Microcirculation最新文献_第10页

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 Q3 HEMATOLOGY

Microcirculation

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 Q3 HEMATOLOGY

Microcirculation

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 Q3 HEMATOLOGY

Microcirculation

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 Q3 HEMATOLOGY

Microcirculation

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 Q3 HEMATOLOGY

Microcirculation

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。

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引用次数: 3

Photoacoustic imaging for microcirculation 用于微循环的光声成像

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2022-07-06 DOI: 10.1111/micc.12776

Shubham Mirg, Kevin L. Turner, Haoyang Chen, Patrick J. Drew, Sri-Rajasekhar Kothapalli

Microcirculation facilitates the blood-tissue exchange of nutrients and regulates blood perfusion. It is, therefore, essential in maintaining tissue health. Aberrations in microcirculation are potentially indicative of underlying cardiovascular and metabolic pathologies. Thus, quantitative information about it is of great clinical relevance. Photoacoustic imaging (PAI) is a capable technique that relies on the generation of imaging contrast via the absorption of light and can image at micron-scale resolution. PAI is especially desirable to map microvasculature as hemoglobin strongly absorbs light and can generate a photoacoustic signal. This paper reviews the current state of the art for imaging microvascular networks using photoacoustic imaging. We further describe how quantitative information about blood dynamics such as the total hemoglobin concentration, oxygen saturation, and blood flow rate is obtained using PAI. We also discuss its importance in understanding key pathophysiological processes in neurovascular, cardiovascular, ophthalmic, and cancer research fields. We then discuss the current challenges and limitations of PAI and the approaches that can help overcome these limitations. Finally, we provide the reader with an overview of future trends in the field of PAI for imaging microcirculation.

微循环促进血液组织交换营养物质，调节血液灌注。因此，它对维持组织健康是必不可少的。微循环异常可能表明潜在的心血管和代谢疾病。因此，关于它的定量信息具有重要的临床意义。光声成像(PAI)是一种依靠光吸收产生成像对比度并能以微米级分辨率成像的技术。PAI特别适合用于绘制微血管图，因为血红蛋白强烈吸收光并能产生光声信号。本文综述了利用光声成像技术对微血管网络进行成像的最新进展。我们进一步描述了如何定量信息的血液动力学，如总血红蛋白浓度，血氧饱和度和血流速率是如何使用PAI获得的。我们还讨论了它在理解神经血管、心血管、眼科和癌症研究领域的关键病理生理过程中的重要性。然后，我们讨论了PAI当前面临的挑战和局限性，以及有助于克服这些局限性的方法。最后，我们向读者概述了PAI成像微循环领域的未来趋势。

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引用次数: 5

Effect of the snake venom component crotamine on lymphatic endothelial cell responses and lymph transport 蛇毒成分克罗胺对淋巴内皮细胞反应和淋巴运输的影响

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2022-06-11 DOI: 10.1111/micc.12775

Hongjiang Si, Chunhiu Yin, Wei Wang, Peter Davies, Elda Sanchez, Montamas Suntravat, David Zawieja, Walter Cromer

Objective

The pathology of snake envenomation is closely tied to the severity of edema in the tissue surrounding the area of the bite. Elucidating the mechanisms that promote the development of such severe edema is critical to a better understanding of how to treat this life-threatening injury. We focused on one of the most abundant venom components in North American viper venom, crotamine, and the effects it has on the cells and function of the lymphatic system.

Methods

We used RT-PCR to identify the location and relative abundance of crotamine's cellular targets (Kvα channels) within the tissues and cells of the lymphatic system. We used calcium flux, nitrate production, and cell morphometry to determine the effects of crotamine on lymphatic endothelial cells. We used tracer transport, node morphometry, and node deposition to determine the effects of crotamine on lymph transport in vivo.

Results

We found that genes that encode targets of crotamine are highly present in lymphatic tissues and cells and that there is a differential distribution of those genes that correlates with phasic contractile activity. We found that crotamine potentiates calcium flux in human dermal lymphatic endothelial cells in response to stimulation with histamine and sheer stress (but not alone) and that it alters the production of nitric oxide in response to shear as well as changes the level of F-actin polymerization of those same cells. Crotamine alters lymphatic transport of large molecular weight tracers to local lymph nodes and is deposited within the node mostly in the immediate subcapsular region.

Conclusion

This evidence suggests that snake venom components may have an impact on the function of the lymphatic system. This needs to be studied in greater detail as there are numerous venom components that may have effects on aspects of the lymphatic system. This would not only provide basic information on the pathobiology of snakebite but also provide targets for improved therapeutics to treat snakebite.

目的蛇中毒的病理与被咬部位周围组织水肿的严重程度密切相关。阐明促进这种严重水肿发展的机制对于更好地理解如何治疗这种危及生命的损伤至关重要。我们专注于北美毒蛇毒液中最丰富的毒液成分之一，克罗胺，以及它对淋巴系统细胞和功能的影响。方法利用RT-PCR技术鉴定了克罗米胺的细胞靶点(Kvα通道)在淋巴系统组织和细胞中的位置和相对丰度。我们使用钙通量、硝酸盐生成和细胞形态测定法来确定克罗米胺对淋巴内皮细胞的影响。我们使用示踪剂运输、淋巴结形态测定和淋巴结沉积来确定克罗米胺对体内淋巴运输的影响。结果我们发现，在淋巴组织和细胞中，编码克罗米胺靶标的基因大量存在，并且这些基因与相收缩活性相关的分布存在差异。我们发现，在组胺和纯应激刺激下(但不是单独的)，克罗米胺增强了人真皮淋巴内皮细胞中的钙通量，并改变了对剪切反应的一氧化氮的产生，以及改变了这些细胞的f -肌动蛋白聚合水平。克罗米胺改变大分子量示踪剂到局部淋巴结的淋巴运输，并在淋巴结内沉积，主要在紧邻的包膜下区域。结论蛇毒成分可能对淋巴系统功能有影响。这需要更详细地研究，因为有许多毒液成分可能对淋巴系统的各个方面产生影响。这不仅为蛇咬伤的病理生物学提供了基本信息，而且为改进蛇咬伤的治疗方法提供了靶点。

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引用次数: 5

Endothelial cell membrane cholesterol content regulates the contribution of TRPV4 channels in ACh-induced vasodilation in rat gracilis arteries 内皮细胞膜胆固醇含量调节TRPV4通道在乙酰胆碱诱导大鼠股薄动脉血管舒张中的作用

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2022-06-11 DOI: 10.1111/micc.12774

Emily E. Morin, Sophia Salbato, Benjimen R. Walker, Jay S. Naik

Objective

Our previous work demonstrated that endothelial cell (EC) membrane cholesterol is reduced following 48 h of chronic hypoxia (CH). CH couples endothelial transient receptor potential subfamily V member 4 (TRPV4) channels to muscarinic receptor signaling through an endothelium-dependent hyperpolarization (EDH) pathway does not present in control animals. TRVPV4 channel activity has been shown to be regulated by membrane cholesterol. Hence, we hypothesize that acute manipulation of endothelial cell membrane cholesterol inversely determines the contribution of TRPV4 channels to endothelium-dependent vasodilation.

Methods

Male Sprague–Dawley rats were exposed to ambient atmospheric (atm.) pressure or 48-h of hypoxia (0.5 atm). Vasodilation to acetylcholine (ACh) was determined using pressure myography in gracilis arteries. EC membrane cholesterol was depleted using methyl-β-cyclodextrin (MβCD) and supplemented with MβCD-cholesterol.

Results

Inhibiting TRPV4 did not affect ACh-induced vasodilation in normoxic controls. However, TRPV4 inhibition reduced resting diameter in control arteries suggesting basal activity. TRPV4 contributes to ACh-induced vasodilation in these arteries when EC membrane cholesterol is depleted. Inhibiting TRPV4 attenuated ACh-induced vasodilation in arteries from CH animals that exhibit lower EC membrane cholesterol than normoxic controls. EC cholesterol repletion in arteries from CH animals abolished the contribution of TRPV4 to ACh-induced vasodilation.

Conclusion

Endothelial cell membrane cholesterol impedes the contribution of TRPV4 channels in EDH-mediated dilation. These results provide additional evidence for the importance of plasma membrane cholesterol content in regulating intracellular signaling and vascular function.

目的我们之前的研究表明，慢性缺氧(CH) 48小时后内皮细胞(EC)膜胆固醇降低。CH偶联内皮瞬时受体电位亚家族V成员4 (TRPV4)通道通过内皮依赖性超极化(EDH)途径传递毒毒碱受体信号，在对照动物中不存在。TRVPV4通道活性已被证明受膜胆固醇调节。因此，我们假设内皮细胞膜胆固醇的急性操纵与TRPV4通道对内皮依赖性血管舒张的贡献相反。方法雄性Sprague-Dawley大鼠暴露于环境大气压(atm)或缺氧48 h (0.5 atm)。用压力肌图测定股薄肌动脉对乙酰胆碱(ACh)的血管舒张。用甲基β-环糊精(m -β- cd)去除EC膜胆固醇，并添加m -β cd -胆固醇。结果抑制TRPV4对乙酰胆碱所致的血管舒张无影响。然而，TRPV4抑制降低了对照动脉的静息直径，提示基础活性。当EC膜胆固醇耗尽时，TRPV4有助于乙酰胆碱诱导的这些动脉血管舒张。抑制TRPV4可减弱乙酰胆碱诱导的动脉血管舒张，这些动物的EC膜胆固醇低于正常氧合对照组。CH动物动脉中EC胆固醇的补充消除了TRPV4对乙酰胆碱诱导的血管舒张的作用。结论内皮细胞膜胆固醇阻碍了TRPV4通道在edh介导的扩张中的作用。这些结果为质膜胆固醇含量在调节细胞内信号和血管功能中的重要性提供了额外的证据。

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引用次数: 1

Retinal vascular profile in predicting incident cardiometabolic diseases among individuals with diabetes 视网膜血管特征预测糖尿病患者心血管代谢疾病的发生

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2022-06-02 DOI: 10.1111/micc.12772

Bjorn Kaijun Betzler, Charumathi Sabanayagam, Yih-Chung Tham, Carol Y. Cheung, Ching-Yu Cheng, Tien-Yin Wong, Simon Nusinovici

Objective

To determine the longitudinal associations between retinal vascular profile (RVP) and four major cardiometabolic diseases; and to quantify the predictive improvements when adding RVP beyond traditional risk factors in individuals with diabetes.

Methods

Subjects were enrolled from the Singapore Epidemiology of Eye Disease (SEED) study, a multi-ethnic population-based cohort. Four incident cardiometabolic diseases, calculated over a ~ 6-year period, were considered: cardiovascular disease (CVD), hypertension (HTN), diabetic kidney disease (DKD), and hyperlipidemia (HLD). The RVP—vessel tortuosity, branching angle, branching coefficient, fractal dimension, vessel caliber, and DR status—was characterized at baseline using a computer-assisted program. Traditional risk factors at baseline included age, gender, ethnicity, smoking, blood pressure (BP), HbA1c, estimated glomerular filtration rate (eGFR), or cholesterol. The improvements in predictive performance when adding RVP (compared with only traditional risk factors) was calculated using several metrics including area under the receiver operating characteristics curve (AUC) and net reclassification improvement (NRI).

Results

Among 1770 individuals with diabetes, incidences were 6.3% (n = 79/1259) for CVD, 48.7% (n = 166/341) for HTN, 14.6% (n = 175/1199) for DKD, and 59.4% (n = 336/566) for HLD. DR preceded the onset of CVD (RR 1.85[1.14;3.00]) and DKD (1.44 [1.06;1.96]). Narrower arteriolar caliber preceding the onset of HTN (0.84 [0.72;0.99]), and changes in arteriolar branching angle preceded the onset of CVD (0.78 [0.62;0.98]) and HTN (1.15 [1.03;1.29]). The largest predictive improvement was found for HTN with AUC increment of 3.4% (p = .027) and better reclassification of 11.4% of the cases and 4.6% of the controls (p = .008).

Conclusion

We found that RVPs improved the prediction of HTN in individuals with diabetes, but add limited information for CVD, DKD, and HLD predictions.

目的探讨视网膜血管剖面(RVP)与四种主要心脏代谢疾病的纵向关系;并量化在糖尿病患者中添加RVP超出传统风险因素时的预测性改善。方法从新加坡眼病流行病学(SEED)研究中招募受试者，这是一项基于多民族人群的队列研究。在6年的时间里，我们考虑了四种突发的心脏代谢疾病:心血管疾病(CVD)、高血压(HTN)、糖尿病肾病(DKD)和高脂血症(HLD)。rvp(血管弯曲度、分支角度、分支系数、分形维数、血管口径和DR状态)在基线时使用计算机辅助程序进行表征。传统的基线危险因素包括年龄、性别、种族、吸烟、血压(BP)、糖化血红蛋白(HbA1c)、肾小球滤过率(eGFR)或胆固醇。当添加RVP时(与仅使用传统风险因素相比)，预测性能的改善使用几个指标进行计算，包括受试者工作特征曲线下面积(AUC)和净重分类改善(NRI)。结果在1770例糖尿病患者中，CVD患病率为6.3% (n = 79/1259)， HTN患病率为48.7% (n = 166/341)， DKD患病率为14.6% (n = 175/1199)， HLD患病率为59.4% (n = 336/566)。DR先于CVD发生(RR为1.85[1.14;3.00])，DKD为1.44[1.06;1.96])。小动脉口径变窄先于HTN(0.84[0.72;0.99])，小动脉分支角度的改变先于CVD(0.78[0.62;0.98])和HTN(1.15[1.03;1.29])的发生。HTN的预测改善最大，AUC增加3.4% (p = 0.027)， 11.4%的病例和4.6%的对照组的重新分类得到改善(p = 0.008)。结论:我们发现RVPs改善了糖尿病患者HTN的预测，但对CVD、DKD和HLD的预测增加了有限的信息。

{"title":"Retinal vascular profile in predicting incident cardiometabolic diseases among individuals with diabetes","authors":"Bjorn Kaijun Betzler, Charumathi Sabanayagam, Yih-Chung Tham, Carol Y. Cheung, Ching-Yu Cheng, Tien-Yin Wong, Simon Nusinovici","doi":"10.1111/micc.12772","DOIUrl":"10.1111/micc.12772","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To determine the longitudinal associations between retinal vascular profile (RVP) and four major cardiometabolic diseases; and to quantify the predictive improvements when adding RVP beyond traditional risk factors in individuals with diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Subjects were enrolled from the Singapore Epidemiology of Eye Disease (SEED) study, a multi-ethnic population-based cohort. Four incident cardiometabolic diseases, calculated over a ~ 6-year period, were considered: cardiovascular disease (CVD), hypertension (HTN), diabetic kidney disease (DKD), and hyperlipidemia (HLD). The RVP—vessel tortuosity, branching angle, branching coefficient, fractal dimension, vessel caliber, and DR status—was characterized at baseline using a computer-assisted program. Traditional risk factors at baseline included age, gender, ethnicity, smoking, blood pressure (BP), HbA1c, estimated glomerular filtration rate (eGFR), or cholesterol. The improvements in predictive performance when adding RVP (compared with only traditional risk factors) was calculated using several metrics including area under the receiver operating characteristics curve (AUC) and net reclassification improvement (NRI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 1770 individuals with diabetes, incidences were 6.3% (<i>n</i> = 79/1259) for CVD, 48.7% (<i>n</i> = 166/341) for HTN, 14.6% (<i>n</i> = 175/1199) for DKD, and 59.4% (<i>n</i> = 336/566) for HLD. DR preceded the onset of CVD (RR 1.85[1.14;3.00]) and DKD (1.44 [1.06;1.96]). Narrower arteriolar caliber preceding the onset of HTN (0.84 [0.72;0.99]), and changes in arteriolar branching angle preceded the onset of CVD (0.78 [0.62;0.98]) and HTN (1.15 [1.03;1.29]). The largest predictive improvement was found for HTN with AUC increment of 3.4% (<i>p</i> = .027) and better reclassification of 11.4% of the cases and 4.6% of the controls (<i>p</i> = .008).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We found that RVPs improved the prediction of HTN in individuals with diabetes, but add limited information for CVD, DKD, and HLD predictions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"29 4-5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42758678","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

Peripheral endothelial and microvascular damage in liver cirrhosis: A systematic review and meta-analysis 肝硬化外周内皮和微血管损伤:一项系统综述和荟萃分析

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2022-06-02 DOI: 10.1111/micc.12773

Ioanna Papagiouvanni, Marieta P. Theodorakopoulou, Pantelis A. Sarafidis, Emmanouil Sinakos, Ioannis Goulis

Objective

This is the first systematic review and meta-analysis of studies using any available functional method to examine differences in peripheral endothelial function between cirrhotic and non-cirrhotic individuals.

Methods

Literature search involved PubMed, Web-of-Science, and Scopus databases, as well as gray literature sources. We included studies in adult subjects evaluating endothelial function with any semi-invasive or non-invasive functional method in patients with and without liver cirrhosis.

Results

From 3378 records initially retrieved, 15 studies with a total of 570 participants were included in the final quantitative meta-analysis. In six studies examining endothelial function with flow-mediated-dilatation, no differences between patients with cirrhosis and controls were evident (WMD: 1.33, 95%CI [−2.87, 5.53], I² = 97%, p < .00001). Among studies assessing differences in endothelial-dependent or endothelial-independent vasodilation with venous-occlusion-plethysmography, there were no significant differences between the two groups. When pooling all studies together, regardless of the technique used, no significant difference in endothelial function between cirrhotic patients and controls was observed(SMD: 0.79, 95%CI[−0.04, 1.63], I² = 94%, p < .00001).

Conclusions

No differences in peripheral endothelial function assessed with semi-invasive or non-invasive functional methods exist between cirrhotic and non-cirrhotic subjects. The increasing co-existence of cardiovascular risk factors leading to impaired vascular reactivity in cirrhotic patients may partly explain these findings.

目的:这是第一个系统回顾和荟萃分析的研究，使用任何可用的功能方法来检查肝硬化和非肝硬化患者外周血管内皮功能的差异。方法文献检索包括PubMed、Web-of-Science、Scopus等数据库以及灰色文献。我们纳入了成人受试者的研究，用任何半侵入性或非侵入性功能方法评估有或无肝硬化患者的内皮功能。从最初检索的3378份记录中，最终的定量荟萃分析纳入了15项研究，共570名参与者。在6项通过血流介导的扩张检查内皮功能的研究中，肝硬化患者与对照组之间无明显差异(WMD: 1.33, 95%CI [- 2.87, 5.53]， I2 = 97%， p < 0.00001)。在评估内皮依赖性或内皮非依赖性血管舒张与静脉闭塞容积描记术的差异的研究中，两组之间没有显著差异。当将所有研究合并在一起时，无论使用何种技术，肝硬化患者和对照组之间的内皮功能没有显著差异(SMD: 0.79, 95%CI[- 0.04, 1.63]， I2 = 94%， p < 0.00001)。结论:采用半侵入性或非侵入性功能方法评估的肝硬化和非肝硬化患者外周血管内皮功能无差异。导致肝硬化患者血管反应性受损的心血管危险因素的增加共存可能部分解释了这些发现。

{"title":"Peripheral endothelial and microvascular damage in liver cirrhosis: A systematic review and meta-analysis","authors":"Ioanna Papagiouvanni, Marieta P. Theodorakopoulou, Pantelis A. Sarafidis, Emmanouil Sinakos, Ioannis Goulis","doi":"10.1111/micc.12773","DOIUrl":"10.1111/micc.12773","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This is the first systematic review and meta-analysis of studies using any available functional method to examine differences in peripheral endothelial function between cirrhotic and non-cirrhotic individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Literature search involved PubMed, Web-of-Science, and Scopus databases, as well as gray literature sources. We included studies in adult subjects evaluating endothelial function with any semi-invasive or non-invasive functional method in patients with and without liver cirrhosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From 3378 records initially retrieved, 15 studies with a total of 570 participants were included in the final quantitative meta-analysis. In six studies examining endothelial function with flow-mediated-dilatation, no differences between patients with cirrhosis and controls were evident (WMD: 1.33, 95%CI [−2.87, 5.53], <i>I</i><sup>2</sup> = 97%, <i>p</i> < .00001). Among studies assessing differences in endothelial-dependent or endothelial-independent vasodilation with venous-occlusion-plethysmography, there were no significant differences between the two groups. When pooling all studies together, regardless of the technique used, no significant difference in endothelial function between cirrhotic patients and controls was observed(SMD: 0.79, 95%CI[−0.04, 1.63], <i>I</i><sup>2</sup> = 94%, <i>p</i> < .00001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>No differences in peripheral endothelial function assessed with semi-invasive or non-invasive functional methods exist between cirrhotic and non-cirrhotic subjects. The increasing co-existence of cardiovascular risk factors leading to impaired vascular reactivity in cirrhotic patients may partly explain these findings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"29 4-5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42149471","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