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Blood flow regulates acvrl1 transcription via ligand-dependent Alk1 activity 血流通过配体依赖性 Alk1 活性调节 acvrl1 的转录。
IF 9.2 1区 医学 Q1 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-05-10 DOI: 10.1007/s10456-024-09924-w
Anthony R. Anzell, Amy B. Kunz, James P. Donovan, Thanhlong G. Tran, Xinyan Lu, Sarah Young, Beth L. Roman

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by the development of arteriovenous malformations (AVMs) that can result in significant morbidity and mortality. HHT is caused primarily by mutations in bone morphogenetic protein receptors ACVRL1/ALK1, a signaling receptor, or endoglin (ENG), an accessory receptor. Because overexpression of Acvrl1 prevents AVM development in both Acvrl1 and Eng null mice, enhancing ACVRL1 expression may be a promising approach to development of targeted therapies for HHT. Therefore, we sought to understand the molecular mechanism of ACVRL1 regulation. We previously demonstrated in zebrafish embryos that acvrl1 is predominantly expressed in arterial endothelial cells and that expression requires blood flow. Here, we document that flow dependence exhibits regional heterogeneity and that acvrl1 expression is rapidly restored after reinitiation of flow. Furthermore, we find that acvrl1 expression is significantly decreased in mutants that lack the circulating Alk1 ligand, Bmp10, and that, in the absence of flow, intravascular injection of BMP10 or the related ligand, BMP9, restores acvrl1 expression in an Alk1-dependent manner. Using a transgenic acvrl1:egfp reporter line, we find that flow and Bmp10 regulate acvrl1 at the level of transcription. Finally, we observe similar ALK1 ligand-dependent increases in ACVRL1 in human endothelial cells subjected to shear stress. These data suggest that ligand-dependent Alk1 activity acts downstream of blood flow to maintain or enhance acvrl1 expression via a positive feedback mechanism, and that ALK1 activating therapeutics may have dual functionality by increasing both ALK1 signaling flux and ACVRL1 expression.

遗传性出血性毛细血管扩张症(HHT)是一种常染色体显性遗传病,其特征是发生动静脉畸形(AVM),可导致严重的发病率和死亡率。HHT 主要是由骨形态发生蛋白受体 ACVRL1/ALK1 (一种信号受体)或内胚层蛋白受体 (ENG) (一种辅助受体)突变引起的。由于过表达 Acvrl1 可防止 Acvrl1 和 Eng 空位小鼠的 AVM 发生,因此增强 ACVRL1 的表达可能是开发 HHT 靶向疗法的一种有前途的方法。因此,我们试图了解 ACVRL1 的分子调控机制。我们之前在斑马鱼胚胎中证实,acvrl1 主要在动脉内皮细胞中表达,而且其表达需要血流的支持。在这里,我们发现血流依赖性表现出区域异质性,并且在恢复血流后,acvrl1 的表达会迅速恢复。此外,我们还发现,在缺乏循环 Alk1 配体 Bmp10 的突变体中,acvrl1 的表达明显降低,而在无血流的情况下,血管内注射 BMP10 或相关配体 BMP9 能以 Alk1 依赖性的方式恢复 acvrl1 的表达。利用转基因 acvrl1:egfp 报告基因系,我们发现血流和 Bmp10 在转录水平上调控 acvrl1。最后,我们在受剪切应力作用的人类内皮细胞中观察到类似的 ALK1 配体依赖性 ACVRL1 的增加。这些数据表明,配体依赖性 Alk1 活性在血流下游发挥作用,通过正反馈机制维持或增强 acvrl1 的表达,而 ALK1 激活疗法可能同时增加 ALK1 信号通量和 ACVRL1 的表达,从而具有双重功能。
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引用次数: 0
IC100, a humanized therapeutic monoclonal anti-ASC antibody alleviates oxygen-induced retinopathy in mice IC100是一种人源化治疗性单克隆抗ASC抗体,可减轻氧气诱导的小鼠视网膜病变。
IF 9.2 1区 医学 Q1 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-05-06 DOI: 10.1007/s10456-024-09917-9
Huijun Yuan, Shaoyi Chen, Matthew R. Duncan, Juan Pablo de Rivero Vaccari, Robert W. Keane, W. Dalton Dietrich, Tsung-Han Chou, Merline Benny, Augusto F. Schmidt, Karen Young, Kevin K. Park, Vittorio Porciatti, M. Elizabeth Hartnett, Shu Wu
<div><h3>Background</h3><p>Retinopathy of prematurity (ROP), which often presents with bronchopulmonary dysplasia (BPD), is among the most common morbidities affecting extremely premature infants and is a leading cause of severe vision impairment in children worldwide. Activations of the inflammasome cascade and microglia have been implicated in playing a role in the development of both ROP and BPD. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is pivotal in inflammasome assembly. Utilizing mouse models of both oxygen-induced retinopathy (OIR) and BPD, this study was designed to test the hypothesis that hyperoxia induces ASC speck formation, which leads to microglial activation and retinopathy, and that inhibition of ASC speck formation by a humanized monoclonal antibody, IC100, directed against ASC, will ameliorate microglial activation and abnormal retinal vascular formation.</p><h3>Methods</h3><p>We first tested ASC speck formation in the retina of ASC-citrine reporter mice expressing ASC fusion protein with a C-terminal citrine (fluorescent GFP isoform) using a BPD model that causes both lung and eye injury by exposing newborn mice to room air (RA) or 85% O<sub>2</sub> from postnatal day (P) 1 to P14. The retinas were dissected on P14 and retinal flat mounts were used to detect vascular endothelium with AF-594-conjugated isolectin B4 (IB4) and citrine-tagged ASC specks. To assess the effects of IC100 on an OIR model, newborn ASC citrine reporter mice and wildtype mice (C57BL/6 J) were exposed to RA from P1 to P6, then 75% O<sub>2</sub> from P7 to P11, and then to RA from P12 to P18. At P12 mice were randomized to the following groups: RA with placebo PBS (RA-PBS), O<sub>2</sub> with PBS (O<sub>2</sub>-PBS), O<sub>2</sub> + IC100 intravitreal injection (O<sub>2</sub>-IC100-IVT), and O<sub>2</sub> + IC100 intraperitoneal injection (O<sub>2</sub>-IC100-IP). Retinal vascularization was evaluated by flat mount staining with IB4. Microglial activation was detected by immunofluorescence staining for allograft inflammatory factor 1 (AIF-1) and CD206. Retinal structure was analyzed on H&E-stained sections, and function was analyzed by pattern electroretinography (PERG). RNA-sequencing (RNA-seq) of the retinas was performed to determine the transcriptional effects of IC100 treatment in OIR.</p><h3>Results</h3><p>ASC specks were significantly increased in the retinas by hyperoxia exposure and colocalized with the abnormal vasculature in both BPD and OIR models, and this was associated with increased microglial activation. Treatment with IC100-IVT or IC100-IP significantly reduced vaso-obliteration and intravitreal neovascularization. IC100-IVT treatment also reduced retinal microglial activation, restored retinal structure, and improved retinal function. RNA-seq showed that IC100 treatment corrected the induction of genes associated with angiogenesis, leukocyte migration, and VEGF signaling caused by O<sub>2</
背景:早产儿视网膜病变(ROP)通常伴有支气管肺发育不良(BPD),是影响极早产儿的最常见疾病之一,也是全球儿童视力严重受损的主要原因。炎性体级联和小胶质细胞的活化已被认为在 ROP 和 BPD 的发病过程中扮演了重要角色。含有卡巴酶招募结构域(ASC)的凋亡相关斑点样蛋白在炎症小体的组装中起着关键作用。本研究利用氧诱导视网膜病变(OIR)和BPD小鼠模型,旨在验证以下假设:高氧诱导ASC斑点形成,从而导致小胶质细胞活化和视网膜病变;通过针对ASC的人源化单克隆抗体IC100抑制ASC斑点形成,可改善小胶质细胞活化和视网膜血管异常形成:我们首先使用一种 BPD 模型检测了表达 ASC 与 C 端黄素(荧光 GFP 同工型)融合蛋白的 ASC-黄素报告小鼠视网膜中 ASC斑点的形成情况,该模型通过将新生小鼠从出生后第 1 天到第 14 天置于室内空气(RA)或 85%O2 中,导致肺部和眼部损伤。在 P14 日解剖视网膜,用 AF-594 结合物异选择素 B4 (IB4) 和黄铜标记的 ASC斑点检测视网膜平片的血管内皮。为了评估 IC100 对 OIR 模型的影响,新生 ASC 黄素报告小鼠和野生型小鼠(C57BL/6 J)从 P1 到 P6 暴露于 RA,然后从 P7 到 P11 暴露于 75% O2,再从 P12 到 P18 暴露于 RA。在 P12 小鼠被随机分为以下几组:RA 组与安慰剂 PBS 组(RA-PBS)、O2 组与 PBS 组(O2-PBS)、O2 + IC100 玻璃体内注射组(O2-IC100-IVT)和 O2 + IC100 腹腔注射组(O2-IC100-IP)。视网膜血管通过 IB4 平片染色进行评估。通过免疫荧光染色异体移植物炎症因子1(AIF-1)和CD206检测小胶质细胞的活化。H&E染色切片分析视网膜结构,模式视网膜电图(PERG)分析视网膜功能。对视网膜进行了 RNA 序列分析(RNA-seq),以确定 IC100 治疗对 OIR 的转录影响:结果:在BPD和OIR模型中,视网膜中的ASC斑点因高氧暴露而明显增加,并与异常血管共定位,这与小胶质细胞活化增加有关。使用 IC100-IVT 或 IC100-IP 治疗可显著减少血管淤血和玻璃体内新生血管。IC100-IVT 治疗还降低了视网膜小胶质细胞的活化,恢复了视网膜结构,改善了视网膜功能。RNA-seq显示,IC100治疗纠正了氧气对血管生成、白细胞迁移和血管内皮生长因子信号转导相关基因的诱导。IC100 还纠正了 O2 对细胞连接组装、神经元投射和神经元识别相关基因的抑制作用:这些数据证明了 ASC 在 OIR 发病机制中的关键作用,以及人源化治疗性抗 ASC 抗体在治疗 OIR 小鼠中的疗效。因此,这种抗 ASC 抗体有可能被用于治疗与氧应激和视网膜病变相关的疾病,如 ROP。
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引用次数: 0
Somatic BrafV600E mutation in the cerebral endothelium induces brain arteriovenous malformations 脑内皮中的体细胞BrafV600E突变会诱发脑动静脉畸形。
IF 9.2 1区 医学 Q1 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-05-03 DOI: 10.1007/s10456-024-09918-8
Tianqi Tu, Jiaxing Yu, Chendan Jiang, Shikun Zhang, Jingwei Li, Jian Ren, Shiju Zhang, Yuan Zhou, Ziwei Cui, Haohan Lu, Xiaosheng Meng, Zhanjing Wang, Dong Xing, Hongqi Zhang, Tao Hong

Current treatments of brain arteriovenous malformation (BAVM) are associated with considerable risks and at times incomplete efficacy. Therefore, a clinically consistent animal model of BAVM is urgently needed to investigate its underlying biological mechanisms and develop innovative treatment strategies. Notably, existing mouse models have limited utility due to heterogenous and untypical phenotypes of AVM lesions. Here we developed a novel mouse model of sporadic BAVM that is consistent with clinical manifestations in humans. Mice with BrafV600E mutations in brain ECs developed BAVM closely resembled that of human lesions. This strategy successfully induced BAVMs in mice across different age groups and within various brain regions. Pathological features of BAVM were primarily dilated blood vessels with reduced vascular wall stability, accompanied by spontaneous hemorrhage and neuroinflammation. Single-cell sequencing revealed differentially expressed genes that were related to the cytoskeleton, cell motility, and intercellular junctions. Early administration of Dabrafenib was found to be effective in slowing the progression of BAVMs; however, its efficacy in treating established BAVM lesions remained uncertain. Taken together, our proposed approach successfully induced BAVM that closely resembled human BAVM lesions in mice, rendering the model suitable for investigating the pathogenesis of BAVM and assessing potential therapeutic strategies.

目前治疗脑动静脉畸形(BAVM)的方法存在相当大的风险,有时疗效不佳。因此,迫切需要一种与临床一致的脑动静脉畸形动物模型来研究其潜在的生物学机制并开发创新的治疗策略。值得注意的是,现有的小鼠模型由于 AVM 病变的异质性和非典型表型而实用性有限。在这里,我们建立了一种与人类临床表现一致的散发性脑动静脉畸形的新型小鼠模型。脑EC发生BrafV600E突变的小鼠发生的BAVM与人类病变非常相似。这种策略成功地诱导了不同年龄组和不同脑区的小鼠发生脑血管瘤。BAVM的病理特征主要是血管扩张,血管壁稳定性降低,伴有自发性出血和神经炎症。单细胞测序发现了与细胞骨架、细胞运动和细胞间连接有关的差异表达基因。研究发现,早期服用达拉非尼能有效延缓脑动静脉畸形的进展;然而,它对治疗已形成的脑动静脉畸形病灶的疗效仍不确定。总之,我们提出的方法成功地诱导出了与人类小鼠BAVM病变非常相似的BAVM,使该模型适用于研究BAVM的发病机制和评估潜在的治疗策略。
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引用次数: 0
Correction: Granzyme B degrades extracellular matrix and promotes inflammation and choroidal neovascularization 更正:Granzyme B 能降解细胞外基质,促进炎症和脉络膜新生血管形成。
IF 9.2 1区 医学 Q1 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-05-03 DOI: 10.1007/s10456-024-09919-7
Gideon Obasanmi, Manjosh Uppal, Jing Z. Cui, Jeanne Xi, Myeong Jin Ju, Jun Song, Eleanor To, Siqi Li, Wania Khan, Darian Cheng, John Zhu, Lyden Irani, Isa Samad, Julie Zhu, Hyung-Suk Yoo, Alexandre Aubert, Jonathan Stoddard, Martha Neuringer, David J. Granville, Joanne A. Matsubara
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引用次数: 0
Systemic glucocorticoids use in post-COVID-syndrome patients does not affect retinal microcirculation COVID综合征后患者全身使用糖皮质激素不会影响视网膜微循环。
IF 9.2 1区 医学 Q1 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-05-03 DOI: 10.1007/s10456-024-09926-8
T. Kuchler, C. Schmaderer
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引用次数: 0
Systemic glucocorticoids link to long-term microvascular injury in COVID-19 全身糖皮质激素与 COVID-19 的长期微血管损伤有关。
IF 9.2 1区 医学 Q1 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-04-24 DOI: 10.1007/s10456-024-09923-x
Qian Yang, Cai Yun Xia, Ying Cai, Yan Fang Zhang, Dao Ting Li, Shu Qi Wu, Peng Hu
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引用次数: 0
Interleukin-6 drives endothelial glycocalyx damage in COVID-19 and bacterial sepsis 白细胞介素-6 在 COVID-19 和细菌性败血症中驱动内皮糖萼损伤
IF 9.2 1区 医学 Q1 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-04-10 DOI: 10.1007/s10456-024-09916-w
Carolin Christina Drost, Alexandros Rovas, Irina Osiaevi, Klaus Schughart, Alexander Lukasz, Wolfgang A. Linke, Hermann Pavenstädt, Philipp Kümpers

Damage of the endothelial glycocalyx (eGC) plays a central role in the development of vascular hyperpermeability and organ damage during systemic inflammation. However, the specific signalling pathways for eGC damage remain poorly defined. Aim of this study was to combine sublingual video-microscopy, plasma proteomics and live cell imaging to uncover further pathways of eGC damage in patients with coronavirus disease 2019 (COVID-19) or bacterial sepsis. This secondary analysis of the prospective multicenter MICROCODE study included 22 patients with COVID-19 and 43 patients with bacterial sepsis admitted to intermediate or intensive care units and 10 healthy controls. Interleukin-6 (IL-6) was strongly associated with damaged eGC and correlated both with eGC dimensions (rs=0.36, p = 0.0015) and circulating eGC biomarkers. In vitro, IL-6 reduced eGC height and coverage, which was inhibited by blocking IL-6 signalling with the anti-IL-6 receptor antibody tocilizumab or the Janus kinase inhibitor tofacitinib. Exposure of endothelial cells to 5% serum from COVID-19 or sepsis patients resulted in a significant decrease in eGC height, which was attenuated by co-incubation with tocilizumab. In an external COVID-19 cohort of 219 patients from Massachusetts General Hospital, a previously identified proteomic eGC signature correlated with IL-6 (rs=-0.58, p < 0.0001) and predicted the combined endpoint of 28-day mortality and/or intubation (ROC-AUC: 0.86 [95% CI: 0.81–0.91], p < 0.001). The data suggest that IL-6 may significantly drive eGC damage in COVID-19 and bacterial sepsis. Our findings provide valuable insights into pathomechanisms of vascular dysfunction during systemic inflammation and highlight the need for further in vivo studies.

内皮糖萼(eGC)的损伤在全身炎症期间血管高渗透性和器官损伤的发展中起着核心作用。然而,eGC损伤的具体信号通路仍未明确。本研究旨在结合舌下视频显微镜、血浆蛋白质组学和活细胞成像技术,进一步揭示2019年冠状病毒病(COVID-19)或细菌性败血症患者的eGC损伤途径。这项前瞻性多中心MICROCODE研究的二次分析包括22名COVID-19患者、43名入住中级或重症监护病房的细菌性败血症患者以及10名健康对照组。白细胞介素-6(IL-6)与受损的eGC密切相关,并与eGC尺寸(rs=0.36,p=0.0015)和循环中的eGC生物标志物相关。在体外,IL-6会降低eGC的高度和覆盖率,而用抗IL-6受体抗体托西珠单抗或Janus激酶抑制剂托法替尼阻断IL-6信号可抑制这种降低。将内皮细胞暴露于来自COVID-19或脓毒症患者的5%血清中会导致eGC高度显著下降,而与托珠单抗共孵育可减轻这种下降。在麻省总医院 219 名患者组成的 COVID-19 外部队列中,先前确定的蛋白质组 eGC 特征与 IL-6 相关(rs=-0.58,p <0.0001),并可预测 28 天死亡率和/或插管的综合终点(ROC-AUC:0.86 [95% CI:0.81-0.91],p <0.001)。这些数据表明,在 COVID-19 和细菌性败血症中,IL-6 可能会显著驱动 eGC 损伤。我们的研究结果为了解全身性炎症期间血管功能障碍的病理机制提供了有价值的见解,并强调了进一步开展体内研究的必要性。
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引用次数: 0
Navigating tumor angiogenesis: therapeutic perspectives and myeloid cell regulation mechanism 肿瘤血管生成导航:治疗视角与髓细胞调控机制
IF 9.2 1区 医学 Q1 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-04-06 DOI: 10.1007/s10456-024-09913-z
Fan Yang, Gloria Lee, Yi Fan

Sustained angiogenesis stands as a hallmark of cancer. The intricate vascular tumor microenvironment fuels cancer progression and metastasis, fosters therapy resistance, and facilitates immune evasion. Therapeutic strategies targeting tumor vasculature have emerged as transformative for cancer treatment, encompassing anti-angiogenesis, vessel normalization, and endothelial reprogramming. Growing evidence suggests the dynamic regulation of tumor angiogenesis by infiltrating myeloid cells, such as macrophages, myeloid-derived suppressor cells (MDSCs), and neutrophils. Understanding these regulatory mechanisms is pivotal in paving the way for successful vasculature-targeted cancer treatments. Therapeutic interventions aimed to disrupt myeloid cell-mediated tumor angiogenesis may reshape tumor microenvironment and overcome tumor resistance to radio/chemotherapy and immunotherapy.

持续的血管生成是癌症的标志。错综复杂的肿瘤血管微环境助长了癌症的发展和转移,增强了抗药性,并有助于免疫逃避。针对肿瘤血管的治疗策略已成为癌症治疗的变革,包括抗血管生成、血管正常化和内皮重编程。越来越多的证据表明,巨噬细胞、髓源抑制细胞(MDSCs)和中性粒细胞等浸润性髓系细胞对肿瘤血管生成具有动态调控作用。了解这些调控机制对于成功开展以血管为靶点的癌症治疗至关重要。旨在破坏髓系细胞介导的肿瘤血管生成的治疗干预措施可重塑肿瘤微环境,克服肿瘤对放射/化疗和免疫疗法的耐药性。
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引用次数: 0
The role of vasculature and angiogenesis in respiratory diseases 血管和血管生成在呼吸系统疾病中的作用
IF 9.2 1区 医学 Q1 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-04-05 DOI: 10.1007/s10456-024-09910-2
Maximilian Ackermann, Christopher Werlein, Edith Plucinski, Sophie Leypold, Mark P. Kühnel, Stijn E. Verleden, Hassan A. Khalil, Florian Länger, Tobias Welte, Steven J. Mentzer, Danny D. Jonigk

In European countries, nearly 10% of all hospital admissions are related to respiratory diseases, mainly chronic life-threatening diseases such as COPD, pulmonary hypertension, IPF or lung cancer. The contribution of blood vessels and angiogenesis to lung regeneration, remodeling and disease progression has been increasingly appreciated. The vascular supply of the lung shows the peculiarity of dual perfusion of the pulmonary circulation (vasa publica), which maintains a functional blood-gas barrier, and the bronchial circulation (vasa privata), which reveals a profiled capacity for angiogenesis (namely intussusceptive and sprouting angiogenesis) and alveolar-vascular remodeling by the recruitment of endothelial precursor cells. The aim of this review is to outline the importance of vascular remodeling and angiogenesis in a variety of non-neoplastic and neoplastic acute and chronic respiratory diseases such as lung infection, COPD, lung fibrosis, pulmonary hypertension and lung cancer.

在欧洲国家,近 10%的住院病人与呼吸系统疾病有关,主要是慢性阻塞性肺病、肺动脉高压、IPF 或肺癌等危及生命的慢性疾病。血管和血管生成对肺再生、重塑和疾病进展的贡献日益受到重视。肺部血管供应具有双重灌注的特点,即肺循环(公共血管)和支气管循环(私人血管),前者维持着功能性血气屏障,后者则通过招募内皮前体细胞,显示出血管生成(即肠内血管生成和发芽血管生成)和肺泡血管重塑的能力。本综述旨在概述血管重塑和血管生成在各种非肿瘤性和肿瘤性急慢性呼吸系统疾病(如肺部感染、慢性阻塞性肺病、肺纤维化、肺动脉高压和肺癌)中的重要性。
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引用次数: 0
Microglia in retinal angiogenesis and diabetic retinopathy 视网膜血管生成和糖尿病视网膜病变中的小胶质细胞。
IF 9.2 1区 医学 Q1 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-04-02 DOI: 10.1007/s10456-024-09911-1
Aiyan Hu, Mirko H. H. Schmidt, Nora Heinig

Diabetic retinopathy has a high probability of causing visual impairment or blindness throughout the disease progression and is characterized by the growth of new blood vessels in the retina at an advanced, proliferative stage. Microglia are a resident immune population in the central nervous system, known to play a crucial role in regulating retinal angiogenesis in both physiological and pathological conditions, including diabetic retinopathy. Physiologically, they are located close to blood vessels and are essential for forming new blood vessels (neovascularization). In diabetic retinopathy, microglia become widely activated, showing a distinct polarization phenotype that leads to their accumulation around neovascular tufts. These activated microglia induce pathogenic angiogenesis through the secretion of various angiogenic factors and by regulating the status of endothelial cells. Interestingly, some subtypes of microglia simultaneously promote the regression of neovascularization tufts and normal angiogenesis in neovascularization lesions. Modulating the state of microglial activation to ameliorate neovascularization thus appears as a promising potential therapeutic approach for managing diabetic retinopathy.

Graphical abstract

糖尿病视网膜病变极有可能在整个病程中导致视力损伤或失明,其特点是视网膜上的新血管在晚期增生。小胶质细胞是中枢神经系统中的常住免疫群体,已知在生理和病理条件下(包括糖尿病视网膜病变)在调节视网膜血管生成方面发挥着至关重要的作用。在生理学上,它们位于血管附近,对形成新血管(新生血管)至关重要。在糖尿病视网膜病变中,小胶质细胞被广泛激活,显示出独特的极化表型,导致它们聚集在新生血管丛周围。这些活化的小胶质细胞通过分泌各种血管生成因子和调节内皮细胞的状态,诱导致病性血管生成。有趣的是,某些亚型的小胶质细胞能同时促进新生血管丛的消退和新生血管病变中的正常血管生成。因此,调节小胶质细胞的活化状态以改善新生血管的形成似乎是治疗糖尿病视网膜病变的一种很有前景的潜在治疗方法。
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引用次数: 0
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Angiogenesis
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