Microvascular research最新文献_第4页

Clinical profile and long-term outcomes of chest pain patients with coronary microvascular dysfunction from the emergency department – results from the Yale-CMD registry 急诊科胸痛合并冠状动脉微血管功能障碍患者的临床特征和长期预后——来自耶鲁- cmd注册表的结果

IF 2.7 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-10-17 DOI: 10.1016/j.mvr.2025.104878

Basmah Safdar , Bin Zhou , Fangyong Li , Paolo G. Camici , James Dziura , Ania M. Jastreboff , Alexandra Lansky , Samit M. Shah , Albert Sinusas , Erica Spatz , Gail D'Onofrio

Objective

To investigate the long-term prognosis of coronary microvascular dysfunction (CMD) in emergency department (ED) patients with chest pain for major adverse cardiac events (MACE) due to all-cause mortality, myocardial infarction (MI), heart failure (HF), or stroke.

Methods

A prospective cohort of ED patients evaluated by hybrid cardiac positron emission tomography with attenuation computed tomography within 24 h of arrival. Patients were classified as: (1) Controls – coronary flow reserve (CFR) ≥2 without perfusion defect or coronary calcification; (2) CMD: CFR <2 without defect or calcification; or (3) CAD/CALC – established or new coronary artery disease (CAD) or calcification (CALC). We conducted annual follow-ups for MACE and all-cause healthcare utilization (hospitalizations and ED visits). We adjusted incidence rates (aIR) and hazard ratio (aHR) for demographics, comorbidities, and medications.

Results

Between 2014 and 2020, 189 patients were enrolled: 95 (50 %) Controls, 34 (18 %) with CMD, and 60 (32 %) with CAD/CALC. Median follow-up time was 50 months (38–92), and a total of 187 unique MACE were recorded in 44 patients. CMD patients had 4× higher MACE risk than controls (aIR 3.8; 95 % CI: 2.1–6.6). CAD/CALC patients had similarly higher risk than controls (aIR: 4.5; 95 % CI: 2.6–7.8). CMD patients had 4× higher risk for time to first MACE than controls (aHR: 3.6; 95 % CI: 1.2–10.7) and higher healthcare utilization per 100 person-months (aIR: 124; 95 % CI: 119–130). Using Seattle Angina Questionnaire, CMD patients showed worse angina frequency than controls (difference: -16.4, 95 % CI: −29.5 to −3.4).

Conclusions

Patients with contemporary phenotypes of ischemia (CMD and CAD/CALC) had higher adverse events than controls, positing ED encounters as an opportunity for early identification and treatment.

目的：探讨急诊科（ED）胸痛患者冠状动脉微血管功能障碍（CMD）的长期预后，这些患者的主要不良心脏事件（MACE）是由全因死亡、心肌梗死（MI）、心力衰竭（HF）或脑卒中引起的。方法：对ED患者进行前瞻性队列研究，在24 h内通过混合心脏正电子发射断层扫描和衰减计算机断层扫描进行评估。患者分为：(1)对照组-冠状动脉血流储备(CFR)≥2，无灌注缺损或冠状动脉钙化；(2) CMD: CFR结果：2014 - 2020年间，189例患者入组：对照组95例（50 %），CMD组34例（18 %），CAD/CALC组60例（32 %）。中位随访时间为50 个月（38-92），44例患者共记录187次MACE。CMD患者的MACE风险比对照组高4倍（aIR 3.8; 95 % CI: 2.1-6.6）。CAD/CALC患者的风险同样高于对照组（aIR: 4.5; 95 % CI: 2.6-7.8）。CMD患者发生首次MACE的时间风险比对照组高4倍（aHR: 3.6; 95 % CI: 1.2-10.7），医疗保健利用率更高（aIR: 124; 95 % CI: 119-130）。使用西雅图心绞痛问卷，CMD患者心绞痛发生率较对照组差（差异：-16.4,95 % CI: -29.5 ~ -3.4, p = 0.01）。结论：当代缺血表型（CMD和CAD/CALC）的患者比对照组有更高的不良事件，假设ED遭遇是早期识别和治疗的机会。

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引用次数: 0

The association between cutaneous microvascular dysfunction and pulmonary artery hemodynamics in heart transplant candidates 心脏移植候选者皮肤微血管功能障碍与肺动脉血流动力学之间的关系

IF 2.7 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-10-01 DOI: 10.1016/j.mvr.2025.104877

Antonio Feliciano Fatorelli , Eduardo Tibirica , Daniel Arthur Barata Kasal

引用次数: 0

Association between posterior vitreous detachment stage and quantitative neovascularization morphology in proliferative diabetic retinopathy using wide-field swept-source optical coherence tomography angiography 增生性糖尿病视网膜病变后玻璃体脱离阶段与定量新生血管形态的关系。

IF 2.7 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-09-19 DOI: 10.1016/j.mvr.2025.104875

Zikang Xu , Ruoyu Chen , Jing Li , Danling Huang , Taozheng Li , Huilin Liang , Zhicong Xu , Jiayi Huang , Mi Gui , I.M. Hojas , Xuenan Zhuang , Liang Zhang

Purpose

To investigate the association between posterior vitreous detachment (PVD) and the progression of proliferative diabetic retinopathy (PDR) by analyzing the morphological evolution of neovascularization (NV) across PVD stages using swept-source optical coherence tomography angiography (SS-OCTA).

Methods

This retrospective study assessed PVD stages via SS-OCT. Quantitative analysis of SS-OCTA images was performed with ImageJ and AngioTool to extract NV morphological features including perimeter, MaxFeret, MiniFeret, Feret ratio (FR), maximum vessel caliber, vessel dispersion, fractal dimension index (FDI), vessel area (VA), vessel density, total vessel length (TVL), average vessel length (AVL), total number of junctions (TNJ), junction density (JD), total number of endpoints, endpoint density (ED), and mean lacunarity (MEL) to assess NV size, activity, and complexity. Analysis of NV morphology and PVD association via Generalized Linear Mixed Model.

Results

Significant differences (P < 0.05) in multiple NV parameters were observed across PVD stages in the 74 included eyes. At stage 4, most parameters reached their minima, except for JD and ED, which peaked. Trend analysis revealed inverted U-shaped trajectories for size (perimeter, MaxFeret, MiniFeret, VA), activity (TNJ, TVL, AVL), and complexity (FDI) parameters with PVD progression. In contrast, JD and ED followed U-shaped trends. All inflection points clustered between stages 1 and 2.

Conclusions

NV morphology in PDR evolves systematically from a highly intricate and extensive structure in early PVD (Stage 1 or 2) to a simplified and localized architecture in stage 4. Concomitant alterations in NV activity and complexity likely occur, providing morphological insights into PVD's role in PDR.

目的：通过扫描源光学相干断层扫描血管造影（SS-OCTA）分析PVD分期新生血管（NV）的形态学演变，探讨玻璃体后脱离（PVD）与增生性糖尿病视网膜病变（PDR）进展之间的关系。方法：本回顾性研究通过SS-OCT评估PVD分期。使用ImageJ和AngioTool对SS-OCTA图像进行定量分析，提取NV形态学特征，包括周长、MaxFeret、MiniFeret、Feret比率（FR）、最大血管直径、血管离散度、分形维指数（FDI）、血管面积（VA）、血管密度、血管总长度（TVL）、血管平均长度（AVL）、总结数（TNJ）、结密度（JD）、总端点数、端点密度（ED）和平均间隙度（MEL），以评估NV大小。活动和复杂性。广义线性混合模型分析NV形态与PVD关联。结果：显著差异(P 结论：PDR的NV形态系统地从早期PVD（1或2期）的高度复杂和广泛的结构演变为4期的简化和局部结构。同时可能发生NV活性和复杂性的改变，这为PVD在PDR中的作用提供了形态学上的见解。

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引用次数: 0

Involvement of monocarboxylate transporter 7 in taurine efflux transport from rat retinal pericytes and capillary endothelial cells 单羧酸转运蛋白7参与大鼠视网膜周细胞和毛细血管内皮细胞的牛磺酸外排运输。

IF 2.7 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-09-18 DOI: 10.1016/j.mvr.2025.104876

Yuma Tega , Fuki Kusakabe , Shin-ichi Akanuma , Ken-ichi Hosoya

Purpose

Taurine exists abundantly in the retina and plays a vital role in retinal function. Monocarboxylate transporter 7 (MCT7) is found as a facilitative taurine transporter; however, its involvement in taurine dynamics in the retina is not yet fully understood. The purpose of the present study is to clarify the protein expression and function of MCT7 in retinal cells.

Methods

Guinea pig antibodies were raised against the amino acid residues of rat MCT7, and immunostaining was performed to clarify protein expression in the rat retina. To characterize taurine influx into retinal pericytes, a [³H]taurine transport assay was conducted using TR-rPCT1 cells, immortalized rat retinal pericytes. A knockdown assay using MCT7 small interfering RNA (siRNA) was performed to examine the involvement of MCT7 in taurine efflux in TR-rPCT1 and immortalized rat retinal capillary endothelial (TR-iBRB2) cells.

Results

The MCT7 protein expression was observed throughout the retinal layer. Immunostaining of isolated retinal capillaries revealed MCT7 expression in retinal pericytes and capillary endothelial cells. [³H]Taurine influx transport in TR-rPCT1 cells depends on temperature, concentration (K_m = 11.2 μM), and extracellular Na⁺ and Cl⁻, and was inhibited by substrates for taurine transporter (TauT), suggesting the involvement of TauT in taurine influx in retinal pericytes. Moreover, MCT7 siRNA decreased MCT7 expression and [³H]taurine efflux in TR-rPCT1 and TR-iBRB2 cells, suggesting that the taurine efflux transport involves MCT7 at least partly.

Conclusions

The present study revealed that MCT7 functions as a taurine efflux transporter in both retinal pericytes and capillary endothelial cells.

目的：牛磺酸在视网膜中大量存在，对视网膜功能起着至关重要的作用。单羧酸转运蛋白7 （MCT7）是一种促进性牛磺酸转运蛋白；然而，它对视网膜中牛磺酸动力学的参与尚未完全了解。本研究的目的是阐明MCT7在视网膜细胞中的蛋白表达和功能。方法：培养针对大鼠MCT7氨基酸残基的豚鼠抗体，并进行免疫染色以澄清大鼠视网膜中的蛋白表达。为了描述牛磺酸向视网膜周细胞内流的特征，使用TR-rPCT1细胞（永生化大鼠视网膜周细胞）进行了[3H]牛磺酸运输试验。使用MCT7小干扰RNA （siRNA）进行敲低实验，以检测MCT7在TR-rPCT1和永生化大鼠视网膜毛细血管内皮细胞（TR-iBRB2）中牛磺酸外排的参与。结果：MCT7蛋白在视网膜全层均有表达。分离的视网膜毛细血管免疫染色显示MCT7在视网膜周细胞和毛细血管内皮细胞中表达。[3H] TR-rPCT1细胞的牛磺酸内流转运受温度、浓度（Km = 11.2 μM）和细胞外Na+和Cl-的影响，并被牛磺酸转运蛋白（taaut）底物抑制，提示taaut参与了视网膜周细胞的牛磺酸内流。此外，MCT7 siRNA降低了TR-rPCT1和TR-iBRB2细胞中MCT7的表达和[3H]牛磺酸外排，表明牛磺酸外排运输至少部分涉及MCT7。结论：本研究表明MCT7在视网膜周细胞和毛细血管内皮细胞中均作为牛磺酸外排转运体起作用。

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引用次数: 0

Nailfold video capillaroscopy predicts severe progression at three years in systemic sclerosis: Results from SCLEROCAP study 甲襞视频毛细血管镜可预测系统性硬化症三年后的严重进展：来自clerocap研究的结果。

IF 2.7 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-09-16 DOI: 10.1016/j.mvr.2025.104874

Carine Boulon , Iban Larrouture , Sophie Blaise , Marion Mangin , Joëlle Decamps-Le Chevoir , Patricia Senet , Isabelle Lazareth , Nathalie Baudot , Laurent Tribout , Bernard Imbert , François-Xavier Lapébie , Philippe Lacroix , Marie-Elise Truchetet , Julien Seneschal , Anna Solanilla , Estibaliz Lazaro , Isabelle Quéré , Marc-Antoine Pistorius , Claire Le Hello , Edouard Lhomme , Joël Constans

Objectives

Systemic sclerosis (SSc) has a variable evolution but may be life-threatening owing to pulmonary, cardiac or renal involvement. Nailfold video capillaroscopy (NVC) is abnormal early in the disease and is crucial for diagnosis. An association between subtypes of scleroderma pattern and disease progression has been suggested. Therefore, we conducted a prospective study to assess whether capillaroscopy can identify SSc patients at risk of progression.

Methods

SCLEROCAP was a prospective multicentre observational study that included patients with a diagnosis of SSc followed up for three years. Each patient had yearly standard evaluation and NVC. Images were read by two observers blinded from each other and were classified into subtypes (2 for Maricq's and 3 for Cutolo's classification). Severe progression was defined as cardiac, pulmonary or renal involvement or progression and was assessed by a validation committee.

Results

Three hundred and eighty-seven patients were included of whom 369 were followed-up and 53 (14 %) had severe progression. A simple model using Cutolo's capillaroscopic late stage, short duration of disease and age was as powerful in predicting severe progression as a model using all the parameters known to be predictive (AUC[95 %CI] 0.74[0.67–0.82] vs 0.73[0.64–0.77] respectively.

Conclusion

NVC is a predictor of severe progression and might be helpful for early therapeutic decisions in patients with SSc.

目的：系统性硬化症（SSc）有一个可变的演变，但可能危及生命，由于肺，心脏或肾脏受累。甲襞视频毛细血管镜检查（NVC）在疾病早期异常，对诊断至关重要。已提出硬皮病亚型模式与疾病进展之间的关联。因此，我们进行了一项前瞻性研究，以评估毛细管镜检查是否可以识别有进展风险的SSc患者。方法：scclerocap是一项前瞻性多中心观察性研究，纳入了诊断为SSc的患者，随访三年。每位患者每年进行标准评估和NVC。图像由两名相互盲视的观察者阅读，并分为亚型（Maricq分类为2，Cutolo分类为3）。严重进展定义为心脏、肺或肾脏受累或进展，并由验证委员会评估。结果：共纳入387例患者，随访369例，病情严重进展53例（14% %）。使用Cutolo毛细管镜的简单模型预测晚期、疾病持续时间短和年龄与使用所有已知预测参数的模型一样有效（AUC[95 %CI] 0.74[0.67-0.82] vs 0.73[0.64-0.77]）。结论：NVC是严重进展的预测因子，可能有助于SSc患者的早期治疗决策。

{"title":"Nailfold video capillaroscopy predicts severe progression at three years in systemic sclerosis: Results from SCLEROCAP study","authors":"Carine Boulon , Iban Larrouture , Sophie Blaise , Marion Mangin , Joëlle Decamps-Le Chevoir , Patricia Senet , Isabelle Lazareth , Nathalie Baudot , Laurent Tribout , Bernard Imbert , François-Xavier Lapébie , Philippe Lacroix , Marie-Elise Truchetet , Julien Seneschal , Anna Solanilla , Estibaliz Lazaro , Isabelle Quéré , Marc-Antoine Pistorius , Claire Le Hello , Edouard Lhomme , Joël Constans","doi":"10.1016/j.mvr.2025.104874","DOIUrl":"10.1016/j.mvr.2025.104874","url":null,"abstract":"<div><h3>Objectives</h3><div>Systemic sclerosis (SSc) has a variable evolution but may be life-threatening owing to pulmonary, cardiac or renal involvement. Nailfold video capillaroscopy (NVC) is abnormal early in the disease and is crucial for diagnosis. An association between subtypes of scleroderma pattern and disease progression has been suggested. Therefore, we conducted a prospective study to assess whether capillaroscopy can identify SSc patients at risk of progression.</div></div><div><h3>Methods</h3><div>SCLEROCAP was a prospective multicentre observational study that included patients with a diagnosis of SSc followed up for three years. Each patient had yearly standard evaluation and NVC. Images were read by two observers blinded from each other and were classified into subtypes (2 for Maricq's and 3 for Cutolo's classification). Severe progression was defined as cardiac, pulmonary or renal involvement or progression and was assessed by a validation committee.</div></div><div><h3>Results</h3><div>Three hundred and eighty-seven patients were included of whom 369 were followed-up and 53 (14 %) had severe progression. A simple model using Cutolo's capillaroscopic late stage, short duration of disease and age was as powerful in predicting severe progression as a model using all the parameters known to be predictive (AUC[95 %CI] 0.74[0.67–0.82] vs 0.73[0.64–0.77] respectively.</div></div><div><h3>Conclusion</h3><div>NVC is a predictor of severe progression and might be helpful for early therapeutic decisions in patients with SSc.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"163 ","pages":"Article 104874"},"PeriodicalIF":2.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086385","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

Retinal neurodegeneration and choroidal changes of early diabetes in peripapillary region detected by swept-source optical coherence tomography angiography 扫描源光学相干断层血管造影检测早期糖尿病乳头周围区视网膜神经变性和脉络膜改变

IF 2.7 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-09-10 DOI: 10.1016/j.mvr.2025.104867

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

Purpose

This study was designed to evaluate peripapillary retinal nerve fiber layer (pRNFL) and choroidal alterations in diabetic patients without diabetic retinopathy (NDR), and further explore their association utilizing ultrawide-field swept-source optical coherence tomography angiography (UWF-SS-OCTA).

Methods

This cross-sectional study included 169 eyes of 169 NDR subjects and 54 eyes of 54 healthy controls. pRNFL, choroidal thickness and volume were compared and measured with UWF-SS-OCTA. The association between pRNFL and choroidal parameters was assessed with Spearman correlation analysis. Further multivariate linear regression analysis was performed to evaluate their relationship after adjusting for confounding factors.

Results

Compared with healthy controls, NDR patients showed reduced choroidal thickness and volume in the full range and several peripapillary subfields, while a statistical decrease of pRNFL was only detected in the inferior quadrant (P = 0.04). Regarding the distribution profiles in the peripapillary region, the choroid was thickest in the temporal region and thinnest in the inferior region, and a more prominent decrease compared with controls was found in the inferior region. Average pRNFL thickness was independently associated with full-range mean choroidal volume in multiple regression analysis (β = 0.16, P = 0.04).

Conclusion

As two early signs of DR, choroidal thinning could precede retinal neurodegeneration. Decreased choroidal thickness may account for the susceptibility of RNFL thinning.

目的评价无糖尿病视网膜病变（NDR）的糖尿病患者乳头周围视网膜神经纤维层（pRNFL）和脉络膜改变，并利用超宽视场扫描源光学相干断层血管造影（UWF-SS-OCTA）进一步探讨两者之间的相关性。方法横断面研究包括169例NDR患者的169只眼和54例健康对照者的54只眼。用UWF-SS-OCTA比较测定pRNFL、脉络膜厚度和体积。采用Spearman相关分析评估pRNFL与脉络膜参数的关系。在调整混杂因素后，进一步进行多元线性回归分析来评估两者之间的关系。结果与健康对照组相比，NDR患者全范围及多个乳头周围亚野的脉络膜厚度和体积均减少，pRNFL仅在下象限有统计学意义上的减少（P = 0.04）。在乳头周围区域的分布剖面上，颞区脉络膜最厚，下区最薄，下区与对照组相比减少更为明显。在多元回归分析中，平均pRNFL厚度与全范围平均脉络膜体积独立相关（β = 0.16, P = 0.04）。结论脉络膜变薄是视网膜神经退行性变的两个早期征象。脉络膜厚度减少可能是RNFL变薄的原因。

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引用次数: 0

Sex differences in near-infrared spectroscopy reactive hyperemia: Influence of adipose tissue and desaturation rate 近红外光谱反应性充血的性别差异：脂肪组织和去饱和率的影响。

IF 2.7 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-09-07 DOI: 10.1016/j.mvr.2025.104865

Matthew A. Chatlaong , Hannah C. Dowell , Orlandria J. Smith , Matthew B. Jessee

Sex differences in near-infrared spectroscopy (NIRS) reactive hyperemia outcomes have been previously reported, with females generally having a lower reperfusion slope. Sex differences have also been reported for adipose tissue thickness (ATT), which affects the NIRS signal, and desaturation during occlusion, which may act on reperfusion slopes. We aimed to compare statistically adjusted and unadjusted sex differences in reperfusion slope during reactive hyperemia.

Methods

23 female and 22 male participants completed forearm and thigh vascular occlusion tests. ATT was measured via ultrasound. Reperfusion slopes (StO₂%/s) were compared between sexes using linear models with and without desaturation slope (StO₂%/s) and ATT as covariates. Results are mean or mean difference [95 % CI].

Results

In both limbs, females had greater ATT (p < 0.001). Desaturation rate was lower in females for the leg (−0.02 [−0.03, −0.01]), but not the arm (0.00 [−0.01, 0.02]). Unadjusted, males had greater reperfusion slope in the leg (females = 0.91 [0.70, 1.11], males = 1.59 [1.33, 1.85], p < 0.001) but not the arm (females = 1.60 [1.36, 1.84], males = 1.57 [1.29, 1.86], p = 0.874). Sex differences were not observed in adjusted models (both p ≥ 0.631). ATT and desaturation slope explained unique variance in the leg (both p ≤ 0.001), but only desaturation slope did in the arm (p < 0.001).

Conclusion

Sex differences may have been related to differing ATT and desaturation rates. Researchers may consider adjusting for ATT and/or desaturation rate when estimating sex differences with NIRS reactive hyperemia.

近红外光谱（NIRS）反应性充血结果的性别差异先前有报道，女性通常具有较低的再灌注斜率。性别差异也被报道为脂肪组织厚度（ATT），影响近红外光谱信号，和闭塞期间的去饱和，这可能对再灌注斜率起作用。我们的目的是比较反应性充血期间经统计学校正和未经统计学校正的再灌注斜率的性别差异。方法：23名女性和22名男性受试者完成前臂和大腿血管闭塞试验。超声测量ATT。采用带和不带去饱和斜率（StO2%/s）和ATT作为协变量的线性模型比较两性间的再灌注斜率（StO2%/s）。结果为平均或平均差异[95 % CI]。结论：性别差异可能与不同的ATT和去饱和率有关。在估计近红外反应性充血的性别差异时，研究人员可能会考虑调整ATT和/或去饱和率。

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引用次数: 0

Histamine induces vascular endothelial cell proliferation via the histamine H1 receptor–extracellular regulated protein kinase 1/2–cyclin D1/cyclin-dependent kinase 4/6 axis 组胺通过组胺H1受体-细胞外调节蛋白激酶1/2-cyclin D1/cyclin依赖性激酶4/6轴诱导血管内皮细胞增殖。

IF 2.7 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-09-03 DOI: 10.1016/j.mvr.2025.104866

Hidenori Wake , Omer Faruk Hatipoglu , Takashi Nishinaka , Masahiro Watanabe , Takao Toyomura , Shuji Mori , Masahiro Nishibori , Hideo Takahashi

Histamine is a biogenic amine that plays important roles in the inflammatory phase of physiological wound healing and proliferation of normal and tumor cells. Stimulation of the histamine H1 receptor induces vascular endothelial cell proliferation, possibly contributing to angiogenesis during wound healing and cancer development. However, the specific signaling pathways involved in angiogenesis remain unclear. Based on our previous report that histamine induces endothelial cell tube formation by increasing the vascular endothelial growth factor and matrix metalloproteinase levels via the H1 receptor, we aimed to further examine histamine-induced cell proliferation using EA.hy926 vascular endothelial cells in this study. Histamine phosphorylated extracellular regulated protein kinase-1/2 through the protein kinase C pathway via the H1 receptor and increased c-Fos expression via phosphorylation of Elk-1 and CRE-binding protein. Moreover, c-Fos formed activator protein-1, which further upregulated cyclin D1 expression. Cyclin D1 formed a complex with cyclin-dependent kinase-4/6 and phosphorylated Rb, causing the transcription factor E2F, which is bound to Rb, to dissociate from Rb and induce the factors important for S phase initiation that advance the cell cycle. Overall, our findings in this study to identify H1 receptor-mediated cell proliferation signals in endothelial cells using histamine can aid in the development of new strategies for wound healing and cancer treatment.

组胺是一种生物胺，在生理创伤愈合和正常及肿瘤细胞增殖的炎症期起重要作用。组胺H1受体的刺激诱导血管内皮细胞增殖，可能在伤口愈合和癌症发展过程中促进血管生成。然而，参与血管生成的具体信号通路仍不清楚。基于我们之前的报道，组胺通过H1受体增加血管内皮生长因子和基质金属蛋白酶水平，诱导内皮细胞形成管，本研究旨在进一步研究组胺诱导血管内皮细胞增殖的EA.hy926。组胺通过H1受体通过蛋白激酶C途径磷酸化细胞外调节蛋白激酶1/2，并通过磷酸化Elk-1和cre结合蛋白增加C - fos表达。此外，c-Fos形成激活蛋白1，进一步上调cyclin D1的表达。Cyclin D1与Cyclin依赖性激酶4/6形成复合物，磷酸化Rb，使与Rb结合的转录因子E2F与Rb分离，诱导S期起始的重要因子提前细胞周期。总的来说，我们在这项研究中发现，利用组胺识别内皮细胞中H1受体介导的细胞增殖信号，有助于开发伤口愈合和癌症治疗的新策略。

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引用次数: 0

Shear stress-activated MMP-2 promotes BMSCs migration via the LIMK1/Cofilin axis during vascular remodeling 剪切应力激活的MMP-2在血管重塑过程中通过LIMK1/Cofilin轴促进骨髓间充质干细胞迁移

IF 2.7 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-08-27 DOI: 10.1016/j.mvr.2025.104863

Yuan Liang , Jianjin Wu , Xingjian Fang , Yan Chang , Yumei Tang , Guangliang Diao , Cunping Yin

Shear stress enhances matrix metalloproteinase-2 (MMP-2) expression, which plays a critical role in bone marrow mesenchymal stem cells (BMSCs) migration and vascular remodeling via microenvironmental interactions with mouse aortic endothelial cells (MAECs). MAECs were exposed to disturbed flow using a custom flow device for 1, 3, or 5 h, and conditioned media (MAEC-CM) were collected. BMSCs migration in response to different MAEC-CM conditions was assessed by flow cytometry, transwell, and wound-healing assays. MMP-2 levels in MAEC-CM were modulated with recombinant protein or neutralizing antibody. LIMK1/Cofilin pathway activation was evaluated by western blot, and the LIMK1 inhibitor BMS-3 was used to confirm pathway function. Disturbed flow altered MAECs density, morphology, and intercellular gaps, with apoptosis increasing over time. ELISA showed MMP-2 secretion peaked at 3 h, coinciding with maximal BMSCs migration. Recombinant MMP-2 (400 ng/mL) further enhanced, while MMP-2 neutralizing antibody (100 ng/mL) suppressed, migration induced by MAEC-CM-3 h. Western blot revealed significant phosphorylation of LIMK1 and Cofilin after MAEC-CM-3 h treatment, with higher levels in recombinant MMP-2–treated groups compared to neutralization. BMS-3 significantly reduced MMP-2–induced BMSCs migration and phosphorylation of LIMK1/Cofilin without affecting total protein levels. These results indicate that shear stress–induced MMP-2 promotes BMSCs motility through LIMK1-dependent Cofilin activation. This study not only clarifies the molecular mechanism by which disturbed flow regulates BMSCs migration but also provides a theoretical basis for BMSC-mediated vascular repair, offering potential targets for future clinical applications.

剪切应力增强基质金属蛋白酶-2 （MMP-2）的表达，MMP-2通过与小鼠主动脉内皮细胞（MAECs）的微环境相互作用在骨髓间充质干细胞（BMSCs）迁移和血管重构中起关键作用。使用定制的流动装置将maec暴露于扰动流中1,3或5小时，并收集条件介质（MAEC-CM）。通过流式细胞术、transwell和伤口愈合试验评估骨髓间充质干细胞对不同MAEC-CM条件的迁移。用重组蛋白或中和抗体调节MAEC-CM的MMP-2水平。western blot检测LIMK1/Cofilin通路激活情况，用LIMK1抑制剂BMS-3检测该通路功能。紊乱的血流改变了maec的密度、形态和细胞间隙，随着时间的推移，细胞凋亡增加。ELISA结果显示，MMP-2分泌在3 h达到峰值，与骨髓间充质干细胞最大迁移时间一致。重组MMP-2 （400 ng/mL）进一步增强，而MMP-2中和抗体（100 ng/mL）抑制MAEC-CM-3 h诱导的迁移。Western blot显示，MAEC-CM-3 h后，重组MMP-2处理组的LIMK1和Cofilin磷酸化水平高于中和组。BMS-3显著降低mmp -2诱导的骨髓间充质干细胞迁移和LIMK1/Cofilin磷酸化，但不影响总蛋白水平。这些结果表明，剪切应力诱导的MMP-2通过limk1依赖性的Cofilin激活促进骨髓间充质干细胞的运动。本研究不仅阐明了血流紊乱调节骨髓间充质干细胞迁移的分子机制，也为骨髓间充质干细胞介导的血管修复提供了理论基础，为今后的临床应用提供了潜在靶点。

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引用次数: 0

Pilot study on near-infrared spectroscopy in peripheral artery disease: Differentiating upper and lower limbs and its correlation with the ankle-brachial index 近红外光谱在外周动脉疾病中的初步研究：上肢和下肢的鉴别及其与踝肱指数的相关性

IF 2.7 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2025-08-21 DOI: 10.1016/j.mvr.2025.104864

Jéssica Braga Amorim , Marina Dias Neto , Sandra Magalhães , António S. Barros

Peripheral artery disease (PAD) is a global health challenge, with current diagnostic methods, including the ankle-brachial index (ABI), having limitations, particularly in patients with arterial calcification. Near-infrared spectroscopy (NIRS) offers potential advantages as a non-invasive assessment tool, yet its clinical utility in PAD remains underexplored. This pilot study evaluated NIRS for differentiating between non-ischemic upper limbs and ischemic lower limbs, and assessed NIRS correlation with ABI. To do that, we performed an observational, cross-sectional study employing a convenience sample of 51 patients with PAD attending the vascular surgery outpatient clinic. A portable spectrometer recorded NIRS measurements from the right thumb and both halluces at rest. Random Forest classification was implemented to differentiate upper and lower limbs, revealing distinct NIRS patterns between upper and lower limbs, with an area under the ROC curve of 0.91 (95 % CI 0.88–0.94). Interval Partial Least Squares regression (iPLS) identified wavelength regions correlating with ABI, with the 1429–1463 nm interval being the most informative for ABI prediction, with a modest correlation (R² = 0.167, RMSECV = 0.186).

NIRS demonstrated strong discriminative capability between non-ischemic upper and ischemic lower limbs in PAD. While the correlation between NIRS and ABI was modest, it suggests potential clinical relevance. These findings indicate that NIRS could be a rapid, portable, non-invasive complementary tool for PAD assessment.

外周动脉疾病（PAD）是一个全球性的健康挑战，目前的诊断方法，包括踝肱指数（ABI），具有局限性，特别是在动脉钙化患者中。近红外光谱（NIRS）作为一种非侵入性评估工具具有潜在的优势，但其在PAD中的临床应用仍未得到充分探索。本初步研究评估了NIRS用于区分非缺血上肢和缺血下肢，并评估了NIRS与ABI的相关性。为了做到这一点，我们进行了一项观察性横断面研究，采用51例在血管外科门诊就诊的PAD患者作为方便样本。一台便携式光谱仪记录了右拇指和两个幻觉在休息时的近红外光谱测量值。采用随机森林分类对上肢和下肢进行区分，上肢和下肢的NIRS模式明显，ROC曲线下面积为0.91 （95% CI 0.88-0.94）。区间偏最小二乘回归（iPLS）确定了与ABI相关的波长区域，其中1429-1463 nm区间对ABI预测的信息最丰富，相关性不大（R2 = 0.167, RMSECV = 0.186）。近红外光谱对非缺血性上肢和缺血性下肢有较强的区分能力。虽然NIRS和ABI之间的相关性不大，但它表明了潜在的临床相关性。这些发现表明，近红外光谱可能是一种快速、便携、无创的PAD评估补充工具。

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引用次数: 0