vasculopathy lesions and choroidal vascular associated with treatment response using swept-source optical coherence tomography angiography 使用扫源光学相干断层血管造影术测量多形性脉络膜血管病变的形态计量学以及与治疗反应相关的脉络膜血管。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2024-11-04 DOI: 10.1016/j.mvr.2024.104759

Yue Zhang , Jianing Wang , Zhaoxia Zheng , Shuang Song , Xiaoya Gu , Xiaobing Yu

Purpose

To evaluate quantitative metrics of neovascularization lesions and choroidal vascular using swept-source optical coherence tomography angiography (SS-OCTA) in polypoidal choroidal vasculopathy (PCV) eyes, and investigate the relationship between imaging biomarkers and treatment outcomes of intravitreal anti-vascular endothelial growth factor (VEGF).

Methods

We retrospectively recruited 56 PCV patients. Choroidal features included subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI). Quantitative metrics of neovascularization lesions included total vessel length (TVL), average vessel length (AVL), junction density (JD), total number of endpoints (TNE), and mean lacunarity (ML). We performed multivariate logistic and linear regression models to determine the prognostic factors for functional and morphological outcomes.

Results

By comparison, functional good-responders had poorer best corrected visual acuity, higher TNE, and lower ML at baseline. Morphological good-responders had higher central retinal thickness, higher TNE, lower TVL and AVL, lower ML, lower SFCT and CVI. High-shrinkage of vessel area subgroup had higher JD and TNE, lower TVL and AVL, lower ML, lower SFCT and CVI. Multivariate analysis showed good morphological response was correlated with lower SFCT (P < 0.01). High-shrinkage subgroup was correlated with lower AVL (P = 0.017) and higher TNE (P < 0.01).

Conclusion

Quantitative metrics of neovascularization lesions and choroidal characteristics using SS-OCTA had the potential to be imaging biomarkers for predicting the response to anti-VEGF treatment. PCV lesions with higher TNE and lower AVL tended to appear higher shrinkage of vessel area, and lower SFCT was correlated with good morphological response.

目的：使用扫源光学相干断层血管成像（SS-OCTA）评估多形性脉络膜血管病（PCV）眼部新生血管病变和脉络膜血管的定量指标，并研究成像生物标志物与玻璃体内抗血管内皮生长因子（VEGF）治疗效果之间的关系：我们回顾性招募了 56 名 PCV 患者。脉络膜特征包括眼底脉络膜厚度（SFCT）和脉络膜血管指数（CVI）。新生血管病变的定量指标包括血管总长度（TVL）、平均血管长度（AVL）、交界密度（JD）、终点总数（TNE）和平均裂隙度（ML）。我们建立了多变量逻辑和线性回归模型，以确定功能和形态学结果的预后因素：结果：相比之下，功能良好反应者基线最佳矫正视力较差，TNE较高，ML较低。形态学良好反应者视网膜中央厚度较高、TNE较高、TVL和AVL较低、ML较低、SFCT和CVI较低。血管面积高度收缩亚组的 JD 和 TNE 较高，TVL 和 AVL 较低，ML 较低，SFCT 和 CVI 较低。多变量分析显示，良好的形态学反应与较低的 SFCT 相关（P 结语）：使用 SS-OCTA 对新生血管病变和脉络膜特征进行定量测量，有可能成为预测抗血管内皮生长因子治疗反应的成像生物标志物。TNE较高和AVL较低的PCV病变往往会出现较高的血管面积收缩，而较低的SFCT与良好的形态学反应相关。

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引用次数: 0