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Brain Microvascular Pericyte Pathology Linking Alzheimer's Disease to Diabetes 将阿尔茨海默病与糖尿病联系起来的脑微血管周皮病理学
IF 1.9 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-09-02 DOI: 10.1111/micc.12877
Kareem El-Ghazawi, Ukpong B. Eyo, Shayn M. Peirce

The brain microvasculature, which delivers oxygen and nutrients and forms a critical barrier protecting the central nervous system via capillaries, is deleteriously affected by both Alzheimer's disease (AD) and type 2 diabetes (T2D). T2D patients have an increased risk of developing AD, suggesting potentially related microvascular pathological mechanisms. Pericytes are an ideal cell type to study for functional links between AD and T2D. These specialized capillary-enwrapping cells regulate capillary density, lumen diameter, and blood flow. Pericytes also maintain endothelial tight junctions to ensure blood–brain barrier integrity, modulation of immune cell extravasation, and clearance of toxins. Changes in these phenomena have been observed in both AD and T2D, implicating “pericyte pathology” as a common feature of AD and T2D. This review examines the mechanisms of AD and T2D from the perspective of the brain microvasculature, highlighting how pericyte pathology contributes to both diseases. Our review identifies voids in understanding how AD and T2D negatively impact the brain microvasculature and suggests future studies to examine the intersections of these diseases.

大脑微血管通过毛细血管输送氧气和营养物质,并形成保护中枢神经系统的重要屏障,但阿尔茨海默病(AD)和 2 型糖尿病(T2D)都会对大脑微血管产生有害影响。2型糖尿病患者罹患阿尔茨海默病的风险增加,这表明微血管病理机制可能与此有关。周细胞是研究 AD 和 T2D 之间功能联系的理想细胞类型。这些特化的毛细血管包裹细胞可调节毛细血管密度、管腔直径和血流量。周细胞还维持内皮紧密连接,以确保血脑屏障的完整性、免疫细胞外渗的调节和毒素的清除。AD 和 T2D 均可观察到这些现象的变化,这表明 "周细胞病理学 "是 AD 和 T2D 的共同特征。本综述从脑部微血管的角度研究了注意力缺失症和终末期糖尿病的发病机制,强调了周细胞病理学是如何导致这两种疾病的。我们的综述指出了在理解注意力缺失症和终末期糖尿病如何对脑部微血管产生负面影响方面存在的不足,并提出了今后研究这些疾病的交叉点的建议。
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引用次数: 0
Imaging Hypoxia to Predict Primary Neuronal Cell Damage in Branch Retinal Artery Occlusion 通过缺氧成像预测视网膜分支动脉闭塞的原发性神经元细胞损伤
IF 1.9 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-08-30 DOI: 10.1111/micc.12883
Sara Z. Jamal, Blake W. Dieckmann, Gary W. McCollum, John S. Penn, Ashwath Jayagopal, MD Imam Uddin

Purpose

To develop a reliable method to generate a mouse model of branch retinal artery occlusion (BRAO) using laser-induced thrombosis of a major artery in the mouse retina. Also, to develop a reliable method to detect retinal hypoxia as predictive biomarker for the risk of neuronal cell damage in BRAO.

Methods

A reliable and reproducible model of laser-induced BRAO was developed in mouse retina using Rose Bengal. To characterize retinal hypoxia in BRAO, pimonidazole immunostaining and HYPOX-4 molecular imaging methods were used. Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) was used to characterize neuronal cell damage in the BRAO retina. Expression of mRNA in retinal tissues from BRAO and age-matched control retinas were analyzed using qRT-PCR.

Results

Occlusion of a branch retinal artery near the optic nerve head (ONH) caused a pattern of retinal tissue hypoxia covering about 12.5% of the entire retina. TUNEL-positive cells were localized in all layers in BRAO retinal tissue cross sections. In addition, qRT-PCR data analysis suggests that BRAO is associated with both inflammation and hypoxia.

Conclusions

This study provides a reliable method for BRAO in mouse retina and demonstrates the utility of molecular imaging method to detect retinal hypoxia as predictive biomarker for the risk of neuronal cell damage in BRAO. In addition, our data suggest that BRAO retinas are associated with inflammation and also associated with hypoxia-related neuronal cell damage.

Perspectives

Imaging areas of retinal hypoxia may provide accurate diagnosis, evaluating retinal tissue injury from BRAO.

目的:利用激光诱导的小鼠视网膜大动脉血栓形成,建立视网膜分支动脉闭塞(BRAO)小鼠模型的可靠方法。同时,开发一种检测视网膜缺氧的可靠方法,作为 BRAO 中神经细胞损伤风险的预测性生物标志物:方法:在小鼠视网膜上用玫瑰红染色法建立了一个可靠、可重复的激光诱导 BRAO 模型。为了描述 BRAO 中视网膜缺氧的特征,采用了波尼哒唑免疫染色法和 HYPOX-4 分子成像法。末端脱氧核苷酸转移酶 dUTP 缺口标记(TUNEL)用于描述 BRAO 视网膜神经细胞损伤的特征。使用 qRT-PCR 分析了 BRAO 视网膜组织和年龄匹配的对照视网膜组织中 mRNA 的表达:结果:视神经头(ONH)附近的视网膜分支动脉闭塞导致视网膜组织缺氧,缺氧面积约占整个视网膜的 12.5%。在 BRAO 视网膜组织横切面上,TUNEL 阳性细胞分布在所有视网膜层。此外,qRT-PCR 数据分析表明,BRAO 与炎症和缺氧有关:本研究提供了一种可靠的小鼠视网膜 BRAO 检测方法,并证明了分子成像方法在检测视网膜缺氧方面的实用性,可作为 BRAO 神经元细胞损伤风险的预测性生物标志物。此外,我们的数据还表明,BRAO 视网膜与炎症有关,也与缺氧相关的神经细胞损伤有关:视网膜缺氧区域成像可提供准确诊断,评估 BRAO 引起的视网膜组织损伤。
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引用次数: 0
Vascular Function and Ion Channels in Alzheimer's Disease 阿尔茨海默病的血管功能和离子通道
IF 1.9 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-08-27 DOI: 10.1111/micc.12881
Jade L. Taylor, Miguel Martin-Aragon Baudel, Madeline Nieves-Cintron, Manuel F. Navedo

This review paper explores the critical role of vascular ion channels in the regulation of cerebral artery function and examines the impact of Alzheimer's disease (AD) on these processes. Vascular ion channels are fundamental in controlling vascular tone, blood flow, and endothelial function in cerebral arteries. Dysfunction of these channels can lead to impaired cerebral autoregulation, contributing to cerebrovascular pathologies. AD, characterized by the accumulation of amyloid beta (Aβ) plaques and neurofibrillary tangles, has been increasingly linked to vascular abnormalities, including altered vascular ion channel activity. Here, we briefly review the role of vascular ion channels in cerebral blood flow control and neurovascular coupling. We then examine the vascular defects in AD, the current understanding of how AD pathology affects vascular ion channel function, and how these changes may lead to compromised cerebral blood flow and neurodegenerative processes. Finally, we provide future perspectives and conclusions. Understanding this topic is important as ion channels may be potential therapeutic targets for improving cerebrovascular health and mitigating AD progression.

这篇综述论文探讨了血管离子通道在调节脑动脉功能中的关键作用,并研究了阿尔茨海默病(AD)对这些过程的影响。血管离子通道是控制脑动脉血管张力、血流量和内皮功能的基础。这些通道的功能失调会导致大脑自动调节功能受损,从而引发脑血管病变。以淀粉样β(Aβ)斑块和神经纤维缠结的积累为特征的注意力缺失症与血管异常(包括血管离子通道活性的改变)的关系日益密切。在此,我们简要回顾了血管离子通道在脑血流控制和神经血管耦合中的作用。然后,我们研究了 AD 的血管缺陷、目前对 AD 病理如何影响血管离子通道功能的理解,以及这些变化如何可能导致脑血流受损和神经退行性过程。最后,我们提出了未来的展望和结论。了解这一主题非常重要,因为离子通道可能是改善脑血管健康和缓解 AD 进展的潜在治疗靶点。
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引用次数: 0
Different Measures of Hyperglycemia Are Negatively Associated With Skin Microvascular Flowmotion: The Maastricht Study 不同的高血糖测量值与皮肤微血管流动呈负相关:马斯特里赫特研究
IF 1.9 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-08-22 DOI: 10.1111/micc.12882
X. Zhao, C. Schalkwijk, A. Kroon, M. T. Schram, C. Stehouwer, A. Houben

Objective

Diabetes can lead to microvascular complications such as diabetic neuropathy, nephropathy, and retinopathy. Hyperglycemia may initiate microvascular function impairment early in the course of diabetes, even prior to its clinical establishment during the pre-diabetes stage. Microvascular vasomotion, that is, the rhythmic arteriolar constriction and dilation, is an important function that regulates oxygen and nutrient delivery within the tissue and regulates peripheral resistance. Using laser Doppler flowmetry (LDF), vasomotion in skin microcirculation can be measured as flowmotion. Changes in flowmotion have been shown in individuals with obesity, and type 1 or type 2 diabetes mellitus. However, no data are available on associations between hyperglycemia and flowmotion in the general population. Our aim was to study whether measures of hyperglycemia were associated with different components of skin microvascular flowmotion (SMF) in a population-based cohort (The Maastricht Study).

Methods

Data from 7293 participants of The Maastricht Study were used. SMF was measured using LDF. Endothelial, neurogenic and myogenic component SMF power were used as dependent variables. We investigated the associations of glucose metabolism status (normal glucose metabolism, prediabetes, and type 2 diabetes mellitus), measures of hyperglycemia (fasting plasma glucose [FPG], 2-h post-load glucose [2 h-PG], HbA1c, advanced glycation end-products [AGEs] assessed as skin autofluorescence [SAF]), and indices of glucose variability (incremental glucose peak [IGP] and continuous glucose monitoring [CGM] -assessed as standard deviation [SD]) with each component of SMF power. We used linear regression analyses with adjustments for confounders, and trend analyses.

Results

We observed consistent negative associations between HbA1c levels and all three (endothelial, neurogenic, and myogenic) skin microvascular flowmotion (SMF) powers in the additionally adjusted model. Similarly, in the conservative model, we found that multiple hyperglycemia metrics such as GMS trend, PreD, T2DM, FPG, 2 h-PG, and HbA1c were consistently negatively associated with all three SMF powers.

Conclusions

We showed that skin microvascular flowmotion is reduced in individuals with (pre)diabetes. In addition, different measures of hyperglycemia are negatively associated with skin microvascular flowmotion.

目的:糖尿病可导致微血管并发症,如糖尿病神经病变、肾病和视网膜病变。高血糖可能在糖尿病病程的早期,甚至在糖尿病前期临床症状出现之前,就已经开始损害微血管功能。微血管运动,即有节奏的动脉收缩和扩张,是调节组织内氧气和营养输送以及调节外周阻力的重要功能。利用激光多普勒血流测量仪(LDF),可将皮肤微循环中的血管运动测量为血流运动。肥胖症患者、1 型或 2 型糖尿病患者的血流运动都会发生变化。然而,目前还没有关于普通人群中高血糖与血流运动之间关系的数据。我们的目的是研究在一个基于人群的队列(马斯特里赫特研究)中,高血糖的测量值是否与皮肤微血管流动(SMF)的不同组成部分有关:方法:采用马斯特里赫特研究 7293 名参与者的数据。采用 LDF 测量 SMF。内皮、神经源和肌源性成分 SMF 功率被用作因变量。我们研究了葡萄糖代谢状态(正常葡萄糖代谢、糖尿病前期和 2 型糖尿病)、高血糖测量值(空腹血浆葡萄糖[FPG]、负荷后 2 小时血糖[2 h-PG]、HbA1c、高级糖化终产物[高级糖化终产物])与 SMF 的相关性、高级糖化终产物[AGEs],以皮肤自发荧光[SAF]评估),以及葡萄糖变异性指数(增量葡萄糖峰值[IGP]和连续葡萄糖监测[CGM],以标准差[SD]评估)与 SMF 功率的每个组成部分。我们采用了线性回归分析,并对混杂因素进行了调整,还进行了趋势分析:结果:在附加调整模型中,我们观察到 HbA1c 水平与所有三种(内皮、神经源和肌源性)皮肤微血管血流运动(SMF)功率之间存在一致的负相关。同样,在保守模型中,我们发现 GMS 趋势、PreD、T2DM、FPG、2 h-PG 和 HbA1c 等多个高血糖指标与所有三种 SMF 功率均呈负相关:我们的研究表明,糖尿病(前期)患者的皮肤微血管流动性降低。结论:我们的研究表明,糖尿病(前期)患者的皮肤微血管流动性降低,此外,不同的高血糖测量指标与皮肤微血管流动性呈负相关。
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引用次数: 0
Ninjin'yoeito Modulates Baseline and Reperfusion-Induced Changes in the Arteriole Diameter and Blood Flow in the Cerebral Cortex of Anesthetized Mice 宁神佑人调节麻醉小鼠大脑皮层动脉血管直径和血流量的基线变化和再灌注诱导的变化
IF 1.9 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-08-09 DOI: 10.1111/micc.12880
Nobuhiro Watanabe, Kaori Iimura, Harumi Hotta

Objective

Intragastric administration of ninjin'yoeito (NYT), a traditional Japanese herbal medicine, reportedly prevents the decrease in baseline cerebral blood flow (CBF) in the cortex following gastric administration of water. We investigated the effect of NYT on baseline and dynamic changes in cerebral cortical arteriole diameter.

Methods

Urethane-anesthetized mice were intragastrically administered 1 g/kg NYT or distilled water (DW). The artery in the left parietal cortex was imaged using two-photon microscopy. The baseline diameter of penetrating arterioles was measured before and 50–60 min after administration. Dynamic CBF and arteriole diameter changes before, during, and after transient occlusion of the left common carotid artery were measured approximately 10 min after administration.

Results

DW decreased the baseline diameter of the penetrating arterioles, whereas NYT did not. During occlusion, the increase in penetrating arteriole diameter was comparable for DW and NYT; however, during reperfusion, the return to preocclusion diameter was slower for NYT than DW. Laser-speckle contrast imaging confirmed that CBF, although comparable during occlusion, was higher during reperfusion for NYT than DW.

Conclusions

These results suggest that NYT attenuates vasoconstriction in penetrating arterioles after intragastric administration and during cerebral reperfusion, contributing to CBF regulation.

目的据报道,胃内注射日本传统草药 "忍者"(NYT)可防止胃内注射水后大脑皮层基线脑血流量(CBF)的减少。我们研究了NYT对大脑皮层动脉直径基线和动态变化的影响:方法:给尿烷麻醉的小鼠胃内注射 1 g/kg NYT 或蒸馏水(DW)。使用双光子显微镜对左顶叶皮层的动脉进行成像。在给药前和给药后 50-60 分钟测量穿透动脉血管的基线直径。给药后约 10 分钟,测量左侧颈总动脉瞬时闭塞前、闭塞过程中和闭塞后的动态 CBF 和动脉血管直径变化:结果:DW降低了穿透性动脉血管的基线直径,而NYT则没有。在闭塞过程中,DW 和 NYT 的穿通动脉直径增加速度相当;但在再灌注过程中,NYT 恢复到闭塞前直径的速度比 DW 慢。激光斑点对比成像证实,虽然闭塞期间的 CBF 不相上下,但再灌注期间 NYT 的 CBF 要高于 DW:这些结果表明,NYT可减轻胃内给药后和脑再灌注期间穿透性动脉血管的血管收缩,从而有助于调节CBF。
{"title":"Ninjin'yoeito Modulates Baseline and Reperfusion-Induced Changes in the Arteriole Diameter and Blood Flow in the Cerebral Cortex of Anesthetized Mice","authors":"Nobuhiro Watanabe,&nbsp;Kaori Iimura,&nbsp;Harumi Hotta","doi":"10.1111/micc.12880","DOIUrl":"10.1111/micc.12880","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Intragastric administration of ninjin'yoeito (NYT), a traditional Japanese herbal medicine, reportedly prevents the decrease in baseline cerebral blood flow (CBF) in the cortex following gastric administration of water. We investigated the effect of NYT on baseline and dynamic changes in cerebral cortical arteriole diameter.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Urethane-anesthetized mice were intragastrically administered 1 g/kg NYT or distilled water (DW). The artery in the left parietal cortex was imaged using two-photon microscopy. The baseline diameter of penetrating arterioles was measured before and 50–60 min after administration. Dynamic CBF and arteriole diameter changes before, during, and after transient occlusion of the left common carotid artery were measured approximately 10 min after administration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DW decreased the baseline diameter of the penetrating arterioles, whereas NYT did not. During occlusion, the increase in penetrating arteriole diameter was comparable for DW and NYT; however, during reperfusion, the return to preocclusion diameter was slower for NYT than DW. Laser-speckle contrast imaging confirmed that CBF, although comparable during occlusion, was higher during reperfusion for NYT than DW.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results suggest that NYT attenuates vasoconstriction in penetrating arterioles after intragastric administration and during cerebral reperfusion, contributing to CBF regulation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"31 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141909940","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
Retinal Vessel Functional Responses in South Africans Living With and Without HIV: The EndoAfrica-NWU Study 南非艾滋病病毒感染者和非艾滋病病毒感染者的视网膜血管功能反应:EndoAfrica-NWU 研究。
IF 1.9 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-08-06 DOI: 10.1111/micc.12878
Catharina Elizabeth Myburgh-Jacobsz, Shani Botha-Le Roux, Konstantin Kotliar, Annemarie Wentzel, Adriaan Jacobs, Patrick De Boever, Nandu Goswami, Hans Strijdom, Wayne Smith

Objectives

The effects of HIV and antiretroviral therapy (ART) on microvascular function are poorly explored. We compared retinal vessel functional responses to flicker light-induced provocation (FLIP) in people living with HIV (PLWH) and people living without HIV (PLWoutH).

Methods

We included 115 PLWH and 51 PLWoutH with a median age of 41 years. Treated PLWH received similar first-line fixed-dose combination ART. Clinical characteristics and retinal vessels functional responses to FLIP were compared in (a) PLWH and PLWoutH; and (b) PLWH groups stratified by the median of (i) CD4-count (511 cells/mm3), (ii) viral load (50 copies/mL), and (iii) ART duration (57.6 months).

Results

PLWH were older, smoked more, and had a lower prevalence of hypertension than PLWoutH (p < 0.05). Almost 64% of PLWH were infected for more than 5 years. Retinal vessel responses to FLIP were similar between PLWH and PLWoutH after taking confounders into account. In addition, PLWH subgroups stratified according to immuno-virological status by CD4-count, viral load, and ART duration showed no differences in retinal vessel responses to FLIP.

Conclusion

Living with HIV and receiving ART were not associated with altered microvascular function as assessed with dynamic retinal vessel analysis in a South African case–control study.

目的:艾滋病病毒和抗逆转录病毒疗法(ART)对微血管功能的影响尚未得到充分研究。我们比较了 HIV 感染者(PLWH)和非 HIV 感染者(PLWoutH)的视网膜血管对闪烁光诱导(FLIP)的功能反应:研究对象包括 115 名艾滋病病毒感染者和 51 名非艾滋病病毒感染者,中位年龄为 41 岁。接受治疗的 PLWH 接受类似的一线固定剂量联合抗逆转录病毒疗法。比较了(a) PLWH 和 PLWoutH;(b) 按(i) CD4 细胞数(511 cells/mm3)、(ii) 病毒载量(50 copies/mL)和(iii) ART 持续时间(57.6 个月)中位数分层的 PLWH 组的临床特征和对 FLIP 的视网膜血管功能反应:结果:与未感染艾滋病毒的 PLWH 相比,感染艾滋病毒的 PLWH 年龄更大、吸烟更多,高血压患病率更低(P在南非的一项病例对照研究中,通过动态视网膜血管分析评估发现,感染艾滋病毒和接受抗逆转录病毒疗法与微血管功能的改变无关。
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引用次数: 0
Lymphatic Capillarization in Different Fiber Types of Rat Skeletal Muscles With Growth and Age 大鼠骨骼肌不同纤维类型的淋巴毛细血管化与生长和年龄有关
IF 1.9 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-07-27 DOI: 10.1111/micc.12879
Yoshikazu Taketa, Keigo Tamakoshi, Kazuki Hotta, Shutaro Maki, Toru Taguchi, Hideaki Takahashi

Objective

To clarify the effect of growth and advancing age on lymphatic capillarization in rat skeletal muscles, we examined the histological and biochemical changes of lymphatic capillaries in different fiber types of skeletal muscles across juvenile, young, and middle-aged generations.

Methods

We collected the tibialis anterior (TA), extensor digitorum longus (EDL), and soleus (SOL) muscles. Immunohistochemical staining using LYVE-1 and CD31 markers was used for lymphatic and blood capillaries, respectively. Real-time PCR was used to analyze mRNA expression of lymphangiogenic factors.

Results

The density of LYVE-1-positive lymphatic capillaries in the muscles peaked during the juvenile period and subsequently decreased with increasing age. In contrast to blood capillaries, fast-twitch dominant muscles (i.e., TA and EDL) exhibited an age-related decrease in lymphatic capillaries. Similar to blood capillaries, lymphatic capillaries were abundant in SOL, a slow-twitch dominant muscle, which showed less susceptibility to age-related lymphatic decline. The mRNA expression of lymphangiogenic factors was significantly upregulated in SOL and decreased in all muscles of middle-aged rats.

Conclusions

The age-related decrease of lymphatic capillaries in fast-twitch muscles might be associated with age-related muscle atrophy.

方法 我们采集了大鼠胫骨前肌(TA)、趾长伸肌(EDL)和比目鱼肌(SOL)。分别使用 LYVE-1 和 CD31 标记对淋巴管和毛细血管进行免疫组化染色。结果肌肉中 LYVE-1 阳性淋巴毛细血管的密度在幼年期达到高峰,随后随着年龄的增长而下降。与血毛细血管不同,快肌优势肌肉(即 TA 和 EDL)的淋巴毛细血管随年龄增长而减少。与血毛细血管类似,淋巴毛细血管在 SOL 肌肉中也很丰富,SOL 肌肉是一种慢速运动优势肌肉,其淋巴衰退与年龄有关的敏感性较低。淋巴管生成因子的 mRNA 表达在 SOL 中显著上调,而在中年大鼠的所有肌肉中均有所下降。
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引用次数: 0
Ion Channels Remodeling in the Regulation of Vascular Hyporesponsiveness During Shock 离子通道重塑对休克期间血管低反应性的调节作用
IF 1.9 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-07-16 DOI: 10.1111/micc.12874
Keqing Li, Yuan Li, Yinghong Chen, Tangting Chen, Yan Yang, Pengyun Li

Shock is characterized with vascular hyporesponsiveness to vasoconstrictors, thereby to cause refractory hypotension, insufficient tissue perfusion, and multiple organ dysfunction. The vascular hyporeactivity persisted even though norepinephrine and fluid resuscitation were administrated, it is of critical importance to find new potential target. Ion channels are crucial in the regulation of cell membrane potential and affect vasoconstriction and vasodilation. It has been demonstrated that many types of ion channels including K+ channels, Ca2+ permeable channels, and Na+ channels exist in vascular smooth muscle cells and endothelial cells, contributing to the regulation of vascular homeostasis and vasomotor function. An increasing number of studies suggested that the structural and functional alterations of ion channels located in arteries contribute to vascular hyporesponsiveness during shock, but the underlying mechanisms remained to be fully clarified. Therefore, the expression and functional changes in ion channels in arteries associated with shock are reviewed, to pave the way for further exploring the potential of ion channel-targeted compounds in treating refractory hypotension in shock.

休克的特点是血管对血管收缩剂反应迟钝,从而导致难治性低血压、组织灌注不足和多器官功能障碍。因此,寻找新的潜在靶点至关重要。离子通道是调节细胞膜电位的关键,影响着血管收缩和扩张。研究表明,血管平滑肌细胞和内皮细胞中存在多种类型的离子通道,包括 K+ 通道、Ca2+ 通透性通道和 Na+ 通道,它们在调节血管稳态和血管运动功能方面做出了贡献。越来越多的研究表明,位于动脉中的离子通道的结构和功能改变导致了休克时血管的低反应性,但其潜在机制仍有待完全阐明。因此,本文综述了与休克有关的动脉中离子通道的表达和功能变化,为进一步探索离子通道靶向化合物治疗休克难治性低血压的潜力铺平了道路。
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引用次数: 0
Tumor-Derived Exosomes Promote Tumor Growth Through Modulating Microvascular Hemodynamics in a Human Ovarian Cancer Xenograft Model 肿瘤外泌体通过调节人卵巢癌异种移植模型中的微血管血流动力学促进肿瘤生长
IF 1.9 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-07-15 DOI: 10.1111/micc.12876
Qin Wang, Xiaoyan Zhang, Bingwei Li, Xueting Liu, Ailing Li, Hongwei Li, Xiaohua Shi, Jianqun Han

Objective

Abnormal tumor vascular network contributes to aberrant blood perfusion and reduced oxygenation in tumors, which lead to poor efficacy of chemotherapy and radiotherapy. We aimed to explore the effects of the tumor-derived exosomes (TDEs) and C188-9 (a small molecule inhibitor of signal transducer and activator of transcription 3, STAT3) on tumor microvascular hemodynamics and determine which blood flow oscillations for various frequency intervals are responsible for these changes.

Methods

Microvascular hemodynamics parameters were recorded using a PeriFlux 6000 EPOS system in tumor surface in a nude mouse subcutaneous xenograft model. Oscillations of laser Doppler flowmetry (LDF) signal were investigated by wavelet transform analysis.

Results

TDEs facilitated tumor growth at least partially was associated with increasing blood flow in smaller vessels with lower speed and decreasing the blood flow at larger vessels with higher speed. Lower oxyhemoglobin saturation (SO2) on tumor surface was aggravated by TDEs, and C188-9 treatment significantly alleviated this decrease. Wavelet transform spectral analysis revealed that TDEs increased the amplitude of oscillations in four frequency intervals related to endothelial (NO-dependent and -independent), myogenic and neurogenic activities, and C188-9 had no effect on this increase.

Conclusions

TDEs facilitated tumor growth partially was associated with increasing blood flow in distributing vessels, reducing blood perfusion in larger vessels, and lowering SO2 on tumor surface. Enhanced vascular smooth muscle, endothelial and neurogenic activities occurred in tumor superficial zone.

目的:肿瘤血管网络异常会导致肿瘤血液灌注异常和氧含量降低,从而导致化疗和放疗疗效不佳。我们旨在探索肿瘤外泌体(TDEs)和 C188-9(一种信号转导子和转录激活子 3 STAT3 的小分子抑制剂)对肿瘤微血管血流动力学的影响,并确定不同频率间隔的血流振荡是造成这些变化的原因:方法:使用 PeriFlux 6000 EPOS 系统记录裸鼠皮下异种移植模型肿瘤表面的微血管血流动力学参数。通过小波变换分析研究了激光多普勒血流测量仪(LDF)信号的振荡:结果:TDEs 至少在一定程度上促进了肿瘤的生长,这与流速较低的小血管血流增加和流速较高的大血管血流减少有关。TDEs 加剧了肿瘤表面氧合血红蛋白饱和度(SO2)的降低,而 C188-9 治疗显著缓解了这种降低。小波变换频谱分析表明,TDEs 增加了与内皮(NO 依赖性和非依赖性)、肌源和神经源活动有关的四个频率区间的振荡幅度,而 C188-9 对这种增加没有影响:TDEs促进肿瘤生长的部分原因与增加分布血管的血流量、减少较大血管的血液灌注和降低肿瘤表面的二氧化硫有关。肿瘤浅表区的血管平滑肌、内皮细胞和神经原活动增强。
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引用次数: 0
Hemodynamic Characteristics of a Tortuous Microvessel Using High-Fidelity Red Blood Cell Resolved Simulations 利用高保真红细胞分辨模拟分析曲折微血管的血流动力学特征。
IF 1.9 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-07-11 DOI: 10.1111/micc.12875
Mir Md Nasim Hossain, Nien-Wen Hu, Ali Kazempour, Walter L. Murfee, Peter Balogh

Objective

Tortuous microvessels are characteristic of microvascular remodeling associated with numerous physiological and pathological scenarios. Three-dimensional (3D) hemodynamics in tortuous microvessels influenced by red blood cells (RBCs), however, are largely unknown, and important questions remain. Is blood viscosity influenced by vessel tortuosity? How do RBC dynamics affect wall shear stress (WSS) patterns and the near-wall cell-free layer (CFL) over a range of conditions? The objective of this work was to parameterize hemodynamic characteristics unique to a tortuous microvessel.

Methods

RBC-resolved simulations were performed using an immersed boundary method-based 3D fluid dynamics solver. A representative tortuous microvessel was selected from a stimulated angiogenic network obtained from imaging of the rat mesentery and digitally reconstructed for the simulations. The representative microvessel was a venule with a diameter of approximately 20 μm. The model assumes a constant diameter along the vessel length and does not consider variations due to endothelial cell shapes or the endothelial surface layer.

Results

Microvessel tortuosity was observed to increase blood apparent viscosity compared to a straight tube by up to 26%. WSS spatial variations in high curvature regions reached 23.6 dyne/cm2 over the vessel cross-section. The magnitudes of WSS and CFL thickness variations due to tortuosity were strongly influenced by shear rate and negligibly influenced by tube hematocrit levels.

Conclusions

New findings from this work reveal unique tortuosity-dependent hemodynamic characteristics over a range of conditions. The results provide new thought-provoking information to better understand the contribution of tortuous vessels in physiological and pathological processes and help improve reduced-order models.

目的:迂曲微血管是与多种生理和病理情况相关的微血管重塑的特征。然而,受红细胞(RBC)影响的迂曲微血管中的三维(3D)血液动力学在很大程度上是未知的,而且仍然存在一些重要问题。血液粘度是否受血管迂曲度的影响?在一系列条件下,红细胞动力学如何影响管壁剪切应力(WSS)模式和近壁无细胞层(CFL)?这项工作的目的是对迂曲微血管特有的血液动力学特征进行参数化:方法:使用基于沉浸边界法的三维流体动力学求解器进行了红细胞分辨模拟。从大鼠肠系膜成像获得的受刺激血管生成网络中选取了一条具有代表性的迂曲微血管,并对其进行了数字重建以进行模拟。代表性微血管是直径约为 20 μm 的静脉。该模型假定沿血管长度方向的直径不变,不考虑内皮细胞形状或内皮表层的变化:结果:与直管相比,观察到微血管迂曲会增加血液表观粘度达 26%。高曲率区域的 WSS 空间变化在血管横截面上达到 23.6 达因/平方厘米。迂曲导致的 WSS 和 CFL 厚度变化幅度受剪切率的影响很大,而试管血细胞比容水平的影响可以忽略不计:结论:这项研究的新发现揭示了在一系列条件下迂曲度依赖性血液动力学特征。这些结果为更好地理解迂曲血管在生理和病理过程中的作用提供了新的发人深省的信息,并有助于改进降阶模型。
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Microcirculation
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