Microcirculation最新文献_第6页

Advanced glycated end-products inhibit dilation through constitutive endothelial RAGE and Nox1/4 in rat isolated skeletal muscle arteries 晚期糖基化终产物通过构成性内皮RAGE和Nox1/4抑制大鼠离体骨骼肌动脉的扩张。

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2023-11-20 DOI: 10.1111/micc.12837

Nadim Naser, Chenchel K. Lonj, Matthew Rikard-Bell, Shaun L. Sandow, Timothy V. Murphy

Objective

This study investigated the actions of advanced glycated end-products (AGE), their receptors (RAGE), and NAD(P)H oxidase (Nox) subtypes 1, 2, and 4 on mechanisms of endothelium-dependent dilation of the rat cremaster muscle artery (CMA).

Methods

Immunofluorescence studies were used to examine expression of RAGE in rat arteries. ROS accumulation was measured using luminescence and fluorescence assays. Functional studies were performed using pressure myography.

Results

High levels of RAGE expression were shown in the endothelial cells of the CMA, compared with low endothelial expression in middle cerebral and mesenteric arteries and the aorta. Exogenous AGE (in vitro glycated bovine serum albumin) stimulated H2O2 accumulation in CMA, which was prevented by the RAGE antagonist FPS-ZM1, the NAD(P)H oxidase (Nox) inhibitor apocynin and inhibited by the Nox1/4 inhibitor setanaxib, but not the Nox2 inhibitor GSK2795039. In functional studies, AGE inhibited vasodilation of CMA stimulated by acetylcholine, sodium nitroprusside, and the BKCa activator NS1619, but not adenosine-induced dilation. FPS-ZM1, apocynin, and setanaxib prevented the inhibitory effects of AGE on responses to acetylcholine and NS-1619.

Conclusion

These observations suggest RAGE are constitutively expressed in the endothelium of the rat CMA and may be activated by AGE to stimulate Nox1/4 and ROS formation with resulting inhibition of NO and BKCa-mediated endothelium-dependent dilation.

目的:研究晚期糖基化终产物(AGE)及其受体(RAGE)和NAD(P)H氧化酶(Nox)亚型1、2和4对大鼠肌动脉(CMA)内皮依赖性扩张的作用机制。方法:采用免疫荧光法检测RAGE在大鼠动脉组织中的表达。用发光和荧光法测定ROS积累。使用压力肌图进行功能研究。结果:RAGE在CMA内皮细胞中呈高表达，而在大脑中动脉、肠系膜动脉和主动脉中呈低表达。外源性AGE(体外糖化牛血清白蛋白)刺激CMA中H2O2的积累，RAGE拮抗剂FPS-ZM1和NAD(P)H氧化酶(Nox)抑制剂apocynin可以阻止H2O2的积累，Nox1/4抑制剂setanaxb可以抑制H2O2的积累，但Nox2抑制剂GSK2795039不能抑制H2O2的积累。在功能研究中，AGE抑制乙酰胆碱、硝普钠和BKCa激活剂NS1619刺激的CMA血管舒张，但不抑制腺苷诱导的舒张。FPS-ZM1、罗布麻素和西他那西可阻止AGE对乙酰胆碱和NS-1619的抑制作用。结论:RAGE在大鼠CMA的内皮中组成性表达，并可能被AGE激活，刺激Nox1/4和ROS的形成，从而抑制NO和bkca介导的内皮依赖性扩张。

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引用次数: 0

Vascular persistence following precision micropuncture 精密微穿刺后的血管持久性。

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2023-11-10 DOI: 10.1111/micc.12835

Summer N. Horchler, Patrick C. Hancock, Mingjie Sun, Alexander T. Liu, Sameer Massand, Jessica C. El-Mallah, Dana Goldenberg, Olivia Waldron, Mary E. Landmesser, Shailaja Agrawal, Srinivas V. Koduru, Dino J. Ravnic

Objective

The success of engineered tissues continues to be limited by time to vascularization and perfusion. Recently, we described a simple microsurgical approach, termed micropuncture (MP), which could be used to rapidly vascularize an adjacently placed scaffold from the recipient macrovasculature. Here we studied the long-term persistence of the MP-induced microvasculature.

Methods

Segmental 60 μm diameter MPs were created in the recipient rat femoral artery and vein followed by coverage with a simple Type 1 collagen scaffold. The recipient vasculature and scaffold were then wrapped en bloc with a silicone sheet to isolate intrinsic vascularization. Scaffolds were harvested at 28 days post-implantation for detailed analysis, including using a novel artificial intelligence (AI) approach.

Results

MP scaffolds demonstrated a sustained increase of vascular density compared to internal non-MP control scaffolds (p < 0.05) secondary to increases in both vessel diameters (p < 0.05) and branch counts (p < 0.05). MP scaffolds also demonstrated statistically significant increases in red blood cell (RBC) perfused lumens.

Conclusions

This study further highlights that the intrinsic MP-induced vasculature continues to persist long-term. Its combination of rapid and stable angiogenesis represents a novel surgical platform for engineered scaffold and graft perfusion.

目的：工程组织的成功仍然受到血管化和灌注时间的限制。最近，我们描述了一种简单的显微外科方法，称为微穿刺（MP），可用于从受体大血管系统快速为相邻放置的支架提供血管。在这里，我们研究了MP诱导的微血管的长期持续性。方法：Segmental 60 在受体大鼠股动脉和静脉中产生直径为μm的MP，然后用简单的1型胶原支架覆盖。然后用硅胶片整体包裹受体血管系统和支架，以分离内在血管形成。脚手架于28日收割植入后几天进行详细分析，包括使用新型人工智能（AI）方法。结果：与内部非MP对照支架相比，MP支架显示出血管密度的持续增加（p 结论：这项研究进一步强调了MP诱导的固有血管系统继续长期存在。它结合了快速和稳定的血管生成，为工程支架和移植物灌注提供了一种新的手术平台。

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引用次数: 0

Vascular polycystin proteins in health and disease 血管性多囊蛋白在健康和疾病中的作用。

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2023-10-12 DOI: 10.1111/micc.12834

Ulrich C. Mbiakop, Jonathan H. Jaggar

PKD1 (polycystin 1) and PKD2 (polycystin 2) are expressed in a variety of different cell types, including arterial smooth muscle and endothelial cells. PKD1 is a transmembrane domain protein with a large extracellular N-terminus that is proposed to act as a mechanosensor and receptor. PKD2 is a member of the transient receptor potential (TRP) channel superfamily which is also termed TRPP1. Mutations in the genes which encode PKD1 and PKD2 lead to autosomal dominant polycystic kidney disease (ADPKD). ADPKD is one of the most prevalent monogenic disorders in humans and is associated with extrarenal and vascular complications, including hypertension. Recent studies have uncovered mechanisms of activation and physiological functions of PKD1 and PKD2 in arterial smooth muscle and endothelial cells. It has also been found that PKD function is altered in the vasculature during ADPKD and hypertension. We will summarize this work and discuss future possibilities for this area of research.

PKD1（多囊蛋白1）和PKD2（多囊蛋白2）在多种不同的细胞类型中表达，包括动脉平滑肌和内皮细胞。PKD1是一种跨膜结构域蛋白，具有大的细胞外N末端，被认为是一种机械传感器和受体。PKD2是瞬时受体电位（TRP）通道超家族的成员，也称为TRPP1。编码PKD1和PKD2的基因突变导致常染色体多囊肾病（ADPKD）。ADPKD是人类最常见的单基因疾病之一，与肾外和血管并发症有关，包括高血压。最近的研究揭示了PKD1和PKD2在动脉平滑肌和内皮细胞中的激活机制和生理功能。还发现，在ADPKD和高血压期间，血管系统中的PKD功能发生改变。我们将总结这项工作，并讨论这一研究领域未来的可能性。

引用次数: 0

The effect of sepsis and reactive oxygen species on skeletal muscle interstitial oxygen pressure during contractions 败血症和活性氧对收缩过程中骨骼肌间质氧压的影响。

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2023-10-06 DOI: 10.1111/micc.12833

Naoki Hitosugi, Kazuki Hotta, Yoshikazu Taketa, Ren Takamizawa, Yutaka Fujii, Ryo Ikegami, Hajime Tamiya, Tatsuro Inoue, Atsuhiro Tsubaki

Objective

This study aims to examine the effect of sepsis on the dynamics of skeletal muscle partial oxygen pressure during muscle contractions as well as the effect of reactive oxygen species (ROS) scavenger (ascorbic acid, Asc).

Methods

Twenty-seven male Sprague–Dawley rats (2–3 months old) were randomly assigned to three groups; sham, cecal ligation and puncture (CLP), or CLP plus ascorbic acid treatment group (CLP + Asc). Electrical stimuli-induced muscle contractions and partial oxygen pressure measurements were performed at 3 h after CLP. The interstitial oxygen pressure (PO₂is) in the spinotrapezius muscle was measured by the phosphorescence quenching method.

Results

The PO₂is at rest was not different between the three groups. The PO₂is decreased from rest to contraction in all groups. Compared to the sham, the time to decrease PO₂is was significantly faster in CLP but not in CLP + Asc (p < .05). Compared to the sham, the PO₂is during muscle contractions was significantly lower in both CLP and CLP + Asc (p < .05, respectively).

Conclusions

Our results suggest that CLP-induced sepsis accelerated the decay of PO₂is at the onset of muscle contractions and maintained a low level of PO₂is during muscle contractions.

目的：本研究旨在探讨败血症对肌肉收缩过程中骨骼肌氧分压动力学的影响以及活性氧清除剂（抗坏血酸，Asc）的影响。方法：27只雄性Sprague-Dawley大鼠（2-3只）月龄）随机分为三组；假手术、盲肠结扎穿刺（CLP）或CLP加抗坏血酸治疗组（CLP + Asc）。电刺激引起的肌肉收缩和氧分压测量在3 CLP后h。用磷光猝灭法测定了脊髓斜方肌间质氧压。结果：三组患者PO2静息状态差异无统计学意义。在所有组中，PO2从静止到收缩都有所下降。与假手术相比，CLP中降低PO2 is的时间明显更快，但CLP中没有 + Asc（p 在CLP和CLP的肌肉收缩过程中，2 is显著降低 + Asc（p 结论：我们的研究结果表明，CLP诱导的败血症在肌肉收缩开始时加速了PO2-is的衰变，并在肌肉收缩期间保持了低水平的PO2-is。

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引用次数: 0

The role of glycosaminoglycans in blood pressure regulation 糖胺聚糖在血压调节中的作用。

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2023-10-04 DOI: 10.1111/micc.12832

Baris Afsar, Rengin Elsurer Afsar

Essential hypertension (HT) is the global health problem and is a major risk factor for the development of cardiovascular and kidney disease. High salt intake has been associated with HT and impaired kidney sodium excretion is considered to be a major mechanism for the development of HT. Although kidney has a very important role in regulation of BP, this traditional view of BP regulation was challenged by recent findings suggesting that nonosmotic tissue sodium deposition is very important for BP regulation. This new paradigm indicates that sodium can be stored and deposited nonosmotically in the interstitium without water retention and without increased BP. One of the major determinants of this deposition is glycosaminoglycans (GAGs). By binding to GAGs found in the endothelial surface layer (ESL) which contains glycocalyx, sodium is osmotically inactivated and not induce concurrent water retention. Thus, GAGs has important function for homeostatic BP and sodium regulation. In the current review, we summarized the role of GAGs in ESL and BP regulation.

原发性高血压（HT）是全球健康问题，也是心血管和肾脏疾病发展的主要危险因素。高盐摄入与HT有关，肾脏钠排泄受损被认为是HT发展的主要机制。尽管肾脏在调节血压方面发挥着非常重要的作用，但最近的研究结果表明，非吸烟组织钠沉积对血压调节非常重要，这对传统的血压调节观点提出了挑战。这一新范式表明，钠可以非烟雾状地储存和沉积在间质中，而不会保持水分，也不会增加血压。这种沉积的主要决定因素之一是糖胺聚糖（GAGs）。通过与内皮表面层（ESL）中发现的GAG结合，钠被渗透失活，不会诱导同时的水滞留。因此，GAGs在稳态血压和钠调节方面具有重要作用。在目前的综述中，我们总结了GAG在ESL和BP调节中的作用。

引用次数: 0

Arf6 is required for endocytosis and filamentous actin assembly during angiogenesis in vitro 在体外血管生成过程中，Arf6是内吞作用和丝状肌动蛋白组装所必需的。

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2023-09-26 DOI: 10.1111/micc.12831

Caitlin R. Francis, Makenzie L. Bell, Marina M. Skripnichuk, Erich J. Kushner

Objective

Endocytosis is a process vital to angiogenesis and vascular homeostasis. In pathologies where supraphysiological growth factor signaling underlies disease etiology, such as in diabetic retinopathy and solid tumors, strategies to limit chronic growth factor signaling by way of blunting endocytic processes have been shown to have tremendous clinical value. ADP ribosylation factor 6 (Arf6) is a small GTPase that promotes the assembly of actin necessary for clathrin-mediated and clathrin-independent endocytosis. In its absence, growth factor signaling is greatly diminished, which has been shown to ameliorate pathological signaling input in diseased vasculature. However, it is less clear if there are bystander effects related to loss of Arf6 on angiogenic behaviors. Our goal was to provide an analysis of Arf6's function in angiogenic endothelium, focusing on its role in actin and endocytosis as well as sprouting morphogenesis.

Methods

Primary endothelial cells were cultured in both 2D and 3D environments. Here, endothelial cells were fixed and stained for various proteins or transfected with fluorescently-tagged constructs for live-cell imaging.

Results

We found that Arf6 localized to both filamentous actin and sites of endocytosis in two-dimensional culture. Loss of Arf6 distorted both apicobasal polarity and reduced the total cellular filamentous actin content, which may be the primary driver underlying gross sprouting dysmorphogenesis in its absence.

Conclusions

Our findings highlight that endothelial Arf6 is a potent mediator of both actin regulation and endocytosis and is required for proper sprout formation.

目的：细胞内积是一个对血管生成和血管稳态至关重要的过程。在超生理生长因子信号传导是疾病病因的病理学中，如糖尿病视网膜病变和实体瘤，通过钝化内吞过程来限制慢性生长因子信号的策略已被证明具有巨大的临床价值。ADP核糖基化因子6（Arf6）是一种小的GTP酶，它促进网格蛋白介导和网格蛋白非依赖性内吞所必需的肌动蛋白的组装。在缺乏生长因子的情况下，生长因子信号传导大大减少，这已被证明可以改善病变血管系统中的病理信号传导输入。然而，目前尚不清楚是否存在与Arf6缺失有关的旁观者对血管生成行为的影响。我们的目标是分析Arf6在血管生成内皮中的功能，重点分析其在肌动蛋白和内吞作用以及发芽形态发生中的作用。方法：在2D和3D环境中培养原代内皮细胞。在此，将内皮细胞固定并染色各种蛋白质，或用荧光标记的构建体转染以进行活细胞成像。结果：我们发现在二维培养中，Arf6定位于丝状肌动蛋白和内吞位点。Arf6的缺失扭曲了尖鼻极性，并降低了细胞丝状肌动蛋白的总含量，这可能是在缺乏其的情况下导致毛芽畸形发生的主要驱动因素。结论：我们的研究结果强调，内皮Arf6是肌动蛋白调节和内吞作用的有效介质，是正常芽形成所必需的。

{"title":"Arf6 is required for endocytosis and filamentous actin assembly during angiogenesis in vitro","authors":"Caitlin R. Francis, Makenzie L. Bell, Marina M. Skripnichuk, Erich J. Kushner","doi":"10.1111/micc.12831","DOIUrl":"10.1111/micc.12831","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Endocytosis is a process vital to angiogenesis and vascular homeostasis. In pathologies where supraphysiological growth factor signaling underlies disease etiology, such as in diabetic retinopathy and solid tumors, strategies to limit chronic growth factor signaling by way of blunting endocytic processes have been shown to have tremendous clinical value. ADP ribosylation factor 6 (Arf6) is a small GTPase that promotes the assembly of actin necessary for clathrin-mediated and clathrin-independent endocytosis. In its absence, growth factor signaling is greatly diminished, which has been shown to ameliorate pathological signaling input in diseased vasculature. However, it is less clear if there are bystander effects related to loss of Arf6 on angiogenic behaviors. Our goal was to provide an analysis of Arf6's function in angiogenic endothelium, focusing on its role in actin and endocytosis as well as sprouting morphogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Primary endothelial cells were cultured in both 2D and 3D environments. Here, endothelial cells were fixed and stained for various proteins or transfected with fluorescently-tagged constructs for live-cell imaging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that Arf6 localized to both filamentous actin and sites of endocytosis in two-dimensional culture. Loss of Arf6 distorted both apicobasal polarity and reduced the total cellular filamentous actin content, which may be the primary driver underlying gross sprouting dysmorphogenesis in its absence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings highlight that endothelial Arf6 is a potent mediator of both actin regulation and endocytosis and is required for proper sprout formation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 8","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41134265","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: 1

Estimation of shear stress heterogeneity along capillary segments in angiogenic rat mesenteric microvascular networks 血管生成大鼠肠系膜微血管网络毛细血管段剪切应力异质性的估计。

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2023-09-09 DOI: 10.1111/micc.12830

Nien-Wen Hu, Banks M. Lomel, Elijah W. Rice, Mir Md Nasim Hossain, Malisa Sarntinoranont, Timothy W. Secomb, Walter L. Murfee, Peter Balogh

Objective

Fluid shear stress is thought to be a regulator of endothelial cell behavior during angiogenesis. The link, however, requires an understanding of stress values at the capillary level in angiogenic microvascular networks. Critical questions remain. What are the stresses? Do capillaries experience similar stress magnitudes? Can variations explain vessel-specific behavior? The objective of this study was to estimate segment-specific shear stresses in angiogenic networks.

Methods

Images of angiogenic networks characterized by increased vascular density were obtained from rat mesenteric tissues stimulated by compound 48/80-induced mast cell degranulation. Vessels were identified by perfusion of a 40 kDa fixable dextran prior to harvesting and immunolabeling for PECAM. Using a network flow-based segment model with physiologically relevant parameters, stresses were computed per vessel for regions across multiple networks.

Results

Stresses ranged from 0.003 to 2328.1 dyne/cm² and varied dramatically at the capillary level. For all regions, the maximum segmental shear stresses were for capillary segments. Stresses along proximal capillaries branching from arteriole inlets were increased compared to stresses along capillaries in more distal regions.

Conclusions

The results highlight the variability of shear stresses along angiogenic capillaries and motivate new discussions on how endothelial cells may respond in vivo to segment-specific microenvironment during angiogenesis.

目的：流体剪切应力被认为是血管生成过程中内皮细胞行为的调节因子。然而，这种联系需要了解血管生成微血管网络中毛细血管水平的应力值。关键问题仍然存在。压力是什么？毛细血管是否经历类似的应力大小？变异能解释船只的特定行为吗？本研究的目的是估计血管生成网络中的节段特异性剪切应力。方法：从化合物48/80诱导的肥大细胞脱颗粒刺激的大鼠肠系膜组织中获得以血管密度增加为特征的血管生成网络的图像。通过灌注40 kDa可固定的右旋糖酐。使用具有生理相关参数的基于网络流的分段模型，计算多个网络中每个血管的应力。结果：应力范围为0.003至2328.1 达因/cm2，并且在毛细管水平上显著变化。对于所有区域，毛细管段的最大节段剪切应力。与更远端区域的毛细管应力相比，从小动脉入口分支的近端毛细管应力增加。结论：该结果突出了血管生成毛细血管剪切应力的可变性，并激发了关于内皮细胞在血管生成过程中如何在体内对节段特异性微环境做出反应的新讨论。

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引用次数: 0

The association between hypoalbuminemia and microcirculation, endothelium, and glycocalyx disorders in children with sepsis 脓毒症患儿低白蛋白血症与微循环、内皮和糖萼紊乱的关系

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2023-08-28 DOI: 10.1111/micc.12829

Jaime Fernández-Sarmiento, Ricardo Hernández-Sarmiento, María Paula Salazar, Sofia Barrera, Valeria Castilla, Catalina Duque

Objective

The objective of this study was to evaluate the association between serum albumin levels and microcirculation changes, glycocalyx degradation, and the clinical outcomes of interest.

Methods

Observational, prospective study in children with sepsis. The primary outcome was the association between hypoalbuminemia and microcirculation disorders, endothelial activation and glycocalyx degradation using a perfused boundary region (PBR) (abnormal >2.0 μm on sublingual video microscopy) or plasma biomarkers (syndecan-1, angiopoietin-2).

Results

A total of 125 patients with sepsis were included. The median age was 2.0 years (IQR 0.5–12.5). Children with hypoalbuminemia had more abnormal microcirculation with a higher PBR (2.16 μm [IQR 2.03–2.47] vs. 1.92 [1.76–2.28]; p = .01) and more 4–6 μm capillaries recruited (60% vs. 40%; p = .04). The low albumin group that had the worst PBR had the most 4–6 μm capillaries recruited (rho 0.29; p < .01), 48% higher Ang-2 (p = .04), worse annexin A5 (p = 0.03) and no syndecan-1 abnormalities (p = .21). Children with hypoalbuminemia and a greater percentage of blood volume in their capillaries needed mechanical ventilation more often (56.3% vs. 43.7%; aOR 2.01 95% CI 1.38–3.10: p < .01).

Conclusions

In children with sepsis, an association was found between hypoalbuminemia and microcirculation changes, vascular permeability, and greater endothelial glycocalyx degradation.

目的：本研究的目的是评估血清白蛋白水平与微循环变化、糖盏降解和感兴趣的临床结果之间的关系。方法：对儿童败血症进行前瞻性观察研究。主要结果是低白蛋白血症与微循环障碍、内皮细胞活化和使用灌注边界区（PBR）的糖盏降解之间的相关性（异常>2.0 μm）或血浆生物标志物（syndecan-1，angiopoietin-2）。结果：共纳入125例败血症患者。中位年龄为2.0岁年（IQR 0.5-12.5）。患有低白蛋白血症的儿童微循环异常较多，PBR较高（2.16 μm[IQR 2.03-2.47]对1.92[1.76-2.28]；p = .01）及更多4-6 μm毛细血管被吸收（60%对40%；p = .04）。PBR最差的低白蛋白组有最多的4-6 μm毛细血管募集（rho 0.29；p 结论：在败血症儿童中，发现低白蛋白血症与微循环变化、血管通透性和内皮糖盏降解增加有关。

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引用次数: 0

Three-dimensional spatial quantitative analysis of cardiac lymphatics in the mouse heart 小鼠心脏淋巴管的三维空间定量分析。

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2023-08-22 DOI: 10.1111/micc.12826

Evan H. Phillips, Vytautas P. Bindokas, Dahee Jung, Jay Teamer, Jan K. Kitajewski, R. John Solaro, Beata M. Wolska, Steve Seung-Young Lee

Objective

Three-dimensional (3D) microscopy and image data analysis are necessary for studying the morphology of cardiac lymphatic vessels (LyVs) and their association with other cell types. We aimed to develop a methodology for 3D multiplexed lightsheet microscopy and highly sensitive and quantitative image analysis to identify pathological remodeling in the 3D morphology of LyVs in young adult mouse hearts with familial hypertrophic cardiomyopathy (HCM).

Methods

We developed a 3D lightsheet microscopy workflow providing a quick turn-around (as few as 5–6 days), multiplex fluorescence detection, and preservation of LyV structure and epitope markers. Hearts from non-transgenic and transgenic (TG) HCM mice were arrested in diastole, retrograde perfused, immunolabeled, optically cleared, and imaged. We built an image-processing pipeline to quantify LyV morphological parameters at the chamber and branch levels.

Results

Chamber-specific pathological alterations of LyVs were identified, and significant changes were seen in the right atrium (RA). TG hearts had a higher volume percent of ER-TR7⁺ fibroblasts and reticular fibers. In the RA, we found associations between ER-TR7⁺ volume percent and both LyV segment density and median diameter.

Conclusions

This workflow and study enabled multi-scale analysis of pathological changes in cardiac LyVs of young adult mice, inviting ideas for research on LyVs in cardiac disease.

目的：三维（3D）显微镜和图像数据分析对于研究心脏淋巴管的形态及其与其他细胞类型的关系是必要的。我们旨在开发一种3D多重光片显微镜和高灵敏度和定量图像分析的方法，以确定患有家族性肥厚型心肌病（HCM）的年轻成年小鼠心脏中LyVs的3D形态的病理重塑天），多重荧光检测，以及LyV结构和表位标记物的保存。来自非转基因和转基因（TG）HCM小鼠的心脏在舒张期被捕获、逆行灌注、免疫标记、光学清除和成像。我们建立了一个图像处理管道来量化腔和分支水平上的LyV形态参数。结果：发现了LyVs的室特异性病理改变，右心房（RA）发生了显著变化。TG心脏具有较高体积百分比的ER-TR7+成纤维细胞和网状纤维。在RA中，我们发现ER-TR7+体积百分比与LyV节段密度和中值直径之间存在关联。结论：该工作流程和研究能够对年轻成年小鼠心脏LyVs的病理变化进行多尺度分析，为LyVs在心脏病中的研究提供了思路。

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引用次数: 1

Progress in molecular mechanisms of coronary microvascular dysfunction 冠状动脉微血管功能障碍的分子机制研究进展。

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2023-08-22 DOI: 10.1111/micc.12827

Hao Li, Yuping Gao, Yuanyuan Lin

Coronary microvascular dysfunction is a high-risk factor for many cardiovascular events. However, because of multiple risk factors and limited understanding about its underlying pathophysiological mechanisms, it was easily misdiagnosed. Therefore, its clinical diagnosis and treatment were greatly restricted. Coronary microcirculation refers to microvessels that play an important role in the physiological regulation of myocardial perfusion and regulating blood flow distribution, fulfilling myocardial metabolic needs and moderating peripheral vascular resistance. In coronary microvascular dysfunction, vascular endothelial celldamage is a critical link. The main feature of early coronary microvascular dysfunction is the impairment of endothelial cell proliferation, adhesion, migration, apoptosis, and secretion. Moreover, coronary microvascular dysfunction risk factors include hyperglycemia, lipid metabolism disorders, ischemia-reperfusion injury, aging, and hypertension, similar to coronary atherosclerosis. There are various mechanisms by which these risk factors harm endothelial function and cause microcirculatory disturbances. Therefore, we reviewed coronary microvascular dysfunction's risk factors and pathogenesis in this article.

冠状动脉微血管功能障碍是许多心血管事件的高危因素。然而，由于多种危险因素和对其潜在病理生理机制的了解有限，它很容易被误诊。因此，其临床诊断和治疗受到很大限制。冠状动脉微循环是指在生理调节心肌灌注、调节血流分布、满足心肌代谢需求和调节外周血管阻力方面发挥重要作用的微血管。在冠状动脉微血管功能障碍中，血管内皮细胞损伤是一个关键环节。早期冠状动脉微血管功能障碍的主要特征是内皮细胞增殖、粘附、迁移、凋亡和分泌受损。此外，冠状动脉微血管功能障碍的危险因素包括高血糖、脂质代谢紊乱、缺血再灌注损伤、衰老和高血压，类似于冠状动脉粥样硬化。这些危险因素损害内皮功能并引起微循环障碍的机制多种多样。因此，本文就冠状动脉微血管功能障碍的危险因素及发病机制进行综述。

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引用次数: 0