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Anxiety is associated with coronary microvascular dysfunction: Results from the CAMADA study 焦虑与冠状动脉微血管功能障碍有关:来自CAMADA研究的结果
IF 2.4 4区 医学 Q2 Medicine Pub Date : 2023-01-12 DOI: 10.1111/micc.12798
Ying Li, Weixian Xu, Lijun Guo

Objective

Coronary microvascular dysfunction (CMD) is an important component of ischemic heart disease. Here, we assessed the associations between anxiety/depression and CMD using coronary microvascular function indicators.

Methods

The study included 81 patients (26 males and 55 females) with nonobstructive coronary artery disease. The symptoms of anxiety and depression were measured with Self-rating Anxiety Scale and Self-rating Depression Scale. Coronary microvascular function was assessed using coronary flow reserve (CFR) measured by transthoracic Doppler echocardiography.

Results

The anxiety group had significantly lower CFR than that in the no-anxiety group (2.97 ± 0.63 vs. 3.40 ± 0.61, p = .029). In bivariate correlation analysis, anxiety was negatively associated with CFR (r = −.333, p = .002). In the multiple linear regression model, after adjusting for age, sex, BMI, hypertension, dyslipidemia, smoking status, and family history of premature coronary heart disease, anxiety was negatively associated with CFR (β = −.314, p = .008). When both anxiety and depression were included in the multiple linear regression model, anxiety was also negatively associated with CFR (β = −.345, p = .012).

Conclusion

Anxiety patients had lower CFR, anxiety was independently associated with CFR. Psychological disorders may play an important role in coronary microvascular dysfunction.

目的冠状动脉微血管功能障碍是缺血性心脏病的重要组成部分。在这里,我们使用冠状动脉微血管功能指标评估焦虑/抑郁与CMD之间的关系。方法纳入非阻塞性冠状动脉疾病患者81例(男26例,女55例)。采用焦虑自评量表和抑郁自评量表对焦虑和抑郁症状进行测量。采用经胸多普勒超声心动图测量冠状动脉血流储备(CFR)评价冠状动脉微血管功能。结果焦虑组CFR明显低于无焦虑组(2.97±0.63∶3.40±0.61,p = 0.029)。在双变量相关分析中,焦虑与CFR呈负相关(r = -)。333, p = .002)。在多元线性回归模型中,在调整了年龄、性别、BMI、高血压、血脂异常、吸烟状况和早发冠心病家族史等因素后,焦虑与CFR呈负相关(β =−)。314, p = .008)。当多元线性回归模型中同时包含焦虑和抑郁时,焦虑也与CFR呈负相关(β =−)。345, p = .012)。结论焦虑患者CFR较低,焦虑与CFR独立相关。心理障碍可能在冠状动脉微血管功能障碍中起重要作用。
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引用次数: 1
Statistical and topological summaries aid disease detection for segmented retinal vascular images 统计和拓扑总结有助于疾病检测的分割视网膜血管图像
IF 2.4 4区 医学 Q2 Medicine Pub Date : 2023-01-12 DOI: 10.1111/micc.12799
John T. Nardini, Charles W. J. Pugh, Helen M. Byrne

Objective

Disease complications can alter vascular network morphology and disrupt tissue functioning. Microvascular diseases of the retina are assessed by visual inspection of retinal images, but this can be challenging when diseases exhibit silent symptoms or patients cannot attend in-person meetings. We examine the performance of machine learning algorithms in detecting microvascular disease when trained on statistical and topological summaries of segmented retinal vascular images.

Methods

We compute 13 separate descriptor vectors (5 statistical, 8 topological) to summarize the morphology of retinal vessel segmentation images and train support vector machines to predict each image's disease classification from the summary vectors. We assess the performance of each descriptor vector, using five-fold cross validation to estimate their accuracy. We apply these methods to four datasets that were assembled from four existing data repositories; three datasets contain segmented retinal vascular images from one of the repositories, whereas the fourth “All” dataset combines images from four repositories.

Results

Among the 13 total descriptor vectors considered, either a statistical Box-counting descriptor vector or a topological Flooding descriptor vector achieves the highest accuracy levels. On the combined “All” dataset, the Box-counting vector outperforms all other descriptors, including the topological Flooding vector which is sensitive to differences in the annotation styles between the different datasets.

Conclusion

Our work represents a first step to establishing which computational methods are most suitable for identifying microvascular disease and assessing their current limitations. These methods could be incorporated into automated disease assessment tools.

目的疾病并发症可改变血管网络形态,破坏组织功能。视网膜微血管疾病是通过视网膜图像的视觉检查来评估的,但当疾病表现出沉默的症状或患者不能参加面对面的会议时,这可能是具有挑战性的。我们研究了机器学习算法在检测微血管疾病时的性能,当对分割的视网膜血管图像进行统计和拓扑摘要训练时。方法计算13个独立的描述符向量(5个统计向量,8个拓扑向量)来总结视网膜血管分割图像的形态,并训练支持向量机从总结向量中预测每张图像的疾病分类。我们评估每个描述符向量的性能,使用五倍交叉验证来估计它们的准确性。我们将这些方法应用于从四个现有数据存储库中组装的四个数据集;三个数据集包含来自其中一个存储库的分割视网膜血管图像,而第四个“全部”数据集结合了来自四个存储库的图像。结果在13个描述子向量中,统计盒计数描述子向量和拓扑泛洪描述子向量的准确率最高。在组合的“All”数据集上,Box-counting向量优于所有其他描述符,包括拓扑泛洪向量,它对不同数据集之间注释风格的差异很敏感。我们的工作代表了建立最适合识别微血管疾病和评估其当前局限性的计算方法的第一步。这些方法可以纳入自动化疾病评估工具。
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引用次数: 2
Serine proteases mediate leukocyte recruitment and hepatic microvascular injury in the acute phase following extended hepatectomy 丝氨酸蛋白酶介导扩大肝切除术后急性期的白细胞募集和肝微血管损伤
IF 2.4 4区 医学 Q2 Medicine Pub Date : 2022-12-28 DOI: 10.1111/micc.12796
Yunjie Zhang, Patrick Huber, Marc Praetner, Alice Zöllner, Lesca Holdt, Andrej Khandoga, Maximilian Lerchenberger

Objective

Post-hepatectomy liver failure (PHLF) is the main limitation of extended liver resection. The molecular mechanism and the role of leukocytes in the development of PHLF remain to be unveiled. We aimed to address the impact of serine proteases (SPs) on the acute phase after liver resection by intravitally analyzing leukocyte recruitment and changes in hemodynamics and microcirculation of the liver.

Methods

C57BL/6 mice undergoing 60% partial hepatectomy were treated with aprotinin (broad-spectrum SP inhibitor), tranexamic acid (plasmin inhibitor), or vehicle. Sham-operated animals served as controls. In vivo fluorescence microscopy was used to quantify leukocyte-endothelial interactions immediately after, as well as 120 min after partial hepatectomy in postsinusoidal venules, along with measurement of sinusoidal perfusion rate and postsinusoidal shear rate. Recruitment of leukocytes, neutrophils, T cells, and parameters of liver injury were assessed in tissue/blood samples.

Results

Leukocyte recruitment, sinusoidal perfusion failure rate, and shear rate were significantly increased in mice after 60% partial hepatectomy compared to sham-operated animals. The inhibition of SPs or plasmin significantly attenuated leukocyte recruitment and improved the perfusion rate in the remnant liver. ICAM-1 expression and neutrophil recruitment significantly increased after 60% partial hepatectomy and were strongly reduced by plasmin inhibition.

Conclusions

Endothelial activation and leukocyte recruitment in the liver in response to the increment of sinusoidal shear rate were hallmarks in the acute phase after liver resection. SPs mediated leukocyte recruitment and contributed to the impairment of sinusoidal perfusion in an ICAM-1-dependent manner in the acute phase after liver resection.

目的肝切除术后肝功能衰竭(PHLF)是扩大肝切除术的主要局限性。白细胞在PHLF发展中的分子机制和作用仍有待揭示。我们的目的是通过活体内分析白细胞的募集以及肝脏血流动力学和微循环的变化来解决丝氨酸蛋白酶(SP)对肝切除后急性期的影响。方法用抑肽酶(广谱SP抑制剂)、氨甲环酸(纤溶酶抑制剂)或赋形剂对接受60%肝部分切除术的C57BL/6小鼠进行治疗。假手术动物作为对照。体内荧光显微镜用于量化白细胞与内皮细胞的相互作用,以及120 肝部分切除后窦后小静脉min,同时测量窦灌注率和窦后剪切率。在组织/血液样本中评估白细胞、中性粒细胞、T细胞的募集和肝损伤参数。结果与假手术动物相比,60%肝部分切除后小鼠的白细胞募集、正弦灌注失败率和剪切率显著增加。SP或纤溶酶的抑制显著减弱了残余肝脏中白细胞的募集并提高了灌注率。60%肝部分切除术后ICAM-1表达和中性粒细胞募集显著增加,纤溶酶抑制显著降低。结论肝切除术后急性期内皮细胞活化和白细胞募集是肝窦剪切率增加的标志。SP介导白细胞募集,并在肝切除后的急性期以ICAM-1依赖的方式导致正弦灌注受损。
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引用次数: 0
KIR channel regulation of electrical conduction along cerebrovascular endothelium: Enhanced modulation during Alzheimer's disease KIR通道对脑血管内皮传导的调节:阿尔茨海默病期间增强的调节
IF 2.4 4区 医学 Q2 Medicine Pub Date : 2022-12-28 DOI: 10.1111/micc.12797
Md A. Hakim, Erik J. Behringer

Objective

Endothelial cell (EC) coupling occurs through gap junctions and underlies cerebral blood flow regulation governed by inward-rectifying K+ (KIR) channels. This study addressed effects of KIR channel activity on EC coupling before and during Alzheimer's disease (AD).

Methods

Intact EC tubes (width: ~90–100 μm; length: ~0.5 mm) were freshly isolated from posterior cerebral arteries of young Pre-AD (1–3 months) and aged AD (13–18 months) male and female 3xTg-AD mice. Dual intracellular microelectrodes applied simultaneous current injections (±0.5–3 nA) and membrane potential (Vm) recordings in ECs at distance ~400 μm. Elevated extracellular potassium ([K+]E; 8–15 mmol/L; reference, 5 mmol/L) activated KIR channels.

Results

Conducted Vm (∆Vm) responses ranged from ~−30 to 30 mV in response to −3 to +3 nA (linear regression, R2 ≥ .99) while lacking rectification for charge polarity or axial direction of spread. Conduction slope decreased ~10%–20% during 15 mmol/L [K+]E in Pre-AD males and AD females. 15 mmol/L [K+]E decreased conduction by ~10%–20% at lower ∆Vm thresholds in AD animals (~±20 mV) versus Pre-AD (~±25 mV). AD increased conducted hyperpolarization by ~10%–15% during 8–12 mmol/L [K+]E.

Conclusions

Brain endothelial KIR channel activity modulates bidirectional spread of vasoreactive signals with enhanced regulation of EC coupling during AD pathology.

目的内皮细胞(EC)偶联是通过间隙连接发生的,是由内向整流K+(KIR)通道调控脑血流的基础。这项研究探讨了在阿尔茨海默病(AD)之前和期间KIR通道活性对EC偶联的影响。方法完整的EC管(宽度:~90-100 μm;长度:~0.5 mm)从年轻AD前期(1-3 月)和老年AD(13-18月)雄性和雌性3xTg AD小鼠。双细胞内微电极在距离约400的EC中同时进行电流注入(±0.5–3 nA)和膜电位(Vm)记录 μm。细胞外钾升高([K+]E;8-15 mmol/L;参考,5 mmol/L)激活KIR通道。结果传导Vm(∆Vm)响应范围从~−30到30 响应−3至+3 nA的mV(线性回归,R2 ≥ .99),同时缺乏对电荷极性或轴向扩展方向的整流。传导斜率在15 AD前期男性和AD女性中的mmol/L[K+]E。15 mmol/L[K+]E使AD动物在较低∆Vm阈值下(~±20 mV)与AD前(~±25 mV)。AD在8-12期间将传导超极化增加了约10%-15% mmol/L[K+]E。结论在AD病理过程中,脑内皮KIR通道活性通过增强EC偶联调节血管反应信号的双向传播。
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引用次数: 1
Comparison of laser speckle contrast imaging with laser Doppler perfusion imaging for tissue perfusion measurement 激光散斑造影与激光多普勒灌注成像在组织灌注测量中的比较
IF 2.4 4区 医学 Q2 Medicine Pub Date : 2022-12-15 DOI: 10.1111/micc.12795
Goksel Guven, Annemieke Dijkstra, Tjallingius Martijn Kuijper, Nicole Trommel, Margriet Elisabeth van Baar, Arzu Topeli, Can Ince, Cornelis Hendrik van der Vlies

Objective

Laser-based tissue perfusion monitoring techniques have been increasingly used in animal and human research to assess blood flow. However, these techniques use arbitrary units, and knowledge about their comparability is scarce. This study aimed to model the relationship between laser speckle contrast imaging (LSCI) and laser Doppler perfusion imaging (LDPI), for measuring tissue perfusion over a wide range of blood flux values.

Methods

Fifteen healthy volunteers (53% female, median age 29 [IQR 22–40] years) were enrolled in this study. We performed iontophoresis with sodium nitroprusside on the forearm to induce regional vasodilation to increase skin blood flux. Besides, a stepwise vascular occlusion was applied on the contralateral upper arm to reduce blood flux. Both techniques were compared using a linear mixed model analysis.

Results

Baseline blood flux values measured by LSCI were 33 ± 6.5 arbitrary unit (AU) (Coefficient of variation [CV] = 20%) and by LDPI 60 ± 11.5 AU (CV = 19%). At the end of the iontophoresis protocol, the regional blood flux increased to 724 ± 412% and 259 ± 87% of baseline measured by LDPI and LSCI, respectively. On the other hand, during the stepwise vascular occlusion test, the blood flux reduced to 212 ± 40% and 412 ± 177% of its baseline at LDPI and LSCI, respectively. A strong correlation was found between the LSCI and LDPI instruments at increased blood flux with respect to baseline skin blood flux; however, the correlation was weak at reduced blood flux with respect to baseline.

Discussion

LSCI and LDPI instruments are highly linear for blood flux higher than baseline skin blood flux; however, the correlation decreased for blood flux lower than baseline. This study's findings could be a basis for using LSCI in specific patient populations, such as burn care.

目的激光组织灌注监测技术已越来越多地应用于动物和人体研究中,以评估血流。然而,这些技术使用的是任意单位,关于它们的可比性的知识很少。本研究旨在模拟激光散斑对比成像(LSCI)和激光多普勒灌注成像(LDPI)之间的关系,用于测量大范围血流量值下的组织灌注。方法选取15名健康志愿者,其中女性53%,中位年龄29岁[IQR 22-40]。我们用硝普钠离子导入前臂,诱导局部血管舒张,增加皮肤血流量。此外,在对侧上臂进行逐步血管闭塞以减少血流量。采用线性混合模型分析对两种技术进行比较。结果LSCI测定的基线血通量值为33±6.5任意单位(AU)(变异系数[CV] = 20%), LDPI测定的基线血通量值为60±11.5 AU (CV = 19%)。在离子透入方案结束时,局部血通量分别增加到LDPI和LSCI测量的基线的724±412%和259±87%。另一方面,在逐步血管闭塞试验中,LDPI和LSCI时的血通量分别下降到基线的212±40%和412±177%。与基线皮肤血流量相比,LSCI和LDPI仪器在血流量增加方面存在很强的相关性;然而,相对于基线,在血流量降低时相关性较弱。LSCI和LDPI仪器的血流量高于基线皮肤血流量呈高度线性;然而,当血流量低于基线时,相关性降低。这项研究的发现可能是在特定患者群体中使用LSCI的基础,例如烧伤护理。
{"title":"Comparison of laser speckle contrast imaging with laser Doppler perfusion imaging for tissue perfusion measurement","authors":"Goksel Guven,&nbsp;Annemieke Dijkstra,&nbsp;Tjallingius Martijn Kuijper,&nbsp;Nicole Trommel,&nbsp;Margriet Elisabeth van Baar,&nbsp;Arzu Topeli,&nbsp;Can Ince,&nbsp;Cornelis Hendrik van der Vlies","doi":"10.1111/micc.12795","DOIUrl":"10.1111/micc.12795","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Laser-based tissue perfusion monitoring techniques have been increasingly used in animal and human research to assess blood flow. However, these techniques use arbitrary units, and knowledge about their comparability is scarce. This study aimed to model the relationship between laser speckle contrast imaging (LSCI) and laser Doppler perfusion imaging (LDPI), for measuring tissue perfusion over a wide range of blood flux values.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Fifteen healthy volunteers (53% female, median age 29 [IQR 22–40] years) were enrolled in this study. We performed iontophoresis with sodium nitroprusside on the forearm to induce regional vasodilation to increase skin blood flux. Besides, a stepwise vascular occlusion was applied on the contralateral upper arm to reduce blood flux. Both techniques were compared using a linear mixed model analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Baseline blood flux values measured by LSCI were 33 ± 6.5 arbitrary unit (AU) (Coefficient of variation [CV] = 20%) and by LDPI 60 ± 11.5 AU (CV = 19%). At the end of the iontophoresis protocol, the regional blood flux increased to 724 ± 412% and 259 ± 87% of baseline measured by LDPI and LSCI, respectively. On the other hand, during the stepwise vascular occlusion test, the blood flux reduced to 212 ± 40% and 412 ± 177% of its baseline at LDPI and LSCI, respectively. A strong correlation was found between the LSCI and LDPI instruments at increased blood flux with respect to baseline skin blood flux; however, the correlation was weak at reduced blood flux with respect to baseline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>LSCI and LDPI instruments are highly linear for blood flux higher than baseline skin blood flux; however, the correlation decreased for blood flux lower than baseline. This study's findings could be a basis for using LSCI in specific patient populations, such as burn care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7f/de/MICC-30-0.PMC10078364.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9267280","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: 3
Impairment of endothelial progenitor cells in women after kidney transplantation 肾移植后女性内皮祖细胞损伤的研究
IF 2.4 4区 医学 Q2 Medicine Pub Date : 2022-12-09 DOI: 10.1111/micc.12794
Nadia Meyer, Katja Richter, Lars Brodowski, Constantin von Kaisenberg, Anette Melk, Bernhard Schmidt, Florian P. Limbourg, Bianca Schröder-Heurich, Frauke von Versen-Höynck

Objective

The long-term survival of kidney transplant patients has substantially improved. However, there is a higher risk for cardiovascular events after transplantation, partly due to immunosuppression. A diminished number of endothelial progenitor cells (EPCs), which play an important role in angiogenesis and the repair of endothelial damage, are associated with an increased cardiovascular risk. The aim of this study was to evaluate whether kidney transplantation affects EPCs in women.

Methods

Twenty-four healthy women and 22 female kidney transplant recipients were recruited. The ratio of angiogenic and non-angiogenic circulating progenitor cells (CPCs) was determined by multicolor flow cytometry and related to clinical parameters. Cord blood-derived endothelial colony-forming cells (ECFCs), a proliferative subgroup of endothelial progenitor cells, were treated with pooled sera from transplant patients or healthy controls and tested for their functional integrity using in vitro models.

Results

Kidney transplant recipients displayed a reduced ratio of angiogenic and non-angiogenic CPCs compared to healthy controls. Differences were especially pronounced in premenopausal women. Exposure to sera of transplanted women led to a significant impairment of ECFC proliferation, migration, and angiogenesis ability.

Conclusions

Alterations of EPC populations may contribute to the higher cardiovascular risks after organ transplantation and should be considered in therapeutic strategies.

目的肾移植患者的长期生存率有了显著提高。然而,移植后发生心血管事件的风险更高,部分原因是免疫抑制。在血管生成和内皮损伤修复中发挥重要作用的内皮祖细胞(EPC)数量减少与心血管风险增加有关。本研究的目的是评估肾移植是否影响女性的EPCs。方法选择24名健康女性和22名女性肾移植受者。通过多色流式细胞术测定血管生成和非血管生成循环祖细胞(CPCs)的比例,并与临床参数相关。脐血来源的内皮集落形成细胞(ECFC)是内皮祖细胞的增殖亚群,用来自移植患者或健康对照的合并血清处理,并使用体外模型测试其功能完整性。结果与健康对照组相比,肾移植受者显示出血管生成和非血管生成CPCs的比例降低。差异在绝经前妇女中尤为明显。暴露于移植妇女的血清导致ECFC增殖、迁移和血管生成能力显著受损。结论EPC人群的改变可能导致器官移植后心血管风险的增加,应在治疗策略中加以考虑。
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引用次数: 0
Engineered models of the lymphatic vascular system: Past, present, and future 淋巴血管系统的工程模型:过去、现在和未来
IF 2.4 4区 医学 Q2 Medicine Pub Date : 2022-11-22 DOI: 10.1111/micc.12793
Amirali Selahi, Abhishek Jain

The lymphatic vascular system is crucial for optimizing body fluid level, regulating immune function, and transporting lipid. Relative to the experimental models to investigate blood vasculature, there are significantly fewer tools to explore lymphatics. Although in vivo studies have contributed to major discoveries in the field, finding and characterizing lymphatic specific markers has opened the door to isolating lymphatic vessels and cells for building ex vivo and in vitro platforms. These preparations have enabled the study and analysis of lymphatic vasculature in various physiological and pathophysiological conditions leading to a better understanding of cellular expressions and signaling. In this review, a broad range of ex vivo and in vitro engineered models are highlighted and categorized based on the major lymphatic function they model including contractile function, inflammation, drainage and immune regulation, lymphangiogenesis, and tumor-lymphatic interactions. Then, the novel 3D engineered tissues are introduced consisting of acellularized scaffolds and hydrogels to form vessels and cellular structures close to in vivo morphology. This paper also compares traditional in vitro methods with recent technologies and elaborates on the inherent advantages and limitations of each preparation by critically discussing simplest to most complex tissue-cellular structures. It concludes with an outlook of the lymphatic vasculature models and the possible future direction of contemporary tools, such as organ-on-chips.

淋巴血管系统对优化体液水平、调节免疫功能和运输脂质至关重要。相对于研究血管系统的实验模型,研究淋巴管的工具明显较少。尽管体内研究为该领域的重大发现做出了贡献,但淋巴特异性标记物的发现和表征为分离淋巴管和细胞以建立离体和体外平台打开了大门。这些制剂使淋巴血管在各种生理和病理生理条件下的研究和分析成为可能,从而更好地理解细胞表达和信号传导。在这篇综述中,广泛的体外和体外工程模型被强调和分类基于主要淋巴功能,包括收缩功能,炎症,引流和免疫调节,淋巴管生成和肿瘤-淋巴相互作用。然后,介绍了由脱细胞支架和水凝胶组成的新型三维工程组织,以形成接近体内形态的血管和细胞结构。本文还比较了传统的体外方法与最近的技术,并通过批判性地讨论最简单到最复杂的组织细胞结构,详细阐述了每种制备方法的固有优点和局限性。最后展望了淋巴血管模型和当代工具(如器官芯片)可能的未来方向。
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引用次数: 4
Abstracts from the 47th Annual Meeting of Japanese Society for Microcirculation 日本微循环学会第47届年会上论文摘要
IF 2.4 4区 医学 Q2 Medicine Pub Date : 2022-11-19 DOI: 10.1111/micc.12784
We aneurysms based the in vascular endothelial cells triggers aneurysm development. Methods : We investigated the role of P2X4 purinoceptor, which is involved in flow- sensitive mechanisms in vascular endothelial cells, in the development of cerebral aneurysms by using the aneurysm-induced animal model. We also prospectively enrolled human patients with unruptured cerebral aneurysms, observed them for 3 years with cerebrovascular 3D imaging and carotid artery echo -cardiography, and compared the hemodynamic environments of the growth group with those of the non- growth group using computa-tional fluid dynamics (CFD) technique. Results : The incidence of cerebral aneurysms in aneurysm- induced P2X4 (−/−) mice was significantly lower than that in P2X4 (+/+) mice, and the incidence of cerebral aneurysms in aneurysm- induced rats treated with a P2X4 inhibitor, paroxetine was significantly lower than that in the non- treated group. Paroxetine treatment also significantly suppressed aneurysm growth. In the clinical study of human unruptured cerebral aneurysms, 461 patients were enrolled, and during the 3- year observation period, 38 aneurysms enlarged and 209 ones did not. In the CFD analysis, the magnitude of wall shear stress and transWSS, a metrics for shear stress disturbance, was significantly increased in the enlarged group, especially in the aneurysm neck. Normal brain function depends on stable cerebral blood flow and cerebral autoregulation. Cerebral blood flow is maintained even when blood pressure fluctuates. However, microcirculation in the cortex is not well understood when blood pressure drops rapidly. The purpose of this study was to determine oxyhemoglobin (O 2 Hb) changes, the indicator of cortical blood flow changes, during hypotension induced by thigh cuff release. Ten healthy students participated in this study. They were seated in a recumbent position in a quiet room. The cuffs of digital tourniquets were placed on both thighs and inflated to 250 mmHg for 5 min after 5 min rest, followed by deflation for 5 min. Right (R- ) and left (L- ) prefrontal cortex (PFC) O 2 Hb levels were measured using a multi- channel near- infrared spectroscopy system (LABNIRS; Shimadzu Co). O 2 Hb levels for each area were measured. Beat- to- beat mean arterial pressure (MAP) was recorded by volume clamping the finger pulse with a finger photoplethysmograph (Finometer; Finapres Medical Systems) on the left middle finger. O 2 Hb and MAP were averaged 1- sec epoch throughout the experi-ment. This study was approved by the Ethics Committee of Niigata University of Health and Welfare (18649- 210618). The decrease in MAP after the cuff release was 31.3 ± 5.6 mmHg. The decrease in O 2 Hb levels in the L- PFC (0.196 ± 0.088 mM∙cm) was larger than that in R- PFC (0.165 ± 0.072 mM∙cm) ( p < .05). These results suggest that the effect of hypotension induced by thigh cuff release on cortical blood flow might be different between cortical regions. Background : Pers
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引用次数: 0
Lentiviral overexpression of VEGFC in transplanted MSCs leads to resolution of swelling in a mouse tail lymphedema model 慢病毒在移植骨髓间充质干细胞中过表达VEGFC导致小鼠尾部淋巴水肿模型肿胀消退
IF 2.4 4区 医学 Q2 Medicine Pub Date : 2022-11-12 DOI: 10.1111/micc.12792
Eleftheria Michalaki, Josephine M. Rudd, Lauren Liebman, Rahul Wadhwani, Levi B. Wood, Nick J. Willett, J. Brandon Dixon

Background

Dysfunction of the lymphatic system following injury, disease, or cancer treatment can lead to lymphedema, a debilitating condition with no cure. Despite the various physical therapy and surgical options available, most treatments are palliative and fail to address the underlying lymphatic vascular insufficiency driving lymphedema progression. Stem cell therapy provides a promising alternative in the treatment of various chronic diseases with a wide range of therapeutic effects that reduce inflammation, fibrosis, and oxidative stress, while promoting lymphatic vessel (LV) regeneration. Specifically, stem cell transplantation is suggested to promote LV restoration, rebuild lymphatic circulation, and thus potentially be utilized towards an effective lymphedema treatment. In addition to stem cells, studies have proposed the administration of vascular endothelial growth factor C (VEGFC) to promote lymphangiogenesis and decrease swelling in lymphedema.

Aims

Here, we seek to combine the benefits of stem cell therapy, which provides a cellular therapeutic approach that can respond to the tissue environment, and VEGFC administration to restore lymphatic drainage.

Materials & Methods

Specifically, we engineered mesenchymal stem cells (MSCs) to overexpress VEGFC using a lentiviral vector (hVEGFC MSC) and investigated their therapeutic efficacy in improving LV function and tissue swelling using near infrared (NIR) imaging, and lymphatic regeneration in a single LV ligation mouse tail lymphedema model.

Results

First, we showed that overexpression of VEGFC using lentiviral transduction led to an increase in VEGFC protein synthesis in vitro. Then, we demonstrated hVEGFC MSC administration post-injury significantly increased the lymphatic contraction frequency 14-, 21-, and 28-days post-surgery compared to the control animals (MSC administration) in vivo, while also reducing tail swelling 28-days post-surgery compared to controls.

Conclusion

Our results suggest a therapeutic potential of hVEGFC MSC in alleviating the lymphatic dysfunction observed during lymphedema progression after secondary injury and could provide a promising approach to enhancing autologous cell therapy for treating lymphedema.

背景淋巴系统在受伤、疾病或癌症治疗后的功能障碍可导致淋巴水肿,这是一种无法治愈的衰弱性疾病。尽管有各种物理治疗和手术选择,但大多数治疗都是姑息性的,无法解决导致淋巴水肿进展的潜在淋巴管功能不全。干细胞疗法为治疗各种慢性疾病提供了一种有前景的替代方案,具有广泛的治疗效果,可以减少炎症、纤维化和氧化应激,同时促进淋巴管(LV)再生。具体而言,干细胞移植可促进左心室恢复,重建淋巴循环,从而有可能用于有效的淋巴水肿治疗。除了干细胞外,研究还提出了血管内皮生长因子C(VEGFC)的给药,以促进淋巴管生成并减少淋巴水肿中的肿胀。目的在这里,我们寻求将干细胞治疗和VEGFC给药的好处结合起来,干细胞治疗提供了一种可以对组织环境做出反应的细胞治疗方法,以恢复淋巴引流。材料&;方法具体而言,我们使用慢病毒载体(hVEGFC-MSC)改造间充质干细胞(MSC)以过表达VEGFC,并使用近红外(NIR)成像研究其在改善左心室功能和组织肿胀方面的治疗效果,以及在单LV结扎小鼠尾部淋巴水肿模型中的淋巴再生。结果首先,我们发现使用慢病毒转导的VEGFC过表达导致体外VEGFC蛋白合成增加。然后,我们证明,与体内对照动物(MSC给药)相比,损伤后给予hVEGFC MSC显著增加了手术后14、21和28天的淋巴收缩频率,同时与对照相比,也减少了手术后28天的尾部肿胀。结论hVEGFC-MSC在减轻继发性损伤后淋巴水肿进展过程中观察到的淋巴功能障碍方面具有治疗潜力,可为加强自体细胞治疗淋巴水肿提供一种有前景的方法。
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引用次数: 1
GATA2 regulates blood/lymph separation in a platelet-dependent and lymphovenous valve-independent manner GATA2以血小板依赖和淋巴静脉瓣膜不依赖的方式调节血液/淋巴分离
IF 2.4 4区 医学 Q2 Medicine Pub Date : 2022-10-05 DOI: 10.1111/micc.12787
Md. Riaj Mahamud, Xin Geng, Lijuan Chen, Zoheb Ahmed, Yenchun Ho, R. Sathish Srinivasan

Introduction

Lymphatic vessels collect interstitial fluid, immune cells, and digested lipids and return these bodily fluids to blood through two pairs of lymphovenous valves (LVVs). Like other cardiovascular valves LVVs prevent the backflow of blood into the lymphatic vessels. In addition to LVVs, platelets are necessary to prevent the entry of blood into the lymphatic vessels. Platelet thrombi are observed at LVVs suggesting that LVVs and platelets function in synergy to regulate blood/lymphatic separation.

Objectives

The primary objective of this work is to determine whether platelets can regulate blood/lymph separation independently of LVVs.

Methods

The transcription factor GATA2 is necessary for the development of both LVVs and hematopoietic stem cells. Using various endothelial- and hematopoietic cell expressed Cre-lines, we conditionally deleted Gata2. We hypothesized that this strategy would identify the tissue- and time-specific roles of GATA2 and reveal whether platelets and LVVs can independently regulate blood/lymph separation.

Results

Lymphatic vasculature-specific deletion of Gata2 results in the absence of LVVs without compromising blood/lymph separation. In contrast, deletion of GATA2 from both lymphatic vasculature and hematopoietic cells results in the absence of LVVs, reduced number of platelets and blood-filled lymphatic vasculature.

Conclusion

GATA2 promotes blood/lymph separation through platelets. Furthermore, LVVs are the only known sites of interaction between blood and lymphatic vessels. The fact that blood is able to enter the lymphatic vessels of mice lacking LVVs and platelets indicates that under these circumstances the lymphatic and blood vessels are connected at yet to be identified sites.

淋巴管收集间质液、免疫细胞和消化的脂质,并通过两对淋巴静脉瓣膜(LVVs)将这些体液送回血液。像其他心血管瓣膜一样,左心室防止血液回流到淋巴管。除了左心室外,血小板也是防止血液进入淋巴管所必需的。在左心室观察到血小板血栓,提示左心室和血小板协同作用调节血液/淋巴分离。这项工作的主要目的是确定血小板是否可以独立于lvv调节血液/淋巴分离。方法转录因子GATA2是LVVs和造血干细胞发育所必需的。使用多种内皮细胞和造血细胞表达的cre细胞系,我们有条件地删除了Gata2。我们假设这种策略可以确定GATA2的组织和时间特异性作用,并揭示血小板和lvv是否可以独立调节血液/淋巴分离。结果淋巴血管特异性缺失Gata2导致lvv缺失,但不影响血淋巴分离。相比之下,淋巴血管和造血细胞中GATA2的缺失导致lvv缺失,血小板数量减少,淋巴血管充血。结论GATA2通过血小板促进血淋巴分离。此外,左心室是唯一已知的血液和淋巴管相互作用的部位。血液能够进入缺乏lvv和血小板的小鼠的淋巴管这一事实表明,在这种情况下,淋巴管和血管在尚未确定的位置连接。
{"title":"GATA2 regulates blood/lymph separation in a platelet-dependent and lymphovenous valve-independent manner","authors":"Md. Riaj Mahamud,&nbsp;Xin Geng,&nbsp;Lijuan Chen,&nbsp;Zoheb Ahmed,&nbsp;Yenchun Ho,&nbsp;R. Sathish Srinivasan","doi":"10.1111/micc.12787","DOIUrl":"10.1111/micc.12787","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Lymphatic vessels collect interstitial fluid, immune cells, and digested lipids and return these bodily fluids to blood through two pairs of lymphovenous valves (LVVs). Like other cardiovascular valves LVVs prevent the backflow of blood into the lymphatic vessels. In addition to LVVs, platelets are necessary to prevent the entry of blood into the lymphatic vessels. Platelet thrombi are observed at LVVs suggesting that LVVs and platelets function in synergy to regulate blood/lymphatic separation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The primary objective of this work is to determine whether platelets can regulate blood/lymph separation independently of LVVs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The transcription factor GATA2 is necessary for the development of both LVVs and hematopoietic stem cells. Using various endothelial- and hematopoietic cell expressed Cre-lines, we conditionally deleted Gata2. We hypothesized that this strategy would identify the tissue- and time-specific roles of GATA2 and reveal whether platelets and LVVs can independently regulate blood/lymph separation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Lymphatic vasculature-specific deletion of Gata2 results in the absence of LVVs without compromising blood/lymph separation. In contrast, deletion of GATA2 from both lymphatic vasculature and hematopoietic cells results in the absence of LVVs, reduced number of platelets and blood-filled lymphatic vasculature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>GATA2 promotes blood/lymph separation through platelets. Furthermore, LVVs are the only known sites of interaction between blood and lymphatic vessels. The fact that blood is able to enter the lymphatic vessels of mice lacking LVVs and platelets indicates that under these circumstances the lymphatic and blood vessels are connected at yet to be identified sites.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12787","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9489317","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: 1
期刊
Microcirculation
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