Angiogenesis最新文献_第3页

Isolated human adipose microvessels retain native microvessel structure and recapitulate sprouting angiogenesis 分离的人体脂肪微血管保留了原有的微血管结构，并重现了新生血管

IF 9.2 1区医学

Angiogenesis Pub Date : 2025-03-06 DOI: 10.1007/s10456-025-09972-w

Sarah M. Moss, Thomas Gerton, Hannah A. Strobel, James B. Hoying

{"title":"Isolated human adipose microvessels retain native microvessel structure and recapitulate sprouting angiogenesis","authors":"Sarah M. Moss, Thomas Gerton, Hannah A. Strobel, James B. Hoying","doi":"10.1007/s10456-025-09972-w","DOIUrl":"10.1007/s10456-025-09972-w","url":null,"abstract":"<div><p>With interest growing in modeling more complex aspects of human disease in the laboratory, the need for effectively vascularizing human tissue models is becoming paramount. However, fully recreating human tissue microvasculatures is challenging given the multicellular complexity of the microvessel and microvessel-tissue interplay. Importantly, effective models should capture the dynamic activity of the perivascular cells of the perivascular niche, which are critical to tissue hemostasis and function. Isolated microvessel fragments from rodent adipose have been extensively studied and used in a variety of vascularization models. We have progressed this proven technology by deriving isolated fragments of intact human microvessels harvested from adipose (haMVs) to model human vascularization and advance human vascularized tissue models. Here we show the haMVs retain native microvessel structures, including perivascular cellularity, and recapitulate bona fide sprouting angiogenesis in vitro through distinct sprouting and neovessel elongation phases. As primary isolates, the angiogenic potential varies between donor lots and correlates with the presence of haMV perivascular cells. In an in vitro model of tumor angiogenesis, the addition of anti-tumor agents impacted tumor cell expansion in the presence of the haMVs but not endothelial cells alone demonstrating the importance of the perivascular cells in tissue modeling. The human adipose microvessels offer, in a single reagent, a more complex, dynamic human tissue model vascularization solution.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"28 2","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143564365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Correction: CCL4 contributes to aging related angiogenic insufficiency through activating oxidative stress and endothelial inflammation 更正：CCL4通过激活氧化应激和内皮炎症参与衰老相关的血管生成不足

IF 9.2 1区医学

Angiogenesis Pub Date : 2025-02-28 DOI: 10.1007/s10456-024-09964-2

Ting-Ting Chang, Liang-Yu Lin, Ching Chen, Jaw-Wen Chen

引用次数: 0

Cxcl9 modulates aging associated microvascular metabolic and angiogenic dysfunctions in subcutaneous adipose tissue Cxcl9调节皮下脂肪组织中与衰老相关的微血管代谢和血管生成功能障碍

IF 9.2 1区医学

Angiogenesis Pub Date : 2025-02-11 DOI: 10.1007/s10456-025-09970-y

Xin Fu, Yu Zhao, Xiwei Cui, Siyuan Huang, Yanze Lv, Chen Li, Fuxing Gong, Zhigang Yang, Xiaonan Yang, Ran. Xiao

{"title":"Cxcl9 modulates aging associated microvascular metabolic and angiogenic dysfunctions in subcutaneous adipose tissue","authors":"Xin Fu, Yu Zhao, Xiwei Cui, Siyuan Huang, Yanze Lv, Chen Li, Fuxing Gong, Zhigang Yang, Xiaonan Yang, Ran. Xiao","doi":"10.1007/s10456-025-09970-y","DOIUrl":"10.1007/s10456-025-09970-y","url":null,"abstract":"<div><p>Microvascular aging, predominantly driven by endothelial cells (ECs) dysfunction, is a critical early event in cardiovascular diseases. However, the specific effects of aging on ECs across the microvascular network segments and the associated mechanisms are not fully understood. In this study, we detected a microvascular rarefaction and a decreased proportion of venular ECs in the subcutaneous adipose tissue of aged mice using light-sheet immunofluorescence microscopy and single-cell RNA sequencing. Moreover, aged ECs, especially in the venular subtype, exhibited a pseudotemporal transition to a terminal state characterized by diminished oxidative phosphorylation and strengthened cytokine signaling. Metabolic flux balance analysis predicted that among the 13 differentially expressed cytokines identified in aged EC subpopulations, Cxcl9 was strongly correlated with impaired oxidative phosphorylation in aged ECs. It was further validated using microvascular ECs treated with Cxcl9. Notably, the G protein-coupled receptor signaling pathway was subsequently suppressed, in which Aplnr suppression was also observed in aged ECs, contributing to their impaired energy metabolism and reduced angiogenesis. Based on these findings, we propose Cxcl9 as a biomarker for aging-related dysfunction of microvascular ECs, suggesting that targeting Cxcl9 signaling may help combat microvascular aging.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"28 2","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-025-09970-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Correction: Neuropilin-1 controls vascular permeability through juxtacrine regulation of endothelial adherens junctions 更正：Neuropilin-1通过近肽调节内皮粘附连接来控制血管通透性

IF 9.2 1区医学

Angiogenesis Pub Date : 2025-02-04 DOI: 10.1007/s10456-024-09968-y

Sagnik Pal, Yangyang Su, Emmanuel Nwadozi, Lena Claesson-Welsh, Mark Richards

引用次数: 0

The role of liver sinusoidal endothelial cells in metabolic dysfunction-associated steatotic liver diseases and liver cancer: mechanisms and potential therapies 肝窦内皮细胞在代谢功能障碍相关的脂肪变性肝病和肝癌中的作用：机制和潜在的治疗方法

IF 9.2 1区医学

Angiogenesis Pub Date : 2025-02-03 DOI: 10.1007/s10456-025-09969-5

Hanjun Mo, Pengfei Yue, Qiaoqi Li, Yinxi Tan, Xinran Yan, Xinyue Liu, Yuanwei Xu, Yingzhe Luo, Suruiya Palihati, Cheng Yi, Hua Zhang, Minlan Yuan, Biao Yang

{"title":"The role of liver sinusoidal endothelial cells in metabolic dysfunction-associated steatotic liver diseases and liver cancer: mechanisms and potential therapies","authors":"Hanjun Mo, Pengfei Yue, Qiaoqi Li, Yinxi Tan, Xinran Yan, Xinyue Liu, Yuanwei Xu, Yingzhe Luo, Suruiya Palihati, Cheng Yi, Hua Zhang, Minlan Yuan, Biao Yang","doi":"10.1007/s10456-025-09969-5","DOIUrl":"10.1007/s10456-025-09969-5","url":null,"abstract":"<div><p>Liver sinusoidal endothelial cells (LSECs), with their unique morphology and function, have garnered increasing attention in chronic liver disease research. This review summarizes the critical roles of LSECs under physiological conditions and in two representative chronic liver diseases: metabolic dysfunction-associated steatotic liver disease (MASLD) and liver cancer. Under physiological conditions, LSECs act as selective barriers, regulating substance exchange and hepatic blood flow. Interestingly, LSECs exhibit contrasting roles at different stages of disease progression: in the early stages, they actively resist disease advancement and help restore sinusoidal homeostasis; whereas in later stages, they contribute to disease worsening. During this transition, LSECs undergo capillarization, lose their characteristic markers, and become dysfunctional. As the disease progresses, LSECs closely interact with hepatocytes, hepatic stellate cells, various immune cells, and tumor cells, driving processes such as steatosis, inflammation, fibrosis, angiogenesis, and carcinogenesis. Consequently, targeting LSECs represents a promising therapeutic strategy for chronic liver diseases. Relevant therapeutic targets and potential drugs are summarized in this review.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"28 2","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Clioquinol inhibits angiogenesis by promoting VEGFR2 degradation and synergizes with AKT inhibition to suppress triple-negative breast cancer vascularization Clioquinol通过促进VEGFR2降解抑制血管生成，并与AKT抑制协同抑制三阴性乳腺癌血管生成。

IF 9.2 1区医学

Angiogenesis Pub Date : 2025-02-03 DOI: 10.1007/s10456-024-09965-1

Yuan Gu, Tianci Tang, Moqin Qiu, Hongmei Wang, Emmanuel Ampofo, Michael D. Menger, Matthias W. Laschke

{"title":"Clioquinol inhibits angiogenesis by promoting VEGFR2 degradation and synergizes with AKT inhibition to suppress triple-negative breast cancer vascularization","authors":"Yuan Gu, Tianci Tang, Moqin Qiu, Hongmei Wang, Emmanuel Ampofo, Michael D. Menger, Matthias W. Laschke","doi":"10.1007/s10456-024-09965-1","DOIUrl":"10.1007/s10456-024-09965-1","url":null,"abstract":"<div><p>Inhibition of angiogenesis, either as monotherapy or in conjunction with other treatments, holds significant promise in cancer treatment. However, the limited efficacy of clinically approved anti-angiogenic agents underscores the urgent need for the development of novel drugs and therapeutic strategies. In this study, we demonstrate the highly selective inhibitory effects of clioquinol, a topical antifungal and antibiotic agent, on the angiogenic activity of endothelial cells (ECs) in a series of in vitro angiogenesis assays. Moreover, clioquinol effectively suppressed blood vessel formation in ex vivo aortic ring and in vivo Matrigel plug assays. Mechanistic studies revealed that clioquinol directly binds to the ATP-binding site of vascular endothelial growth factor receptor 2 (VEGFR2), promoting its degradation through both proteasome and lysosome pathways. This led to the down-regulation of the downstream extracellular signal-regulated kinase (ERK) pathway. In addition, the combination with the AKT inhibitor MK-2206 synergistically boosted the anti-angiogenic efficacy of clioquinol in vitro and in an in vivo dorsal skinfold chamber model of triple-negative breast cancer (TNBC), leading to the suppression of TNBC growth. Accordingly, clioquinol, either alone or in combination with AKT inhibitors, represents a promising therapeutic agent for future anti-angiogenic cancer treatment.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"28 2","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-024-09965-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

From bench to bedside: murine models of inherited and sporadic brain arteriovenous malformations 从实验台到床边：遗传性和散发性脑动静脉畸形的小鼠模型。

IF 9.2 1区医学

Angiogenesis Pub Date : 2025-02-03 DOI: 10.1007/s10456-024-09953-5

Ashely R. Ricciardelli, Gael Genet, Nafiisha Genet, Samuel T. McClugage III, Peter T. Kan, Karen K. Hirschi, Jason E. Fish, Joshua D. Wythe

{"title":"From bench to bedside: murine models of inherited and sporadic brain arteriovenous malformations","authors":"Ashely R. Ricciardelli, Gael Genet, Nafiisha Genet, Samuel T. McClugage III, Peter T. Kan, Karen K. Hirschi, Jason E. Fish, Joshua D. Wythe","doi":"10.1007/s10456-024-09953-5","DOIUrl":"10.1007/s10456-024-09953-5","url":null,"abstract":"<div><p>Brain arteriovenous malformations are abnormal vascular structures in which an artery shunts high pressure blood directly to a vein without an intervening capillary bed. These lesions become highly remodeled over time and are prone to rupture. Historically, brain arteriovenous malformations have been challenging to treat, using primarily surgical approaches. Over the past few decades, the genetic causes of these malformations have been uncovered. These can be divided into (1) familial forms, such as loss of function mutations in TGF-β (BMP9/10) components in hereditary hemorrhagic telangiectasia, or (2) sporadic forms, resulting from somatic gain of function mutations in genes involved in the RAS-MAPK signaling pathway. Leveraging these genetic discoveries, preclinical mouse models have been developed to uncover the mechanisms underlying abnormal vessel formation, and thus revealing potential therapeutic targets. Impressively, initial preclinical studies suggest that pharmacological treatments disrupting these aberrant pathways may ameliorate the abnormal pathologic vessel remodeling and inflammatory and hemorrhagic nature of these high-flow vascular anomalies. Intriguingly, these studies also suggest uncontrolled angiogenic signaling may be a major driver in bAVM pathogenesis. This comprehensive review describes the genetics underlying both inherited and sporadic bAVM and details the state of the field regarding murine models of bAVM, highlighting emerging therapeutic targets that may transform our approach to treating these devastating lesions.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"28 2","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-024-09953-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Anti-angiogenic therapy as potential treatment for adenomyosis 抗血管生成治疗作为子宫腺肌症的潜在治疗方法。

IF 9.2 1区医学

Angiogenesis Pub Date : 2025-01-25 DOI: 10.1007/s10456-024-09960-6

Marissa J. Harmsen, Lynda J. M. Juffermans, Muara O. Kroon, Arjan W. Griffioen, Judith A. F. Huirne

{"title":"Anti-angiogenic therapy as potential treatment for adenomyosis","authors":"Marissa J. Harmsen, Lynda J. M. Juffermans, Muara O. Kroon, Arjan W. Griffioen, Judith A. F. Huirne","doi":"10.1007/s10456-024-09960-6","DOIUrl":"10.1007/s10456-024-09960-6","url":null,"abstract":"<div><p>Adenomyosis is characterized by abnormal uterine bleeding, dysmenorrhea and subfertility. Increased expression of angiogenesis markers in adenomyosis presents a treatment opportunity and was studied in an adenomyosis mouse model. Mice were administered tamoxifen (1 mg/kg) on neonatal days 2–5. At six weeks of age, mice received oral treatment with axitinib 3 mg/kg (‘dose I/AX3’, n = 34), axitinib 25 mg/kg (‘dose II/AX25’ n = 34), or with vehicle-only (‘placebo’, n = 34). The prevalence and severity of adenomyosis were assessed. An <i>adenomyosis severity index</i> was calculated by multiplying mean grade/mouse by the percentage affected surface area. Angiogenesis-related gene expression was evaluated using real-time quantitative PCR. 101 mice completed adenomyosis induction and could be analyzed. The prevalence of adenomyosis was 30/33 (90.0%) in dose I, 29/34 (85.3%) in dose II, and 30/34 (88.2%) in placebo treated mice (p = 0.78). High grade (2/3) adenomyosis was significantly less prevalent in mice treated with axitinib dose II (n = 19, 55.9%) than in the placebo group (n = 27, 79.4%, p < 0.05). The adenomyosis severity index was reduced by 48% in the axitinib-treated groups (dose I, p < 0.05). The expression of angiogenic growth factors was reduced in the dose I and II axitinib-treated groups compared to the placebo-treated group. Following these promising first results, further research should focus on commonality among different angiostatic drugs, potential side effects, as well as the method and timing of application.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"28 1","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Ref-1 is overexpressed in neovascular eye disease and targetable with a novel inhibitor Ref-1在新生血管性眼病中过度表达，可被一种新的抑制剂靶向

IF 9.2 1区医学

Angiogenesis Pub Date : 2025-01-05 DOI: 10.1007/s10456-024-09966-0

Anbukkarasi Muniyandi, Gabriella D. Hartman, Kamakshi Sishtla, Ratan Rai, Cátia Gomes, Kristina Day, Yang Song, Andi R. Masters, Sara K. Quinney, Xiaoping Qi, Hailey Woods, Michael E. Boulton, Jason S. Meyer, Jonah Z. Vilseck, Millie M. Georgiadis, Mark R. Kelley, Timothy W. Corson

{"title":"Ref-1 is overexpressed in neovascular eye disease and targetable with a novel inhibitor","authors":"Anbukkarasi Muniyandi, Gabriella D. Hartman, Kamakshi Sishtla, Ratan Rai, Cátia Gomes, Kristina Day, Yang Song, Andi R. Masters, Sara K. Quinney, Xiaoping Qi, Hailey Woods, Michael E. Boulton, Jason S. Meyer, Jonah Z. Vilseck, Millie M. Georgiadis, Mark R. Kelley, Timothy W. Corson","doi":"10.1007/s10456-024-09966-0","DOIUrl":"10.1007/s10456-024-09966-0","url":null,"abstract":"<div><p>Reduction–oxidation factor-1 or apurinic/apyrimidinic endonuclease 1 (Ref-1/APE1) is a crucial redox-sensitive activator of transcription factors such as NF-κB, HIF-1α, STAT-3 and others. It could contribute to key features of ocular neovascularization including inflammation and angiogenesis; these underlie diseases like neovascular age-related macular degeneration (nAMD). We previously revealed a role for Ref-1 in the growth of ocular endothelial cells and in choroidal neovascularization (CNV). Here, we set out to further explore Ref-1 in neovascular eye disease. Ref-1 was highly expressed in human nAMD, murine laser-induced CNV and <i>Vldlr</i><sup>−/−</sup> mouse subretinal neovascularization (SRN). Ref-1’s interaction with a redox-specific small molecule inhibitor, APX2009, was shown by NMR and docking. This compound blocks crucial angiogenic features in multiple endothelial cell types. APX2009 also ameliorated murine laser-induced choroidal neovascularization (L-CNV) when delivered intravitreally. Moreover, systemic APX2009 reduced murine SRN and downregulated the expression of Ref-1 redox regulated HIF-1α target carbonic anhydrase 9 (CA9) in the <i>Vldlr</i><sup>−/−</sup> mouse model. Our data validate the redox function of Ref-1 as a critical regulator of ocular angiogenesis, indicating that inhibition of Ref-1 holds therapeutic potential for treating nAMD.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"28 1","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

A novel quantitative angiogenesis assay based on visualized vascular organoid 一种基于可视化血管类器官的新型定量血管生成实验

IF 9.2 1区医学

Angiogenesis Pub Date : 2025-01-03 DOI: 10.1007/s10456-024-09967-z

Yun Zhao, Mengze Sun, Zihang Pan, Weijing Kong, Zixuan Hong, Wei Zhang, Bingbing Sun, Jingjing Zhang, Xi Wang, Kai Wang

引用次数: 0