Microcirculation最新文献_第5页

Regulation of BzATP-Induced Blood–Brain Barrier Endothelial Cell Hyperpermeability by NLRP3 Inflammasome Inhibition 通过抑制NLRP3炎性体调节bzatp诱导的血脑屏障内皮细胞高通透性

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2025-03-07 DOI: 10.1111/micc.70006

Aliyah Anderson, O'lisa Yaa Waithe, Gabriela Seplovich, Oluwatoyin Olagunju, Christlyn Greene, Amrendra Singh, Saravanakumar Muthusamy, Binu Tharakan

Objective

The blood–brain barrier (BBB) is a semi-permeable microvascular barrier, composed of endothelial cells conjoined by tight junction proteins. Following pathological conditions, i.e., traumatic brain injury (TBI), BBB dysfunction occurs, leading to microvascular hyperpermeability, resulting in cerebral edema formation and elevated intracranial pressure. Recent evidence suggests that the activation of pro-inflammatory signaling pathways is critical to BBB dysfunction. The NLRP3 inflammasome has been implicated as a key component of pro-inflammatory signaling. The aim of this study was to determine the upstream regulators of NLRP3 inflammasome activation that cause subsequent BBB aberration and microvascular hyperpermeability.

Methods

Brain microvascular endothelial cells were exposed to benzoyl ATP (BzATP) with or without MCC950. We employed immunocytochemical localization of tight junction proteins, fluorometric enzymatic assays, total gene expression analyses of ZO-1, and monolayer permeability studies to assess the effect of BzATP-induced injury on NLRP3 inflammasome activation/inhibition.

Results

BzATP treatment induced monolayer hyperpermeability and increased caspase-1 and MMP-9 activities. NLRP3 inhibition decreased caspase-1 and MMP-9 activities and rescued BzATP-induced monolayer permeability significantly.

Conclusions

NLRP3 inflammasome signaling is critical to BBB endothelial cell dysfunction. Extracellular ATP is an upstream promoter of BBB hyperpermeability. NLRP3 inflammasome activation leads to subsequent caspase-1 and MMP-9-mediated tight junction protein disarray.

目的血脑屏障（BBB）是一种半渗透性微血管屏障，由内皮细胞和紧密连接蛋白组成。在创伤性脑损伤（TBI）等病理情况下，血脑屏障会出现功能障碍，导致微血管高渗透性，从而形成脑水肿和颅内压升高。最近的证据表明，促炎信号通路的激活对 BBB 功能障碍至关重要。NLRP3 炎性体被认为是促炎信号传导的关键组成部分。本研究的目的是确定 NLRP3 炎性体激活的上游调节因子，这些因子会导致随后的 BBB 畸变和微血管高渗透性。方法将脑微血管内皮细胞暴露于含有或不含 MCC950 的苯甲酰 ATP（BzATP）中。我们采用紧密连接蛋白免疫细胞化学定位、荧光酶测定、ZO-1 总基因表达分析和单层渗透性研究来评估 BzATP 诱导的损伤对 NLRP3 炎症小体激活/抑制的影响。结果 BzATP 处理诱导单层渗透性增高，并增加了 caspase-1 和 MMP-9 的活性。抑制 NLRP3 可降低 caspase-1 和 MMP-9 的活性，并显著缓解 BzATP 诱导的单层渗透性。结论 NLRP3炎性体信号对 BBB 内皮细胞功能障碍至关重要。细胞外 ATP 是 BBB 高渗透性的上游促进因子。NLRP3 炎性体的激活会导致随后由 caspase-1 和 MMP-9 介导的紧密连接蛋白混乱。

{"title":"Regulation of BzATP-Induced Blood–Brain Barrier Endothelial Cell Hyperpermeability by NLRP3 Inflammasome Inhibition","authors":"Aliyah Anderson, O'lisa Yaa Waithe, Gabriela Seplovich, Oluwatoyin Olagunju, Christlyn Greene, Amrendra Singh, Saravanakumar Muthusamy, Binu Tharakan","doi":"10.1111/micc.70006","DOIUrl":"https://doi.org/10.1111/micc.70006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The blood–brain barrier (BBB) is a semi-permeable microvascular barrier, composed of endothelial cells conjoined by tight junction proteins. Following pathological conditions, i.e., traumatic brain injury (TBI), BBB dysfunction occurs, leading to microvascular hyperpermeability, resulting in cerebral edema formation and elevated intracranial pressure. Recent evidence suggests that the activation of pro-inflammatory signaling pathways is critical to BBB dysfunction. The NLRP3 inflammasome has been implicated as a key component of pro-inflammatory signaling. The aim of this study was to determine the upstream regulators of NLRP3 inflammasome activation that cause subsequent BBB aberration and microvascular hyperpermeability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Brain microvascular endothelial cells were exposed to benzoyl ATP (BzATP) with or without MCC950. We employed immunocytochemical localization of tight junction proteins, fluorometric enzymatic assays, total gene expression analyses of ZO-1, and monolayer permeability studies to assess the effect of BzATP-induced injury on NLRP3 inflammasome activation/inhibition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>BzATP treatment induced monolayer hyperpermeability and increased caspase-1 and MMP-9 activities. NLRP3 inhibition decreased caspase-1 and MMP-9 activities and rescued BzATP-induced monolayer permeability significantly.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>NLRP3 inflammasome signaling is critical to BBB endothelial cell dysfunction. Extracellular ATP is an upstream promoter of BBB hyperpermeability. NLRP3 inflammasome activation leads to subsequent caspase-1 and MMP-9-mediated tight junction protein disarray.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 3","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571407","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

Hyperspectral Imaging in the Healing Prognosis of Diabetes Related Foot Ulcers. A Systematic Review and Meta-Analysis 高光谱成像在糖尿病相关足溃疡愈合预后中的作用。系统回顾和荟萃分析

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2025-03-05 DOI: 10.1111/micc.70005

Patricia M. González-Villacorta, Mateo López-Moral, Marta García-Madrid, Esther García-Morales, Aroa Tardáguila-García, José Luis Lázaro-Martínez

Objective

The diagnostic capability of hyperspectral (HSI) imaging has been focused on the prognosis of wound healing in patients with peripheral artery disease and diabetic foot ulcers (DFUs). The aim of this study was to evaluate the performance characteristics of HSI to determine the pretest probability for the prognosis of DFU healing.

Methods

A systematic search was performed on the PubMed, Medline, and Cochrane databases to identify studies evaluating HSI in predicting the prognosis of DFUs. This study was registered with PROSPERO (CRD42023495391). All selected studies were evaluated using the STROBE guidelines to assess the reporting quality for observational studies. Meta-DiSc software was used to analyze the collected data.

Results

Nine publications (142 participants) were evaluated for systematic review. The meta-analysis included four publications examining the prospective diagnostic capability of HSI. Concerning the prognostic accuracy of HSI, it had a pooled sensitivity of 0.84 (0.75–0.9) and a specificity of 0.79 (0.66–0.88) for predicting DFU healing, as well as an odds ratio of 20.4, resulting in a positive likelihood ratio of 4.1 and a negative likelihood ratio of 0.2 (heterogeneity I² = 0).

Conclusions

The meta-analysis revealed promising prognostic capability of HSI for the healing of DFU. More randomized clinical trials need to be published as our results are based on only prospective and comparative studies.

目的研究高光谱（HSI）成像对外周动脉病变合并糖尿病足溃疡（DFUs）患者伤口愈合的预后。本研究的目的是评估HSI的表现特征，以确定DFU愈合预后的预测概率。方法对PubMed、Medline和Cochrane数据库进行系统检索，以确定评估HSI预测DFUs预后的研究。本研究已在PROSPERO注册（CRD42023495391）。所有选择的研究都使用STROBE指南进行评估，以评估观察性研究的报告质量。Meta-DiSc软件对收集的数据进行分析。结果对9篇文献（142名受试者）进行系统评价。荟萃分析包括四篇研究HSI前瞻性诊断能力的出版物。关于HSI的预后准确性，预测DFU愈合的总敏感性为0.84(0.75-0.9)，特异性为0.79(0.66-0.88)，比值比为20.4，阳性似然比为4.1，阴性似然比为0.2（异质性I2 = 0）。结论荟萃分析显示HSI对DFU愈合具有良好的预后能力。由于我们的结果仅基于前瞻性和比较研究，因此需要发表更多的随机临床试验。

{"title":"Hyperspectral Imaging in the Healing Prognosis of Diabetes Related Foot Ulcers. A Systematic Review and Meta-Analysis","authors":"Patricia M. González-Villacorta, Mateo López-Moral, Marta García-Madrid, Esther García-Morales, Aroa Tardáguila-García, José Luis Lázaro-Martínez","doi":"10.1111/micc.70005","DOIUrl":"https://doi.org/10.1111/micc.70005","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The diagnostic capability of hyperspectral (HSI) imaging has been focused on the prognosis of wound healing in patients with peripheral artery disease and diabetic foot ulcers (DFUs). The aim of this study was to evaluate the performance characteristics of HSI to determine the pretest probability for the prognosis of DFU healing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic search was performed on the PubMed, Medline, and Cochrane databases to identify studies evaluating HSI in predicting the prognosis of DFUs. This study was registered with PROSPERO (CRD42023495391). All selected studies were evaluated using the STROBE guidelines to assess the reporting quality for observational studies. Meta-DiSc software was used to analyze the collected data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Nine publications (142 participants) were evaluated for systematic review. The meta-analysis included four publications examining the prospective diagnostic capability of HSI. Concerning the prognostic accuracy of HSI, it had a pooled sensitivity of 0.84 (0.75–0.9) and a specificity of 0.79 (0.66–0.88) for predicting DFU healing, as well as an odds ratio of 20.4, resulting in a positive likelihood ratio of 4.1 and a negative likelihood ratio of 0.2 (heterogeneity <i>I</i><sup>2</sup> = 0).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The meta-analysis revealed promising prognostic capability of HSI for the healing of DFU. More randomized clinical trials need to be published as our results are based on only prospective and comparative studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 3","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554408","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

Small Arteries From Old Spontaneously Hypertensive Rats Exhibit Enhanced Endothelium-Independent Vasodilatory Capacity and Reduced Stiffness 老年自发性高血压大鼠的小动脉表现出内皮不依赖性血管舒张能力增强和僵硬度降低

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2025-02-17 DOI: 10.1111/micc.70004

Francisco I. Ramirez-Perez, Thomas J. Jurrissen, Marc A. Augenreich, Jorge A. Castorena-Gonzalez, Mariana Morales-Quinones, Christopher A. Foote, Zahra Nourian, Olubodun M. Lateef, Natnicha Imkaew, Zhe Sun, Michael A. Hill, Gerald A. Meininger, Jaume Padilla, Luis A. Martinez-Lemus

Objective

In conduit arteries, aging and hypertension are associated with stiffening characterized by increased cytoskeletal F-actin and endothelial dysfunction. Herein, we determined if this also happens at the level of the resistance vasculature.

Methods

We retrospectively compared the mechanical and structural characteristics of small arteries isolated from older hypertensive and younger normotensive (64.7 ± 2.8 vs. 32.1 ± 1.9 years old) human subjects. The intersection of aging and hypertension was studied in small mesenteric arteries from old (88 weeks of age) spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) normotensive rats.

Results

Arteries from older hypertensive subjects were stiffer and had more F-actin, relative to those from younger normotensives. Comparatively, arteries from old SHRs showed reduced stiffness and increased vasodilation to sodium nitroprusside without changes in F-actin. Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) were increased in the SHR arteries and exposure of naive arteries to exogenous MMP-2 and MMP-9 augmented responsiveness to sodium nitroprusside and adenosine.

Conclusions

In conclusion, resistance arteries from old SHRs are softer and vasodilate more to exogenous nitric oxide than those of WKY rats. This improved endothelial-independent vasodilation is associated with an increased vascular expression of MMP-2 and MMP-9. We further conclude that aging and hypertension effects on the microcirculation may vary between species and vascular beds.

目的在导管动脉中，衰老和高血压与以细胞骨架f -肌动蛋白增加和内皮功能障碍为特征的硬化有关。在这里，我们确定这种情况是否也发生在阻力血管系统水平。方法回顾性比较老年高血压患者和年轻正常高血压患者（64.7±2.8岁vs. 32.1±1.9岁）分离的小动脉的力学和结构特征。在老龄（88周龄）自发性高血压（SHR）和Wistar Kyoto （WKY）正常大鼠的肠系膜小动脉中，研究了衰老与高血压的交叉关系。结果与年轻血压正常者相比，老年高血压患者的动脉更僵硬，f -肌动蛋白含量更高。相比之下，在硝普钠作用下，老年SHRs的动脉僵硬度降低，血管舒张度增加，但f -肌动蛋白没有变化。基质金属蛋白酶-2 （MMP-2）和-9 （MMP-9）在SHR动脉中升高，初始动脉暴露于外源性MMP-2和MMP-9增强了对硝普钠和腺苷的反应性。结论与WKY大鼠相比，老龄SHRs的阻力动脉更柔软，血管对外源性一氧化氮的舒张程度更高。这种内皮非依赖性血管舒张的改善与血管中MMP-2和MMP-9表达的增加有关。我们进一步得出结论，衰老和高血压对微循环的影响可能因物种和血管床而异。

{"title":"Small Arteries From Old Spontaneously Hypertensive Rats Exhibit Enhanced Endothelium-Independent Vasodilatory Capacity and Reduced Stiffness","authors":"Francisco I. Ramirez-Perez, Thomas J. Jurrissen, Marc A. Augenreich, Jorge A. Castorena-Gonzalez, Mariana Morales-Quinones, Christopher A. Foote, Zahra Nourian, Olubodun M. Lateef, Natnicha Imkaew, Zhe Sun, Michael A. Hill, Gerald A. Meininger, Jaume Padilla, Luis A. Martinez-Lemus","doi":"10.1111/micc.70004","DOIUrl":"https://doi.org/10.1111/micc.70004","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>In conduit arteries, aging and hypertension are associated with stiffening characterized by increased cytoskeletal F-actin and endothelial dysfunction. Herein, we determined if this also happens at the level of the resistance vasculature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively compared the mechanical and structural characteristics of small arteries isolated from older hypertensive and younger normotensive (64.7 ± 2.8 vs. 32.1 ± 1.9 years old) human subjects. The intersection of aging and hypertension was studied in small mesenteric arteries from old (88 weeks of age) spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) normotensive rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Arteries from older hypertensive subjects were stiffer and had more F-actin, relative to those from younger normotensives. Comparatively, arteries from old SHRs showed reduced stiffness and increased vasodilation to sodium nitroprusside without changes in F-actin. Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) were increased in the SHR arteries and exposure of naive arteries to exogenous MMP-2 and MMP-9 augmented responsiveness to sodium nitroprusside and adenosine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In conclusion, resistance arteries from old SHRs are softer and vasodilate more to exogenous nitric oxide than those of WKY rats. This improved endothelial-independent vasodilation is associated with an increased vascular expression of MMP-2 and MMP-9. We further conclude that aging and hypertension effects on the microcirculation may vary between species and vascular beds.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431137","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

Simulation of Conducted Responses in Microvascular Networks: Role of Gap Junction Current Rectification 微血管网络传导响应的模拟：缝隙结电流整流的作用

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2025-02-13 DOI: 10.1111/micc.70002

Sara Djurich, Grace V. Lee, Timothy W. Secomb

Objective

Local control of blood flow depends on signaling to arterioles via upstream conducted responses. Here, the objective is to examine how electrical properties of gap junctions between endothelial cells (EC) affect the spread of conducted responses in microvascular networks of the brain cortex, using a theoretical model based on EC electrophysiology.

Methods

Modeled EC currents are an inward-rectifying potassium current, a non-voltage-dependent potassium current, a leak current, and a gap junction current between adjacent ECs. Effects of varying gap junction conductance are considered, including asymmetric conductance, with higher conductance for forward currents (positive currents from upstream to downstream, based on blood flow direction). The response is initiated by a local increase in extracellular potassium concentration. The model is applied to a 45-segment synthetic network and a 4881-segment network from mouse brain cortex.

Results

The conducted response propagates preferentially to upstream arterioles when the conductance for forward currents is at least 20 times that for backward currents. The response depends strongly on the site of stimulation. With symmetric gap junction conductance, the network acts as a syncytium and the conducted response is dissipated.

Conclusions

Upstream propagation of conducted responses may depend on the asymmetric conductance of EC gap junctions.

目的局部血流控制依赖于通过上游传导反应向小动脉传递信号。本研究的目的是利用基于内皮细胞电生理学的理论模型，研究内皮细胞间隙连接的电特性如何影响大脑皮层微血管网络传导反应的传播。模拟的EC电流包括一个向内整流的钾电流、一个非电压依赖的钾电流、一个漏电流和一个相邻EC之间的间隙结电流。考虑了不同间隙结电导的影响，包括不对称电导，正向电流（基于血流方向从上游到下游的正电流）具有更高的电导。这种反应是由细胞外钾浓度的局部增加引起的。该模型应用于小鼠大脑皮层的45段合成网络和4881段网络。结果当正向电流的电导至少为反向电流的20倍时，传导响应优先向上游小动脉传播。这种反应很大程度上取决于刺激的部位。在对称间隙结电导率下，网络充当合胞体，传导响应被耗散。结论传导响应的上游传播可能取决于EC间隙连接的不对称电导。

{"title":"Simulation of Conducted Responses in Microvascular Networks: Role of Gap Junction Current Rectification","authors":"Sara Djurich, Grace V. Lee, Timothy W. Secomb","doi":"10.1111/micc.70002","DOIUrl":"https://doi.org/10.1111/micc.70002","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Local control of blood flow depends on signaling to arterioles via upstream conducted responses. Here, the objective is to examine how electrical properties of gap junctions between endothelial cells (EC) affect the spread of conducted responses in microvascular networks of the brain cortex, using a theoretical model based on EC electrophysiology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Modeled EC currents are an inward-rectifying potassium current, a non-voltage-dependent potassium current, a leak current, and a gap junction current between adjacent ECs. Effects of varying gap junction conductance are considered, including asymmetric conductance, with higher conductance for forward currents (positive currents from upstream to downstream, based on blood flow direction). The response is initiated by a local increase in extracellular potassium concentration. The model is applied to a 45-segment synthetic network and a 4881-segment network from mouse brain cortex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The conducted response propagates preferentially to upstream arterioles when the conductance for forward currents is at least 20 times that for backward currents. The response depends strongly on the site of stimulation. With symmetric gap junction conductance, the network acts as a syncytium and the conducted response is dissipated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Upstream propagation of conducted responses may depend on the asymmetric conductance of EC gap junctions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396892","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

Different Transcriptome Signatures of the Lymphatic and the Blood Vessels From Rat Mesentery Reveal Distinct Function Characteristics 大鼠肠系膜淋巴和血管的不同转录组特征揭示了不同的功能特征

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2025-02-13 DOI: 10.1111/micc.70003

Yumeng Jing, Jiayi Zhai, Min Gao, Xiu Xu, Zi-Gang Zhao, Zhen-Ao Zhao

Objective

Lymphatic vessels and blood vessels have some similarities in structure, but they have distinct contraction characteristics and functions. Revealing the detailed transcriptional differences of lymphatic, artery and vein are required for circulation research.

Methods

The tissues of the mesenteric lymphatic, artery, and vein were collected from Wistar rats. The transcriptome signatures of these tissues from RNA-seq (RNA sequencing) were analyzed using bioinformatic methods.

Results

GO (gene ontology) enrichment showed the three tissues have distinct gene expression patterns in extracellular matrix, cell adhesion molecule binding, receptor ligand activity, and contractile fiber. The genes involved in cell contractility were also differently expressed, which were enriched into the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways of cytoskeleton in muscle cells, vascular smooth muscle contraction, and renin-angiotensin system. Through PPI (protein–protein interaction) analysis, we identified 43 differently expressed hub genes in the three tissues. Thirty-four transcription factors and cofactors were identified as important for the normal function of the three tissues. Furthermore, we screened out 20 potential marker genes for each tissue.

Conclusions

Our study described the transcriptome signatures of mesenteric lymphatic, artery, and vein, shedding light on the distinct contraction mechanisms of these tissues. These results also provided potential therapeutic targets for circulation diseases and potential markers for lymphatic and blood vessel studies.

目的淋巴管与血管在结构上有一定的相似性，但其收缩特性和功能却截然不同。揭示淋巴、动脉和静脉的详细转录差异是循环研究的必要条件。方法取Wistar大鼠肠系膜淋巴、动脉、静脉组织。利用生物信息学方法分析了这些组织的RNA-seq （RNA测序）转录组特征。结果GO（基因本体）富集显示，三种组织在细胞外基质、细胞黏附分子结合、受体配体活性和收缩纤维等方面具有不同的基因表达模式。参与细胞收缩的基因也有不同的表达，这些基因富集在肌肉细胞细胞骨架、血管平滑肌收缩和肾素-血管紧张素系统的KEGG （Kyoto Encyclopedia of genes and Genomes）通路中。通过蛋白-蛋白相互作用（PPI）分析，我们在三种组织中鉴定出43个不同表达的枢纽基因。鉴定出34种转录因子和辅助因子对三种组织的正常功能有重要作用。此外，我们为每个组织筛选了20个潜在的标记基因。我们的研究描述了肠系膜淋巴、动脉和静脉的转录组特征，揭示了这些组织不同的收缩机制。这些结果也为循环疾病提供了潜在的治疗靶点，并为淋巴和血管研究提供了潜在的标志物。

{"title":"Different Transcriptome Signatures of the Lymphatic and the Blood Vessels From Rat Mesentery Reveal Distinct Function Characteristics","authors":"Yumeng Jing, Jiayi Zhai, Min Gao, Xiu Xu, Zi-Gang Zhao, Zhen-Ao Zhao","doi":"10.1111/micc.70003","DOIUrl":"https://doi.org/10.1111/micc.70003","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Lymphatic vessels and blood vessels have some similarities in structure, but they have distinct contraction characteristics and functions. Revealing the detailed transcriptional differences of lymphatic, artery and vein are required for circulation research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The tissues of the mesenteric lymphatic, artery, and vein were collected from Wistar rats. The transcriptome signatures of these tissues from RNA-seq (RNA sequencing) were analyzed using bioinformatic methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>GO (gene ontology) enrichment showed the three tissues have distinct gene expression patterns in extracellular matrix, cell adhesion molecule binding, receptor ligand activity, and contractile fiber. The genes involved in cell contractility were also differently expressed, which were enriched into the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways of cytoskeleton in muscle cells, vascular smooth muscle contraction, and renin-angiotensin system. Through PPI (protein–protein interaction) analysis, we identified 43 differently expressed hub genes in the three tissues. Thirty-four transcription factors and cofactors were identified as important for the normal function of the three tissues. Furthermore, we screened out 20 potential marker genes for each tissue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study described the transcriptome signatures of mesenteric lymphatic, artery, and vein, shedding light on the distinct contraction mechanisms of these tissues. These results also provided potential therapeutic targets for circulation diseases and potential markers for lymphatic and blood vessel studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396893","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

Combining In Vivo Two-Photon and Laser Speckle Microscopy With the Ex Vivo Capillary-Parenchymal Arteriole Preparation as a Novel Approach to Study Neurovascular Coupling 结合体内双光子和激光散斑显微镜与离体毛细血管-实质小动脉制备作为研究神经血管耦合的新方法。

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2025-01-07 DOI: 10.1111/micc.70001

Lowri E. Evans, Anna L. Gray, Katy R. Walsh, Thea G. E. Danby, Harry A. T. Pritchard, Stuart M. Allan, Alison M. Gurney, Adam S. Greenstein, Ingo Schiessl

Objective

Cerebral blood flow (CBF) decline is increasingly recognized as an area of importance for targeting neurodegenerative disorders, yet full understanding of the mechanisms that underlie CBF changes are lacking. Animal models are crucial for expanding our knowledge as methods for studying global CBF and neurovascular coupling in humans are limited and require expensive specialized scanners.

Methods

Use of appropriate animal models can increase our understanding of cerebrovascular function, so we have combined chronic cranial windows with in vivo two-photon and laser speckle microscopy and ex vivo capillary-parenchymal arteriole (CaPA) preparations. Chronic cranial windows allow for longitudinal direct observation of the cerebral microvasculature and surrounding parenchyma while the CaPA preparation can assess capillary and arteriole function in isolation of the neuronal tissue.

Results

Here, we found that extra-dural cranial windows and related imaging protocols do not affect vascular function in the CaPA preparation. Cortical vessels from animals that have undergone imaging can therefore be taken to discover physiological alterations in the cerebral vasculature that contribute to any observed in vivo changes.

Conclusion

This approach will enhance neurodegenerative research with the benefit of limiting animal usage.

目的：脑血流量（CBF）下降越来越被认为是针对神经退行性疾病的一个重要领域，但对CBF变化背后的机制还缺乏充分的了解。动物模型对于扩大我们的知识至关重要，因为研究人类整体脑血流和神经血管耦合的方法有限，并且需要昂贵的专业扫描仪。方法：采用合适的动物模型可以增加我们对脑血管功能的认识，因此我们将慢性颅窗与体内双光子和激光散斑显微镜以及离体毛细血管实质小动脉（CaPA）制备相结合。慢性颅窗允许纵向直接观察大脑微血管和周围实质，而CaPA制备可以在分离的神经元组织中评估毛细血管和小动脉的功能。结果：我们发现硬膜外颅窗和相关成像方案不影响CaPA制备中的血管功能。因此，通过对动物皮质血管进行成像，可以发现导致任何观察到的体内变化的脑血管系统的生理改变。结论：该方法将加强神经退行性疾病的研究，并有利于限制动物的使用。

{"title":"Combining In Vivo Two-Photon and Laser Speckle Microscopy With the Ex Vivo Capillary-Parenchymal Arteriole Preparation as a Novel Approach to Study Neurovascular Coupling","authors":"Lowri E. Evans, Anna L. Gray, Katy R. Walsh, Thea G. E. Danby, Harry A. T. Pritchard, Stuart M. Allan, Alison M. Gurney, Adam S. Greenstein, Ingo Schiessl","doi":"10.1111/micc.70001","DOIUrl":"10.1111/micc.70001","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Cerebral blood flow (CBF) decline is increasingly recognized as an area of importance for targeting neurodegenerative disorders, yet full understanding of the mechanisms that underlie CBF changes are lacking. Animal models are crucial for expanding our knowledge as methods for studying global CBF and neurovascular coupling in humans are limited and require expensive specialized scanners.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Use of appropriate animal models can increase our understanding of cerebrovascular function, so we have combined chronic cranial windows with in vivo two-photon and laser speckle microscopy and ex vivo capillary-parenchymal arteriole (CaPA) preparations. Chronic cranial windows allow for longitudinal direct observation of the cerebral microvasculature and surrounding parenchyma while the CaPA preparation can assess capillary and arteriole function in isolation of the neuronal tissue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Here, we found that extra-dural cranial windows and related imaging protocols do not affect vascular function in the CaPA preparation. Cortical vessels from animals that have undergone imaging can therefore be taken to discover physiological alterations in the cerebral vasculature that contribute to any observed in vivo changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This approach will enhance neurodegenerative research with the benefit of limiting animal usage.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951309","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: 0

Genetic Insights Into Coronary Microvascular Disease 冠状动脉微血管疾病的遗传学研究。

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2025-01-04 DOI: 10.1111/micc.12896

Nicole Wayne, Venkata S. Singamneni, Rasika Venkatesh, Tess Cherlin, Shefali S. Verma, Marie A. Guerraty

Coronary microvascular disease (CMVD) affects the coronary pre-arterioles, arterioles, and capillaries and can lead to blood supply–demand mismatch and cardiac ischemia. CMVD can present clinically as ischemia or myocardial infarction with no obstructive coronary arteries (INOCA or MINOCA, respectively). Currently, therapeutic options for CMVD are limited, and there are no targeted therapies. Genetic studies have emerged as an important tool to gain rapid insights into the molecular mechanisms of human diseases. For example, coronary artery disease (CAD) genome-wide association studies (GWAS) have enrolled hundreds of thousands of patients and have identified > 320 loci, elucidating CAD pathogenic pathways and helping to identify therapeutic targets. Here, we review the current landscape of genetic studies of CMVD, consisting mostly of genotype-first approaches. We then present the hypothesis that CAD GWAS have enrolled heterogenous populations and may be better characterized as ischemic heart disease (IHD) GWAS. We discuss how several of the genetic loci currently associated with CAD may be involved in the pathogenesis of CMVD. Genetic studies could help accelerate progress in understanding CMVD pathophysiology and identifying putative therapeutic targets. Larger phenotype-first genomic studies into CMVD with adequate sex and ancestry representation are needed. Given the extensive CAD genetic and functional validation data, future research should leverage these loci as springboards for CMVD genomic research.

冠状动脉微血管疾病（CMVD）影响冠状动脉前细动脉、小动脉和毛细血管，可导致血液供需不匹配和心脏缺血。CMVD在临床上表现为缺血或心肌梗死，无冠状动脉梗阻性（分别为INOCA或MINOCA）。目前，CMVD的治疗选择是有限的，并且没有靶向治疗。遗传研究已成为快速了解人类疾病分子机制的重要工具。例如，冠状动脉疾病（CAD）全基因组关联研究（GWAS）已经招募了数十万患者，并确定了bbbb320个位点，阐明了CAD的致病途径并帮助确定了治疗靶点。在这里，我们回顾了目前CMVD遗传研究的现状，主要包括基因型优先的方法。然后，我们提出假设，CAD GWAS已纳入异质人群，可能更好地表征为缺血性心脏病（IHD） GWAS。我们讨论了目前与CAD相关的几个基因位点如何参与CMVD的发病机制。遗传学研究可以帮助加速理解CMVD病理生理和确定假定的治疗靶点的进展。需要对CMVD进行更大规模的表型优先基因组研究，并具有足够的性别和血统代表性。鉴于广泛的CAD遗传和功能验证数据，未来的研究应该利用这些位点作为CMVD基因组研究的跳板。

{"title":"Genetic Insights Into Coronary Microvascular Disease","authors":"Nicole Wayne, Venkata S. Singamneni, Rasika Venkatesh, Tess Cherlin, Shefali S. Verma, Marie A. Guerraty","doi":"10.1111/micc.12896","DOIUrl":"10.1111/micc.12896","url":null,"abstract":"<p>Coronary microvascular disease (CMVD) affects the coronary pre-arterioles, arterioles, and capillaries and can lead to blood supply–demand mismatch and cardiac ischemia. CMVD can present clinically as ischemia or myocardial infarction with no obstructive coronary arteries (INOCA or MINOCA, respectively). Currently, therapeutic options for CMVD are limited, and there are no targeted therapies. Genetic studies have emerged as an important tool to gain rapid insights into the molecular mechanisms of human diseases. For example, coronary artery disease (CAD) genome-wide association studies (GWAS) have enrolled hundreds of thousands of patients and have identified > 320 loci, elucidating CAD pathogenic pathways and helping to identify therapeutic targets. Here, we review the current landscape of genetic studies of CMVD, consisting mostly of genotype-first approaches. We then present the hypothesis that CAD GWAS have enrolled heterogenous populations and may be better characterized as ischemic heart disease (IHD) GWAS. We discuss how several of the genetic loci currently associated with CAD may be involved in the pathogenesis of CMVD. Genetic studies could help accelerate progress in understanding CMVD pathophysiology and identifying putative therapeutic targets. Larger phenotype-first genomic studies into CMVD with adequate sex and ancestry representation are needed. Given the extensive CAD genetic and functional validation data, future research should leverage these loci as springboards for CMVD genomic research.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12896","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926953","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: 0

Colocalization of Ellipsoid Zone Disruption With Capillary Nonperfusion in Different Retinal Vascular Layers and Choriocapillaris on En Face OCT of Diabetic Patients 糖尿病患者不同视网膜血管层和绒毛膜毛细血管毛细血管非灌注时椭球区破坏的共定位。

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2024-12-27 DOI: 10.1111/micc.70000

Reza Mirshahi, Amir Rahdar, Mohamad Javad Ahmadi, Kaveh Fadakar, Ali Torkashvand, Shahbaz Nekoozadeh, Khalil Ghasemi Falavarjani

Purpose

To assess the colocalization of ellipsoid zone (EZ) disruption with nonperfusion in choriocapillaris (CC), retinal superficial capillary plexus (SCP), and deep capillary plexus (DCP) in diabetic patients using en face optical coherence tomography (OCT) and OCT angiography (OCTA).

Methods

Macular OCT and OCTA scans (3 × 3 mm) of 41 patients with diabetic retinopathy were obtained using an RTVue XR Avanti instrument. After correcting the shadow artifacts, EZ integrity was assessed in the en face OCT slab using the Gaussian mixture model clustering method compared with the corresponding EZ en face OCT of 11 age-matched normal patients. A similar technique was used for detecting capillary nonperfusion using CC en face OCTA. Geometric perfusion density (GPD) maps were also generated for the SCP and DCP. Maps of capillary nonperfusion in the CC, SCP, and DCP were compared pixel by pixel with the map generated from EZ disruption.

Results

Twenty-one patients with diabetic macular edema (DME) and 20 patients with diabetic retinopathy without macular edema were included in this study. In both groups, the overlap of EZ disruption was significantly greater with choriocapillaris nonperfusion than with nonperfusion in the SCP and DCP (dry macular group: 33.15% with CC vs. 0.46% with SCP vs. 1.70% with DCP, p < 0.001; DME group: 29.81% with CC vs. 1.22% with SCP vs. 6.25% with DCP, p < 0.001). In multivariate analysis, after adjusting for stage of diabetic retinopathy and DME, EZ disruption was only associated with nonperfusion in CC (p value = 0.03). According to the linear regression model, there was a statistically significant correlation between logMAR visual acuity and EZ disruption in the dry macular group (p = 0.041).

Conclusion

In patients with diabetic retinopathy, choriocapillaris nonperfusion may play a more significant role in photoreceptor loss than retinal nonperfusion.

目的：应用面光学相干断层扫描（OCT）和OCT血管造影（OCTA）评价糖尿病患者绒毛膜毛细血管（CC）、视网膜浅毛细血管丛（SCP）和深毛细血管丛（DCP）非灌注时椭球区（EZ）破坏的共定位。方法：采用RTVue XR Avanti仪器对41例糖尿病视网膜病变患者进行3 × 3 mm黄斑OCT和OCTA扫描。在校正阴影伪影后，使用高斯混合模型聚类方法对正面OCT板的EZ完整性进行评估，并与11名年龄匹配的正常患者的相应EZ正面OCT进行比较。类似的技术用于检测毛细管非灌注使用CC面OCTA。同时生成SCP和DCP的几何灌注密度（GPD）图。将CC、SCP和DCP的毛细血管非灌注图与EZ破坏产生的图逐像素进行比较。结果：本研究纳入21例糖尿病性黄斑水肿（DME）患者和20例无黄斑水肿的糖尿病性视网膜病变患者。两组糖尿病视网膜病变中，无灌注绒毛膜毛细血管损伤的重叠程度明显大于无灌注绒毛膜毛细血管损伤（干性黄斑组：CC为33.15%，SCP为0.46%，DCP为1.70%）。结论：在糖尿病视网膜病变患者中，绒毛膜毛细血管损伤在光受体丧失中的作用可能比无灌注视网膜损伤更显著。

{"title":"Colocalization of Ellipsoid Zone Disruption With Capillary Nonperfusion in Different Retinal Vascular Layers and Choriocapillaris on En Face OCT of Diabetic Patients","authors":"Reza Mirshahi, Amir Rahdar, Mohamad Javad Ahmadi, Kaveh Fadakar, Ali Torkashvand, Shahbaz Nekoozadeh, Khalil Ghasemi Falavarjani","doi":"10.1111/micc.70000","DOIUrl":"10.1111/micc.70000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>To assess the colocalization of ellipsoid zone (EZ) disruption with nonperfusion in choriocapillaris (CC), retinal superficial capillary plexus (SCP), and deep capillary plexus (DCP) in diabetic patients using en face optical coherence tomography (OCT) and OCT angiography (OCTA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Macular OCT and OCTA scans (3 × 3 mm) of 41 patients with diabetic retinopathy were obtained using an RTVue XR Avanti instrument. After correcting the shadow artifacts, EZ integrity was assessed in the en face OCT slab using the Gaussian mixture model clustering method compared with the corresponding EZ en face OCT of 11 age-matched normal patients. A similar technique was used for detecting capillary nonperfusion using CC en face OCTA. Geometric perfusion density (GPD) maps were also generated for the SCP and DCP. Maps of capillary nonperfusion in the CC, SCP, and DCP were compared pixel by pixel with the map generated from EZ disruption.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-one patients with diabetic macular edema (DME) and 20 patients with diabetic retinopathy without macular edema were included in this study. In both groups, the overlap of EZ disruption was significantly greater with choriocapillaris nonperfusion than with nonperfusion in the SCP and DCP (dry macular group: 33.15% with CC vs. 0.46% with SCP vs. 1.70% with DCP, <i>p</i> < 0.001; DME group: 29.81% with CC vs. 1.22% with SCP vs. 6.25% with DCP, <i>p</i> < 0.001). In multivariate analysis, after adjusting for stage of diabetic retinopathy and DME, EZ disruption was only associated with nonperfusion in CC (<i>p</i> value = 0.03). According to the linear regression model, there was a statistically significant correlation between logMAR visual acuity and EZ disruption in the dry macular group (<i>p</i> = 0.041).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In patients with diabetic retinopathy, choriocapillaris nonperfusion may play a more significant role in photoreceptor loss than retinal nonperfusion.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895970","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

Abstracts From the 49th Annual Meeting of Japanese Society for Microcirculation 日本微循环学会第 49 届年会摘要：2024 年 2 月 23-24 日，日本埼玉县声波市。

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2024-12-14 DOI: 10.1111/micc.12895

引用次数: 0

Models of Hydration Dependent Lymphatic Opening, Interstitial Fluid Flows and Ambipolar Diffusion 取决于水合作用的淋巴管开放、间质流和常压扩散模型。

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2024-11-21 DOI: 10.1111/micc.12894

Alf H. Øien, Olav Tenstad, Helge Wiig

Objective

A theoretical understanding of fluid exchange and the role of initial lymph formation in tissues through mathematical/physical modeling is lacking.

Methods

Here, we present three models for tissues rich in negative fixed charges due to glycosaminoglycans interacting with the extracellular matrix.

Results

We first model a lymphatic opening mechanism at relevant hydrations of the interstitium. At each hydration affecting tissue strain, two equations coupled in time are developed and solved with the new lymphatic opening and particle draining mechanism. The lymphatic opening mechanism is then included in a new model of interstitial fluid and macromolecular flow where the influence of different exclusion and available volumes for charged and neutral particles are quantified. For therapeutic interactions with cells, essential differences are found between electrically charged and neutral therapeutic substances. The interstitial fluid hydrostatic pressure gradient and flow are expressed through an extended Darcy equation, derived using similar methods as in kinetic theory of dense gases and fluid flows. Finally, a model for ambipolar diffusion of electrically charged macromolecules in tissue is developed.

Conclusions

Our study will inform transport of charged and neutral macromolecules between the vasculature, interstitium, and the lymphatic system, thus having implications for tissue uptake of therapeutic agents.

目的：目前还缺乏通过数学/物理建模对组织中液体交换和初始淋巴形成作用的理论认识：缺乏通过数学/物理建模对组织中液体交换和初始淋巴形成的作用的理论理解。方法：在此，我们提出了三种组织模型，这些组织因糖胺聚糖与细胞外基质相互作用而富含固定负电荷：我们首先模拟了间质相关水合作用下的淋巴开放机制。在每个影响组织应变的水合作用下，我们建立了两个时间耦合方程，并利用新的淋巴开放和微粒排出机制进行求解。然后将淋巴开放机制纳入间质流体和大分子流动的新模型中，对带电粒子和中性粒子的不同排斥和可用体积的影响进行量化。在治疗药物与细胞的相互作用方面，带电和中性治疗药物之间存在本质区别。间质流体的静水压力梯度和流动是通过扩展达西方程来表示的，其推导方法与稠密气体和流体流动的动力学理论类似。最后，建立了带电大分子在组织中的极性扩散模型：我们的研究将为带电和中性大分子在血管、间质和淋巴系统之间的传输提供信息，从而对治疗药物的组织吸收产生影响。

{"title":"Models of Hydration Dependent Lymphatic Opening, Interstitial Fluid Flows and Ambipolar Diffusion","authors":"Alf H. Øien, Olav Tenstad, Helge Wiig","doi":"10.1111/micc.12894","DOIUrl":"10.1111/micc.12894","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>A theoretical understanding of fluid exchange and the role of initial lymph formation in tissues through mathematical/physical modeling is lacking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we present three models for tissues rich in negative fixed charges due to glycosaminoglycans interacting with the extracellular matrix.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We first model a lymphatic opening mechanism at relevant hydrations of the interstitium. At each hydration affecting tissue strain, two equations coupled in time are developed and solved with the new lymphatic opening and particle draining mechanism. The lymphatic opening mechanism is then included in a new model of interstitial fluid and macromolecular flow where the influence of different exclusion and available volumes for charged and neutral particles are quantified. For therapeutic interactions with cells, essential differences are found between electrically charged and neutral therapeutic substances. The interstitial fluid hydrostatic pressure gradient and flow are expressed through an extended Darcy equation, derived using similar methods as in kinetic theory of dense gases and fluid flows. Finally, a model for ambipolar diffusion of electrically charged macromolecules in tissue is developed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study will inform transport of charged and neutral macromolecules between the vasculature, interstitium, and the lymphatic system, thus having implications for tissue uptake of therapeutic agents.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682275","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: 0