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RNA-seq profiling reveals different pathways between remodeled vessels and myocardium in hypertrophic cardiomyopathy RNA-seq分析揭示了肥厚性心肌病重构血管和心肌之间的不同途径
IF 2.4 4区 医学 Q2 Medicine Pub Date : 2022-10-05 DOI: 10.1111/micc.12790
Annalinda Pisano, Loredana Le Pera, Raffaella Carletti, Bruna Cerbelli, Maria G. Pignataro, Angelina Pernazza, Fabrizio Ferre, Maria Lombardi, Davide Lazzeroni, Iacopo Olivotto, Ornella E. Rimoldi, Chiara Foglieni, Paolo G. Camici, Giulia d'Amati

Objective

Coronary microvascular dysfunction (CMD) is a key pathophysiological feature of hypertrophic cardiomyopathy (HCM), contributing to myocardial ischemia and representing a critical determinant of patients' adverse outcome. The molecular mechanisms underlying the morphological and functional changes of CMD are still unknown. Aim of this study was to obtain insights on the molecular pathways associated with microvessel remodeling in HCM.

Methods

Interventricular septum myectomies from patients with obstructive HCM (n = 20) and donors' hearts (CTRL, discarded for technical reasons, n = 7) were collected. Remodeled intramyocardial arterioles and cardiomyocytes were microdissected by laser capture and next-generation sequencing was used to delineate the transcriptome profile.

Results

We identified 720 exclusive differentially expressed genes (DEGs) in cardiomyocytes and 1315 exclusive DEGs in remodeled arterioles of HCM. Performing gene ontology and pathway enrichment analyses, we identified selectively altered pathways between remodeled arterioles and cardiomyocytes in HCM patients and controls.

Conclusions

We demonstrate the existence of distinctive pathways between remodeled arterioles and cardiomyocytes in HCM patients and controls at the transcriptome level.

目的冠状动脉微血管功能障碍(CMD)是肥厚性心肌病(HCM)的关键病理生理特征,有助于心肌缺血,是患者不良结局的关键决定因素。其形态和功能变化的分子机制尚不清楚。本研究的目的是了解HCM微血管重构的相关分子途径。方法收集梗阻性HCM患者(n = 20)的室间隔肌瘤切除术和供体心脏(CTRL,因技术原因丢弃,n = 7)。重构的心内小动脉和心肌细胞通过激光捕获进行显微解剖,并使用下一代测序来描绘转录组谱。结果在心肌细胞中鉴定出720个特异性差异表达基因(deg),在HCM重构小动脉中鉴定出1315个特异性差异表达基因(deg)。通过基因本体论和途径富集分析,我们在HCM患者和对照组中发现了重构小动脉和心肌细胞之间选择性改变的途径。在转录组水平上,我们证明了HCM患者和对照组中重构小动脉和心肌细胞之间存在不同的通路。
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引用次数: 1
Impact of Goreisan components on rat mesenteric collecting lymphatic vessel pumping 葛瑞山成分对大鼠肠系膜集淋巴管泵送的影响
IF 2.4 4区 医学 Q2 Medicine Pub Date : 2022-09-28 DOI: 10.1111/micc.12788
Michiko Jo, Andrea N. Trujillo, Naotoshi Shibahara, Jerome W. Breslin

Background

Goreisan is a traditional herbal formulation with diuretic properties tested as a clinical therapeutic to alleviate lymphedema in Japan. The present study aimed to determine how Goreisan and its five different components affect lymphatic pump function.

Methods

Mesenteric collecting lymphatics were isolated from anesthetized Sprague–Dawley rats and mounted on resistance-matched glass micropipettes in a 37°C physiological salt solution bath for studies. Diameter was continuously measured to obtain the following lymphatic pump parameters: contraction frequency (CF), end diastolic diameter (EDD), and end systolic diameter (ESD), contraction amplitude (AMP), ejection fraction (EF), and fractional pump flow (FPF). Goreisan and each of its components (Cinnamomi Cortex, Atractylodis Rhizoma, Alismatis Rhizoma, Polyporus, and Poria) were applied to the bath at concentrations of 1–30 μg/mL.

Results

The results show that while Goreisan causes no significant changes to lymphatic pumping, Alismatis Rhizoma and Polyporus each significantly reduce CF and FPF. In addition, rats that received oral administration of Goreisan and Alismatis Rhizoma for 1 week had elevated expression of VEGFR-3 in their mesenteric collecting lymphatics.

Conclusions

Collectively, the results suggest that some components of Goreisan have a direct, rapid impact on lymphatic pumping. These findings provide new insights but also raise new questions about the therapeutic potential of Goreisan in patients with secondary lymphedema.

背景Goreisan是一种传统的草药配方,具有利尿的特性,在日本作为一种临床治疗方法来缓解淋巴水肿。本研究旨在确定Goreisan及其五种不同成分如何影响淋巴泵功能。方法分离麻醉后的sd大鼠肠系膜收集淋巴管,置于37℃生理盐液浴中进行实验研究。连续测量管径,获得以下淋巴泵参数:收缩频率(CF)、舒张末内径(EDD)、收缩末内径(ESD)、收缩幅值(AMP)、射血分数(EF)和泵流量分数(FPF)。Goreisan和它的每个组件(肉桂的皮层,Atractylodis根茎,Alismatis根茎,Polyporus,和云苓)被应用于浴浓度的外墙面μg / mL。结果丹参对大鼠淋巴泵无明显影响,泽泻和茯苓均能显著降低CF和FPF。此外,口服黄芩和泽泻1周的大鼠肠系膜集淋巴中VEGFR-3的表达升高。综上所述,结果表明高丽散的某些成分对淋巴泵送有直接、快速的影响。这些发现提供了新的见解,但也提出了关于Goreisan在继发性淋巴水肿患者中的治疗潜力的新问题。
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引用次数: 3
Irisin inhibits NLRP3 inflammasome activation in HG/HF incubated cardiac microvascular endothelial cells with H/R injury 鸢尾素抑制HG/HF培养H/R损伤心肌微血管内皮细胞NLRP3炎性体活化
IF 2.4 4区 医学 Q2 Medicine Pub Date : 2022-09-24 DOI: 10.1111/micc.12786
Chao Xin, Jinglong Zhang, Ningbo Hao, Jianan Wang, Hui Liu, Hanwen Wei, Yong Wang, Chengzhu Wang, Shuo Wang, Chengrong Zheng, Zheng Zhang, Zhitao Jin

Purpose

NLRP3 inflammasome mediates myocardial ischemia/reperfusion (MI/R) injury and diabetic vascular endothelia dysfunction. However, the role of NLRP3 inflammasome in MI/R injury with diabetes has not been fully described. Irisin plays an important role in anti-inflammation and improves endothelial function in type 2 diabetes. The current study aimed to investigate the effect of irisin on regulating NLRP3 inflammasome activation in diabetic vascular endothelia dysfunction.

Methods

Cardiac microvascular endothelial cells (CMECs) were cultured and subjected to high glucose/high fat (HG/HF) receiving hypoxia/reoxygenation (H/R) with irisin incubation or not. Then, apoptosis, viability, migration, NO secretion, and inflammasome activation were examined.

Results

The hypoxic CMECs exhibited increased apoptosis, impaired viability, and migration, even decreased NO secretion and enhanced inflammasome activation. Moreover, irisin incubation decreased NLRP3 activation and attenuated cell injury in HG/HF cultured CMECs subjected to H/R injury, which was abolished by NLRP3 inflammasome activation. Meanwhile, NLRP3 inflammasome siRNA also attenuated H/R injury in CMECs under HG/HF condition.

Conclusion

The current study demonstrated for the first time that irisin inhibits NLRP3 inflammasome activation in CMECs as a novel mechanism in myocardial ischemia/reperfusion injury in diabetes.

目的NLRP3炎性体介导心肌缺血再灌注(MI/R)损伤和糖尿病血管内皮功能障碍。然而,NLRP3炎性体在糖尿病心肌梗死/再灌注损伤中的作用尚未得到充分描述。鸢尾素在2型糖尿病患者中具有抗炎和改善内皮功能的重要作用。本研究旨在探讨鸢尾素在糖尿病血管内皮功能障碍中调节NLRP3炎性体激活的作用。方法培养心脏微血管内皮细胞(CMECs),进行高糖/高脂(HG/HF)缺氧/再氧化(H/R),鸢尾素孵育或不孵育。然后检测细胞凋亡、活力、迁移、NO分泌和炎性体活化。结果缺氧cmec细胞凋亡增加,细胞活力和迁移能力受损,一氧化氮分泌减少,炎性体活化增强。此外,鸢尾素孵育可降低HG/HF培养的H/R损伤cmes的NLRP3激活并减轻细胞损伤,而NLRP3炎性体激活可消除H/R损伤。同时,NLRP3炎性小体siRNA也能减轻HG/HF条件下cmes的H/R损伤。结论本研究首次证实鸢尾素抑制CMECs NLRP3炎性体激活是糖尿病心肌缺血再灌注损伤的新机制。
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引用次数: 1
Visualizing the Microcirculation 可视化微循环
IF 2.4 4区 医学 Q2 Medicine Pub Date : 2022-09-20 DOI: 10.1111/micc.12785
Janaka Senarathna, Arvind P. Pathak
Over the last century, scientific discoveries have revealed the critical role of the microcirculation in maintaining homeostasis and the etiology of diseases ranging from cancer to COVID-19. These advances have coincided with and even been made possible by the exponential progress in imaging and visualization techniques capable of characterizing the structural and functional diversity of the microcirculation. Consequently, this special issue (SI) showcases a broad selection of tools and methods for elucidating the role of the microcirculation in health and disease. In this exciting compendium of globally contributed articles, authors investigate in vitro and in vivo models, describe new imaging methods spanning from the endothelial cell to the whole organ scale, as well as analytical approaches focused on the microvascular and lymphatic systems. Also included are articles describing the use of ultrasound and photoacoustic imaging of the microcirculation in the clinical and preclinical realms. We believe this SI on "Visualizing the Microcirculation" contains something for everyone, from basic scientists to clinicians interested in the microcirculation.
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引用次数: 0
Analysis and visualization methods for detecting functional activation using laser speckle contrast imaging 利用激光散斑对比成像检测功能激活的分析和可视化方法
IF 2.4 4区 医学 Q2 Medicine Pub Date : 2022-09-07 DOI: 10.1111/micc.12783
Peng Hu, Bochao Niu, Hang Yang, Yang Xia, Donna Chen, Chun Meng, Ke Chen, Bharat Biswal

Background

Previous studies have used regional cerebral blood flow (CBF) hemodynamic response to measure brain activities. In this work, we use a laser speckle contrast imaging (LSCI) apparatus to sample the CBF activation in somatosensory cortex (S1BF) with repetitive whisker stimulation. Traditionally, the CBF activations were processed by depicting the change percentage above baseline; however, it is not clear how different methods influence the detection of activations.

Aims

Thus, in this work we investigate the influence of different methods to detect activations in LSCI.

Materials & Methods

First, principal component analysis (PCA) was performed to denoise the CBF signal. As the signal of the first principal component (PC1) showed the highest correlation with the S1BF CBF response curve, PC1 was used in the subsequent analyses. Then, we used fast Fourier transform (FFT) to evaluate the frequency properties of the LSCI images and the activation map was generated based on the amplitude of the central frequency. Furthermore, Pearson's correlation coefficient (C–C) analysis and a general linear model (GLM) were performed to estimate the S1BF activation based on the time series of PC1.

Results

We found that GLM performed better in identifying activation than C–C. Additionally, the activation maps generated by FFT were similar to those obtained by GLM. Particularly, the superficial vein and arterial vessels separated the activation region as segmented activated areas, and the regions with unresolved vessels showed a common activation for whisker stimulation.

Discussion and Conclusion

Our research analyzed the extent to which PCA can extract meaningful information from the signal and we compared the performance for detecting brain functional activation between different methods that rely on LSCI. This can be used as a reference for LSCI researchers on choosing the best method to estimate brain activation.

以往的研究使用脑区域血流动力学反应(CBF)来测量脑活动。在这项工作中,我们使用激光散斑对比成像(LSCI)设备对重复须刺激体感觉皮层(S1BF)的CBF激活进行了采样。传统上,CBF激活是通过描述高于基线的变化百分比来处理的;然而,目前尚不清楚不同的方法如何影响激活检测。因此,在这项工作中,我们研究了不同方法检测LSCI激活的影响。材料,方法首先采用主成分分析(PCA)对脑血流信号进行去噪处理。由于第一主成分(PC1)信号与S1BF CBF响应曲线的相关性最高,因此将PC1用于后续分析。然后,利用快速傅里叶变换(FFT)对LSCI图像的频率特性进行评估,并根据中心频率的幅值生成激活图;基于PC1的时间序列,采用Pearson相关系数(C-C)分析和一般线性模型(GLM)估计S1BF的激活。结果我们发现GLM比C-C更能识别激活。此外,FFT生成的激活图与GLM获得的激活图相似。特别是,浅表静脉和动脉血管将激活区分离为分段激活区,并且未解决的血管区域显示出对须刺激的共同激活。我们的研究分析了PCA从信号中提取有意义信息的程度,并比较了依赖LSCI的不同方法在检测脑功能激活方面的性能。这可以为LSCI研究者选择最佳的脑激活估计方法提供参考。
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引用次数: 2
Histone-stimulated platelet adhesion to mouse cremaster venules in vivo is dependent on von Willebrand factor 组蛋白刺激的血小板对小鼠小静脉的粘附依赖于血管性血友病因子
IF 2.4 4区 医学 Q2 Medicine Pub Date : 2022-09-03 DOI: 10.1111/micc.12782
Justin A. Courson, Fong W. Lam, Kimberly W. Langlois, Rolando E. Rumbaut

Objective

Extracellular histones are known mediators of platelet activation, inflammation, and thrombosis. Von Willebrand Factor (vWF) and Toll-like receptor 4 (TLR4) have been implicated in pro-inflammatory and prothrombotic histone responses. The objective of this study was to assess the role of vWF and TLR4 on histone-induced platelet adhesion in vivo.

Methods

Intravital microscopy of the mouse cremaster microcirculation, in the presence of extracellular histones or saline control, was conducted in wild-type, vWF-deficient, and TLR4-deficient mice to assess histone-mediated platelet adhesion. Platelet counts following extracellular histone exposure were conducted. Platelets were isolated from vWF-deficient mice and littermates to assess the role of vWF on histone-induced platelet aggregation.

Results

Histones promoted platelet adhesion to cremaster venules in vivo in wild-type animals, as well as in TLR4-deficient mice to a comparable degree. Histones did not lead to increased platelet adhesion in vWF-deficient mice, in contrast to littermate controls. In all genotypes, histones resulted in thrombocytopenia. Histone-induced platelet aggregation ex vivo was similar in vWF-deficient mice and littermate controls.

Conclusions

Histone-induced platelet adhesion to microvessels in vivo is vWF-dependent and TLR4-independent. Platelet-derived vWF was not necessary for histone-induced platelet aggregation ex vivo. These data are consistent with the notion that endothelial vWF, rather than platelet vWF, mediates histone-induced platelet adhesion in vivo.

目的细胞外组蛋白是已知的血小板活化、炎症和血栓形成的介质。血管性血友病因子(vWF)和toll样受体4 (TLR4)参与促炎和血栓形成前组蛋白反应。本研究的目的是评估vWF和TLR4在组蛋白诱导的血小板粘附中的作用。方法对野生型、vwf缺陷型和tlr4缺陷型小鼠,在细胞外组蛋白存在或生理盐水对照下,进行小鼠乳糜微循环活体显微镜观察,以评估组蛋白介导的血小板粘附。细胞外组蛋白暴露后进行血小板计数。从vWF缺陷小鼠和窝仔中分离血小板,以评估vWF对组蛋白诱导的血小板聚集的作用。结果组蛋白在野生型动物和tlr4缺陷小鼠体内均可促进血小板粘附到小静脉。与对照组相比,组蛋白不会导致vwf缺陷小鼠血小板粘附增加。在所有基因型中,组蛋白导致血小板减少。组蛋白诱导的体外血小板聚集在vwf缺陷小鼠和同窝对照中相似。结论组蛋白诱导的血小板对微血管的粘附是vwf依赖性的,与tlr4无关。血小板来源的vWF对于组蛋白诱导的体外血小板聚集不是必需的。这些数据与内皮细胞vWF而不是血小板vWF在体内介导组蛋白诱导的血小板粘附的观点一致。
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引用次数: 0
Recent advancement of imaging strategies of the lymphatic system: Answer to the decades old questions 淋巴系统成像策略的最新进展:回答几十年的老问题
IF 2.4 4区 医学 Q2 Medicine Pub Date : 2022-08-16 DOI: 10.1111/micc.12780
Priyanka Banerjee, Sukanya Roy, Sanjukta Chakraborty

The role of the lymphatic system in maintaining tissue homeostasis and a number of different pathophysiological conditions has been well established. The complex and delicate structure of the lymphatics along with the limitations of conventional imaging techniques make lymphatic imaging particularly difficult. Thus, in-depth high-resolution imaging of lymphatic system is key to understanding the progression of lymphatic diseases and cancer metastases and would greatly benefit clinical decisions. In recent years, the advancement of imaging technologies and development of new tracers suitable for clinical applications has enabled imaging of the lymphatic system in both clinical and pre-clinical settings. In this current review, we have highlighted the advantages and disadvantages of different modern techniques such as near infra-red spectroscopy (NIRS), positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI) and fluorescence optical imaging, that has significantly impacted research in this field and has led to in-depth insights into progression of pathological states. This review also highlights the use of current imaging technologies, and tracers specific for immune cell markers to identify and track the immune cells in the lymphatic system that would help understand disease progression and remission in immune therapy regimen.

淋巴系统在维持组织稳态和许多不同病理生理条件中的作用已经得到了很好的证实。淋巴管的复杂和精细结构以及传统成像技术的局限性使得淋巴管成像特别困难。因此,深入的高分辨率淋巴系统成像是了解淋巴疾病进展和癌症转移的关键,并将极大地有利于临床决策。近年来,成像技术的进步和适合临床应用的新型示踪剂的开发,使淋巴系统的成像在临床和临床前设置。在这篇综述中,我们重点介绍了近红外光谱(NIRS)、正电子发射断层扫描(PET)、计算机断层扫描(CT)、磁共振成像(MRI)和荧光光学成像等不同现代技术的优缺点,这些技术对该领域的研究产生了重大影响,并对病理状态的进展有了深入的了解。本综述还强调了使用当前的成像技术和免疫细胞标记特异性示踪剂来识别和跟踪淋巴系统中的免疫细胞,这将有助于了解免疫治疗方案中的疾病进展和缓解。
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引用次数: 3
Hydrodynamic model for renal microvascular filtration: Effects of physiological and hemodynamic changes on glomerular size-selectivity 肾微血管滤过的流体动力学模型:生理和血流动力学变化对肾小球大小选择性的影响
IF 2.4 4区 医学 Q2 Medicine Pub Date : 2022-07-25 DOI: 10.1111/micc.12779
Numpong Punyaratabandhu, Panadda Dechadilok, Wannapong Triampo, Pisut Katavetin

Objective

The first step in renal urine formation is ultrafiltration across the glomerular barrier. The change in its nanostructure has been associated with nephrotic syndromes. Effects of physiological and hemodynamic factor alterations associated with diabetic nephropathy (DN) on glomerular permselectivity are examined through a mathematical model employing low-Reynolds-number hydrodynamics and hindered transport theory.

Methods

Glomerular capillaries are represented as networks of cylindrical tubes with multilayered walls. Glomerular basement membrane (GBM) is a fibrous medium with bimodal fiber sizes. Epithelial slit fiber spacing follows a lognormal distribution based on reported electron micrographs with the highest resolution. Endothelial fenestrae are filled with fibers the size of glycosaminoglycans (GAGs). Effects of fiber-macromolecule steric and hydrodynamic interactions are included. Focusing on diabetic nephropathy, the physiological and hemodynamic factors employed in the computation are those reported for healthy humans and patients with early-but-overt diabetic nephropathy. The macromolecule concentration is obtained as a finite element solution of the convection-diffusion equation.

Results

Computed sieving coefficients averaged along the capillary length agree well with ficoll sieving coefficients from studies in humans for most solute radii. GBM thickening and the loss of the slit diaphragm hardly affect glomerular permselectivity. GAG volume fraction reduction in the endothelial fenestrae, however, significantly increases macromolecule filtration. Increased renal plasma flow rate (RPF), glomerular hypertension, and reduction of lumen osmotic pressure cause a slight sieving coefficient decrease. These effects are amplified by an increased macromolecule size.

Conclusion

Our results indicate that glomerular hypertension and the reduction in the oncotic pressure decreases glomerular macromolecule filtration. Reduction of RPF and changes in the glomerular barrier structure associated with DN, however, increase the solute sieving. Damage to GAGs caused by hyperglycemia is likely to be the most prominent factor affecting glomerular size-selectivity.

目的肾尿形成的第一步是超滤过肾小球屏障。其纳米结构的变化与肾病综合征有关。通过采用低雷诺数流体动力学和阻碍转运理论的数学模型,研究了与糖尿病肾病(DN)相关的生理和血流动力学因子改变对肾小球过电选择性的影响。方法将肾小球毛细血管表示为具有多层壁的圆柱形管网络。肾小球基底膜(GBM)是一种纤维介质,具有双峰纤维大小。上皮狭缝纤维间距遵循对数正态分布,基于报道的电子显微图具有最高的分辨率。内皮窗内充满糖胺聚糖(GAGs)大小的纤维。包括纤维-大分子的空间和水动力相互作用的影响。针对糖尿病肾病,在计算中采用的生理和血流动力学因素是已报道的健康人和早期但明显的糖尿病肾病患者的生理和血流动力学因素。大分子浓度以对流扩散方程的有限元解的形式得到。结果沿毛细管长度计算的平均筛分系数与在大多数溶质半径的人类研究中得到的筛分系数吻合得很好。GBM增厚和狭缝膈的丧失几乎不影响肾小球的透性选择性。然而,内皮腔内GAG体积分数的降低显著增加了大分子滤过。肾血浆流速(RPF)升高、肾小球高血压和管腔渗透压降低导致筛分系数轻微降低。这些效应随着大分子大小的增加而被放大。结论肾小球高血压和肿瘤压降低可降低肾小球大分子滤过。然而,与DN相关的RPF减少和肾小球屏障结构的改变增加了溶质筛分。高血糖引起的gag损伤可能是影响肾小球大小选择性的最重要因素。
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引用次数: 1
Isolation and short-term culturing of primary lymphatic endothelial cells from collecting lymphatics: A techniques study 淋巴管原代淋巴内皮细胞的分离和短期培养:一项技术研究
IF 2.4 4区 医学 Q2 Medicine Pub Date : 2022-07-25 DOI: 10.1111/micc.12778
Kelli L. Jablon, Victoria L. Akerstrom, Min Li, Stephen E. Braun, Charles E. Norton, Jorge A. Castorena-Gonzalez

Objective

To develop an experimental method for routine isolation and short-term culture of primary lymphatic endothelial cells from specific collecting vessels.

Methods

Lymphatic endothelial cell tubes (LECTs) were isolated from micro-dissected collecting vessels. LECTs were allowed to attach and grow for ~3 weeks before being passaged. Non-purified cultures were partially characterized by immunofluorescence and RT-PCR at passages 1–2.

Results

The method was validated in cultures of primary lymphatic endothelial cells (LECs) from male and female mice. After 1 or 2 passages, >60% of the LECs maintained expression of Prox1. Expression of 22 different genes was assessed using RT-PCR. Prox1, Vegfr3, eNos, Cdh5, Pecam1, Cx43, Cx37, and Cx47, among others, were expressed in these short-term cultured LECs, while Myh11, Cnn1, Desmin, and Cd11b were not detected. Prox1 expression, as determined by western blotting, was similar in cultured LECs from age-matched male and female mice. Confocal imaging of intracellular calcium in cultures of primary LECs from Cdh5-GCaMP8 mice demonstrated that a functional phenotype was maintained, similar to lymphatic endothelial cells in freshly isolated vessels.

Conclusions

This method provides an innovative tool for routine isolation and study of primary LECs from specific collecting lymphatic vessels from any mouse, and in fact, from other species.

目的建立一种常规分离和短期培养淋巴内皮细胞的实验方法。方法从显微解剖的采集血管中分离淋巴内皮细胞管(LECTs)。让lts贴壁生长3周后传代。未纯化的培养物在1-2代通过免疫荧光和RT-PCR进行部分鉴定。结果该方法在雄性和雌性小鼠淋巴内皮细胞(LECs)培养中得到验证。1、2代后,60%的LECs保持Prox1的表达。RT-PCR检测22个不同基因的表达。短期培养的LECs中表达Prox1、Vegfr3、eNos、Cdh5、Pecam1、Cx43、Cx37、Cx47等,未检测到Myh11、Cnn1、Desmin、Cd11b等。通过western blotting检测,Prox1的表达在年龄匹配的雄性和雌性小鼠培养的LECs中相似。Cdh5-GCaMP8小鼠原代LECs细胞内钙的共聚焦成像表明,其功能表型与新分离血管中的淋巴内皮细胞相似。结论该方法为常规分离和研究小鼠及其他物种的特异性收集淋巴管的原代LECs提供了一种创新的工具。
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引用次数: 1
Perioperative trajectory of plasma viscosity: A prospective, observational, exploratory study in cardiac surgery 血浆粘度的围手术期轨迹:一项前瞻性、观察性、探索性的心脏外科研究
IF 2.4 4区 医学 Q2 Medicine Pub Date : 2022-07-15 DOI: 10.1111/micc.12777
Liana Valeanu, Stefan Andrei, Carmen Ginghina, Cornel Robu, Adrian Ciurciun, Cosmin Balan, Mihai Stefan, Anca Stoian, Iulia Stanculea, Andreea Cheta, Laura Dima, Ovidiu Stiru, Daniela Filipescu, Serban-Ion Bubenek-Turconi, Dan Longrois

Objective

Plasma viscosity is one of the critical factors that regulate microcirculatory flow but has received scant research attention. The main objective of this study was to evaluate plasma viscosity in cardiac surgery with respect to perioperative trajectory, main determinants, and impact on outcome.

Methods

Prospective, single center, observational study, including 50 adult patients undergoing cardiac surgery with cardiopulmonary bypass between February 1, 2020 and May 31, 2021. Clinical perioperative characteristics, short term outcome, standard blood analysis, plasma viscosity, total proteins, and fibrinogen concentrations were recorded at 10 distinct time points during the first perioperative week.

Results

The longitudinal analysis showed that plasma viscosity is strongly influenced by proteins and measurement time points. Plasma viscosity showed a coefficient of variation of 11.3 ± 1.08 for EDTA and 12.1 ± 2.1 for citrate, similarly to total proteins and hemoglobin, but significantly lower than fibrinogen (p < .001). Plasma viscosity had lower percentage changes compared to hemoglobin (RANOVA, p < .001), fibrinogen (RANOVA, p < .001), and total proteins (RANOVA, p < .001). The main determinant of plasma viscosity was protein concentrations. No association with outcome was found, but the study may have been underpowered to detect it.

Conclusion

Plasma viscosity had a low coefficient of variation and low perioperative changes, suggesting tight regulation. Studies linking plasma viscosity with outcome would require large patient cohorts.

目的血浆黏度是调节微循环血流的关键因素之一,但目前研究较少。本研究的主要目的是评估心脏手术中血浆粘度与围手术期轨迹、主要决定因素和对结果的影响。方法前瞻性、单中心、观察性研究,纳入2020年2月1日至2021年5月31日期间接受心脏手术合并体外循环的50例成年患者。在围手术期第一周的10个不同时间点记录临床围手术期特征、短期预后、标准血分析、血浆粘度、总蛋白和纤维蛋白原浓度。结果纵向分析表明,血浆粘度受蛋白质和测量时间点的影响较大。血浆粘度变化系数显示EDTA为11.3±1.08,柠檬酸盐为12.1±2.1,与总蛋白和血红蛋白相似,但显著低于纤维蛋白原(p < .001)。与血红蛋白(RANOVA, p < 0.001)、纤维蛋白原(RANOVA, p < 0.001)和总蛋白(RANOVA, p < 0.001)相比,血浆粘度的变化百分比较低。血浆粘度的主要决定因素是蛋白质浓度。没有发现与结果的联系,但这项研究可能没有足够的能力来检测它。结论血浆粘度变化系数小,围手术期变化小,有严密的调控。将血浆粘度与结果联系起来的研究需要大量的患者队列。
{"title":"Perioperative trajectory of plasma viscosity: A prospective, observational, exploratory study in cardiac surgery","authors":"Liana Valeanu,&nbsp;Stefan Andrei,&nbsp;Carmen Ginghina,&nbsp;Cornel Robu,&nbsp;Adrian Ciurciun,&nbsp;Cosmin Balan,&nbsp;Mihai Stefan,&nbsp;Anca Stoian,&nbsp;Iulia Stanculea,&nbsp;Andreea Cheta,&nbsp;Laura Dima,&nbsp;Ovidiu Stiru,&nbsp;Daniela Filipescu,&nbsp;Serban-Ion Bubenek-Turconi,&nbsp;Dan Longrois","doi":"10.1111/micc.12777","DOIUrl":"10.1111/micc.12777","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Plasma viscosity is one of the critical factors that regulate microcirculatory flow but has received scant research attention. The main objective of this study was to evaluate plasma viscosity in cardiac surgery with respect to perioperative trajectory, main determinants, and impact on outcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Prospective, single center, observational study, including 50 adult patients undergoing cardiac surgery with cardiopulmonary bypass between February 1, 2020 and May 31, 2021. Clinical perioperative characteristics, short term outcome, standard blood analysis, plasma viscosity, total proteins, and fibrinogen concentrations were recorded at 10 distinct time points during the first perioperative week.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The longitudinal analysis showed that plasma viscosity is strongly influenced by proteins and measurement time points. Plasma viscosity showed a coefficient of variation of 11.3 ± 1.08 for EDTA and 12.1 ± 2.1 for citrate, similarly to total proteins and hemoglobin, but significantly lower than fibrinogen (<i>p</i> &lt; .001). Plasma viscosity had lower percentage changes compared to hemoglobin (RANOVA, <i>p</i> &lt; .001), fibrinogen (RANOVA, <i>p</i> &lt; .001), and total proteins (RANOVA, <i>p</i> &lt; .001). The main determinant of plasma viscosity was protein concentrations. No association with outcome was found, but the study may have been underpowered to detect it.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Plasma viscosity had a low coefficient of variation and low perioperative changes, suggesting tight regulation. Studies linking plasma viscosity with outcome would require large patient cohorts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40524878","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: 3
期刊
Microcirculation
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