Angiogenesis最新文献_第4页

Critical role of endothelial regulator of G protein signaling 5 in postnatal angiogenesis 内皮调节因子G蛋白信号5在出生后血管生成中的关键作用

IF 11.2 1区医学

Angiogenesis Pub Date : 2026-08-01 DOI: 10.1007/s10456-026-10079-z

Nikola Sladojevic, Haw-Chih Tai, Dhiraj Patel, Maryam Emami, James K. Liao

{"title":"Critical role of endothelial regulator of G protein signaling 5 in postnatal angiogenesis","authors":"Nikola Sladojevic, Haw-Chih Tai, Dhiraj Patel, Maryam Emami, James K. Liao","doi":"10.1007/s10456-026-10079-z","DOIUrl":"10.1007/s10456-026-10079-z","url":null,"abstract":"<div><h3>Aims</h3><p>Regulator of G protein signaling 5 (RGS5) modulates G-protein coupled receptor (GPCR) signaling and is markedly upregulated in angiogenesis. However, its function in endothelial cells and its role in mediating postnatal angiogenesis remain unclear. The purpose of this study is to define the role of endothelial RGS5 in regulating VEGF signaling and angiogenesis.</p><h3>Methods and results</h3><p>In a hindlimb ischemia model, we found impaired postnatal angiogenesis, reduced perfusion recovery, and increased rates of auto-amputation in mice with either global or endothelial-specific deletion of <i>Rgs5</i>. <i>Rgs5</i> deficiency in ECs led to reduced VEGFR2 phosphorylation at Tyr<sup>1175</sup> and its downstream signaling pathways. This was accompanied by increased activity of the tyrosine phosphatase, SHP-1, which dephosphorylates and inactivates VEGFR2. In vitro, <i>Rgs5</i>-deficient ECs exhibited diminished migration, increased apoptosis, and reduced viability in response to VEGF stimulation. These findings indicate that RGS5 is essential for maintaining VEGF-mediated angiogenic signaling through inhibition of SHP-1 activity.</p><h3>Conclusion</h3><p>Endothelial RGS5 is a critical regulator of VEGF signaling and postnatal angiogenesis. By attenuating SHP-1–mediated dephosphorylation of VEGFR2, RGS5 preserves VEGF signaling and angiogenesis. Targeting the RGS5–SHP-1 axis may be a useful therapeutic strategy for improving angiogenesis in response to ischemia.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 4","pages":""},"PeriodicalIF":11.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-026-10079-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148652311","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

Endothelial VEGFR2 insufficiency promotes the transition of lymphatic to hematopoietic transcriptional programs 内皮细胞VEGFR2不足促进淋巴转录程序向造血转录程序的转变。

IF 11.2 1区医学

Angiogenesis Pub Date : 2026-07-26 DOI: 10.1007/s10456-026-10081-5

Taotao Li, Xudong Cao, Fei Zhou, Xiujuan Li, Wenjuan Ma, Xiuyan Zhang, Haoyu Zhong, Beibei Xu, Man Chu, Xiwen Jia, Kai Ding, Xin Shen, Yahui Liu, Yun Zhao, Zhen Zhang, Junhao Hu, Young-Kwon Hong, Lena Claesson-Welsh, Yulong He

{"title":"Endothelial VEGFR2 insufficiency promotes the transition of lymphatic to hematopoietic transcriptional programs","authors":"Taotao Li, Xudong Cao, Fei Zhou, Xiujuan Li, Wenjuan Ma, Xiuyan Zhang, Haoyu Zhong, Beibei Xu, Man Chu, Xiwen Jia, Kai Ding, Xin Shen, Yahui Liu, Yun Zhao, Zhen Zhang, Junhao Hu, Young-Kwon Hong, Lena Claesson-Welsh, Yulong He","doi":"10.1007/s10456-026-10081-5","DOIUrl":"10.1007/s10456-026-10081-5","url":null,"abstract":"<div><p>Vascular endothelial growth factor receptor-2 (VEGFR2) is a key target for regulating the endothelial cell lineage and angiogenesis. It is also expressed by lymphatic endothelial cells (LECs) while its participation in lymphangiogenesis remains inadequately characterized. We demonstrate in this study that VEGFR2 is highly expressed in dermal initial lymphatic vessels and valves. The induced deletion of pan-endothelial <i>Vegfr2</i> at the neonatal stage produced a potent suppression of dermal lymphatic growth, characterized by a thinner lymphatic diameter, a decreased number of LECs and lymphatic valves. Mechanistically, VEGFR2 insufficiency led to a dramatic decrease in lymphatic VEGFR3, a key regulator mediating signals for lymphatic growth and remodeling. RNA sequencing analysis revealed that GO terms enriched for downregulated genes included biological processes related to EC development while pathways related to hematopoiesis and immune responses were upregulated in the skin of <i>Vegfr2</i> mutants compared with littermate controls. This was further confirmed by RNA-seq analysis of dermal tissues 48 h after endothelial <i>Vegfr2</i> deletion. Consistently, targeting <i>Vegfr2</i> in PROX1<sup>+</sup> cells produced an inhibitory effect on dermal lymphatic growth and recapitulated a similar altered transcriptomic signature. The alteration of lymphatic gene expression was further validated by siRNA-mediated <i>Vegfr2</i> knockdown in primary LECs, showing a transcriptional trend toward a hematopoietic fate. Findings from this study imply that VEGFR2 is required for the maintenance of endothelial identity, and its insufficiency triggers a transcriptional reprogramming that diminishes VEGFR3-mediated lymphangiogenesis.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 3","pages":""},"PeriodicalIF":11.2,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590240","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

Endothelial protein C receptor and the endothelial progenitor paradigm: towards a functional definition at last 内皮蛋白C受体和内皮祖细胞范式：最终走向功能定义。

IF 11.2 1区医学

Angiogenesis Pub Date : 2026-06-30 DOI: 10.1007/s10456-026-10069-1

David M. Smadja

引用次数: 0

Endothelial Notch1 drives multicellular remodelling during hyaloid vessel regression 内皮Notch1在玻璃体血管退化过程中驱动多细胞重构。

IF 11.2 1区医学

Angiogenesis Pub Date : 2026-06-30 DOI: 10.1007/s10456-026-10062-8

Shaymaa Khazaal, Abdoul-Razak Sango, Kawtar Zouine, Alexa Silva Sosa, Ariane Vanessa Megne, Rony Chidiac, Kiran Bora, Gaelle Mawambo, Jing Chen, Malika Oubaha

{"title":"Endothelial Notch1 drives multicellular remodelling during hyaloid vessel regression","authors":"Shaymaa Khazaal, Abdoul-Razak Sango, Kawtar Zouine, Alexa Silva Sosa, Ariane Vanessa Megne, Rony Chidiac, Kiran Bora, Gaelle Mawambo, Jing Chen, Malika Oubaha","doi":"10.1007/s10456-026-10062-8","DOIUrl":"10.1007/s10456-026-10062-8","url":null,"abstract":"<div><p>Hyaloid vessel regression is essential for vitreous transparency and normal vision, yet how this transient vascular network is dismantled remains unclear. Here we show that postnatal hyaloid regression in mice is not driven by a measurable increase in apoptosis, but instead by coordinated endothelial and mural cell delamination, extravascular redistribution and a transient plasticity program marked by Snail1 and Slug induction. Notch1 signalling peaks during the regression window, and vascular endothelial-specific Notch1 deletion causes persistent hyaloid vessels, with excessive proliferation and failure of endothelial and mural cell disengagement. Mechanistically, loss of Notch1 preserves endothelial identity, suppresses an endothelial-mesenchymal transition-like transcriptional program and reduces expression of the Wnt co-recepteors <i>Lrp5</i> and <i>Lrp6</i>. Wnt pathway mutant phenocopies the delamination defect, supporting functional convergence between Notch1 and Wnt signalling during vessel involution. Together, these findings identify Notch1 as a key driver of developmental vascular pruning. They also redefine hyaloid regression as an apoptosis-non-exclusive remodelling process, with broader implications for physiological and pathological vascular remodelling, and may guide therapeutic strategies to modulate vascular regression in ocular disorders.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 3","pages":""},"PeriodicalIF":11.2,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-026-10062-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148349901","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

Tumour endothelial cell reprogramming orchestrates angiocrine signalling to drive chemoresistance in breast cancer 肿瘤内皮细胞重编程协调血管分泌信号驱动乳腺癌化疗耐药。

IF 11.2 1区医学

Angiogenesis Pub Date : 2026-06-22 DOI: 10.1007/s10456-026-10063-7

Jesus Gomez-Escudero, Eleni Maniati, Julie Holdsworth, Gordon Beattie, Maruan Hijazi, Matt Guelbert, Samar Elorbany, Pedro Cutillas, Jun Wang, Kairbaan Hodivala-Dilke, Gabriela D’Amico

{"title":"Tumour endothelial cell reprogramming orchestrates angiocrine signalling to drive chemoresistance in breast cancer","authors":"Jesus Gomez-Escudero, Eleni Maniati, Julie Holdsworth, Gordon Beattie, Maruan Hijazi, Matt Guelbert, Samar Elorbany, Pedro Cutillas, Jun Wang, Kairbaan Hodivala-Dilke, Gabriela D’Amico","doi":"10.1007/s10456-026-10063-7","DOIUrl":"10.1007/s10456-026-10063-7","url":null,"abstract":"<div><p>Despite its established role in breast cancer treatment, Doxorubicin treatment remains subject to adaptive resistance mechanisms that extend beyond cancer cell intrinsic alterations ultimately reducing therapy efficacy. Our study in a MMTV-PyMT-driven mouse breast cancer model reveals that prolonged Doxorubicin (Dox) exposure triggers significant reprogramming of the tumour vasculature, substantially altering the angiocrine landscape and shaping treatment outcomes. Notably, tumours that initially respond, but later revert, display an endothelial cell subclustering with activation of proliferative and NF-κB-dependent cytokine pathways. We further identify a novel endothelial subpopulation characterised by higher expression of drug clearance and oxidative metabolism markers, suggesting an active role in mitigating Dox efficacy and angiogenesis promotion. These findings substantiate endothelial plasticity as a critical mediator of therapeutic failure. By uncovering these vascular adaptations, our work provides a new perspective on the underlying mechanisms of Dox resistance and the prolonged efficacy of chemotherapy in breast cancer.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 3","pages":""},"PeriodicalIF":11.2,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-026-10063-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293204","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

A possible microvascular vulnerability in carotid artery dissection: insights from nailfold capillaroscopy 颈动脉夹层中可能存在的微血管易损：来自甲襞毛细血管镜的见解。

IF 11.2 1区医学

Angiogenesis Pub Date : 2026-06-19 DOI: 10.1007/s10456-026-10066-4

Angelo Nigro, Sandro Sanguigni, Giuseppe Nicoletti

引用次数: 0

From endothelial epigenetic switching to a vascular-readiness compass for cancer immunotherapy 从内皮表观遗传转换到癌症免疫治疗的血管准备罗盘。

IF 11.2 1区医学

Angiogenesis Pub Date : 2026-06-15 DOI: 10.1007/s10456-026-10065-5

M. Vijayasimha, M. Srikanth, Keerthi Rao

引用次数: 0

MCC links Wnt/PCP signaling to endothelial polarity and vascular remodeling MCC将Wnt/PCP信号与内皮极性和血管重构联系起来。

IF 11.2 1区医学

Angiogenesis Pub Date : 2026-06-15 DOI: 10.1007/s10456-026-10068-2

Valentin Delobel, Béatrice Jaspard, Malvina Salami, Marion Camoin, Claire Peghaire, Juliette Vaurs, Romain Boulestreau, Alexandre Dubrac, Thierry Couffinhal, Cécile Duplàa

{"title":"MCC links Wnt/PCP signaling to endothelial polarity and vascular remodeling","authors":"Valentin Delobel, Béatrice Jaspard, Malvina Salami, Marion Camoin, Claire Peghaire, Juliette Vaurs, Romain Boulestreau, Alexandre Dubrac, Thierry Couffinhal, Cécile Duplàa","doi":"10.1007/s10456-026-10068-2","DOIUrl":"10.1007/s10456-026-10068-2","url":null,"abstract":"<div><p>Vascular remodeling is crucial for establishing a functional vasculature and maintaining organ homeostasis. In the central nervous system (CNS), Wnt signaling plays a critical role in guiding endothelial cell (EC) behavior during vascular development and specialization. While canonical Wnt/β-catenin signaling regulates endothelial specification and blood–brain barrier formation, the non-canonical Wnt/Planar Cell Polarity (PCP) pathway orchestrates vascular remodeling and flow adaptation. However, how PCP signaling is transduced into intracellular polarity control remains unknown. Here, we identify MCC (Mutated in Colorectal Cancer) as a key regulator of endothelial polarity and migration downstream of the Wnt/PCP signaling pathway. Mechanistically, MCC interacts with the centriolar satellite protein CEP131 and promotes its turnover through proteasome- and autophagy-dependent pathways, thereby maintaining centrosome-associated organization required for directional polarity. MCC depletion disrupts directional polarity while preserving and enhancing flow-induced cytoskeletal elongation, revealing a functional dissociation between alignment and front–rear polarization. In vivo, endothelial-specific deletion of <i>Mcc</i> in the postnatal retina impairs vascular remodeling, reduces endothelial proliferation, and disrupts polarity at the angiogenic front. Notably, normalization of vascular density and regression by captopril does not restore polarity, indicating a cell-intrinsic role for MCC in endothelial organization. Together, these findings uncover an MCC–CEP131 axis linking Wnt/PCP signaling to centrosome-associated proteostasis and identify MCC as a key coordinator of endothelial polarity during vascular remodeling.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 3","pages":""},"PeriodicalIF":11.2,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248952","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

miR-150 controls developmental angiogenesis via ribosome biogenesis-dependent regulation of Notch signaling miR-150通过核糖体生物发生依赖性调节Notch信号来控制发育性血管生成。

IF 11.2 1区医学

Angiogenesis Pub Date : 2026-06-15 DOI: 10.1007/s10456-026-10067-3

Haotian Kong, Kang Ai, Jinghe Zhang, Ziting Liu, Yue Wu, Li Zhang, Huixin Zhang, Xiuli Chen, Linglu Li, Yuanyuan Fu, Xiaojing Wang, Lei Li

{"title":"miR-150 controls developmental angiogenesis via ribosome biogenesis-dependent regulation of Notch signaling","authors":"Haotian Kong, Kang Ai, Jinghe Zhang, Ziting Liu, Yue Wu, Li Zhang, Huixin Zhang, Xiuli Chen, Linglu Li, Yuanyuan Fu, Xiaojing Wang, Lei Li","doi":"10.1007/s10456-026-10067-3","DOIUrl":"10.1007/s10456-026-10067-3","url":null,"abstract":"<div><p>The development of a functional vasculature is controlled by the coordination of various mechanisms. Key molecules and signaling pathways regulating vascular development remain far from understood. Here, we demonstrate that <i>miR-150</i> is highly enriched in zebrafish vascular endothelial cells (ECs), and plays a key role in regulating developmental angiogenesis during embryogenesis. Depletion of <i>miR-150</i> impairs intersegmental vessel (ISV) sprouting, whereas EC-overexpression of <i>miR-150</i> induces ectopic vascular sprouting. Mechanistically, <i>miR-150</i> binds to the 3’UTR of zebrafish <i>wdr75</i> to modulate ribosome biogenesis. Loss of <i>miR-150</i> led to upregulated ribosome biogenesis, which enhanced Notch signaling activity and inhibited developmental angiogenesis. Pharmacological inhibition of ribosome biogenesis or Notch signaling effectively rescued the angiogenic defects in <i>miR-150-</i>deficient embryos. These findings establish <i>miR-150</i> as a key regulator of developmental angiogenesis through modulation of ribosome biogenesis and downstream Notch signaling during zebrafish embryogenesis.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 3","pages":""},"PeriodicalIF":11.2,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248940","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

Endothelial AGO1 deficiency reduces breast cancer burden in mice 内皮细胞AGO1缺乏可减轻小鼠乳腺癌负担

IF 9.2 1区医学

Angiogenesis Pub Date : 2026-06-12 DOI: 10.1007/s10456-026-10048-6

Xuejing Liu, Alonso Tapia, Dongqiang Yuan, Xiaofang Tang, Yingjun Luo, Naseeb Kaur Malhi, Muxi Chen, Kwan Ho Law, Mohamad Haidar, Skylar Giacobetti, Jiawei Sun, Anthony Park, Saul J. Priceman, Zhen Bouman Chen

{"title":"Endothelial AGO1 deficiency reduces breast cancer burden in mice","authors":"Xuejing Liu, Alonso Tapia, Dongqiang Yuan, Xiaofang Tang, Yingjun Luo, Naseeb Kaur Malhi, Muxi Chen, Kwan Ho Law, Mohamad Haidar, Skylar Giacobetti, Jiawei Sun, Anthony Park, Saul J. Priceman, Zhen Bouman Chen","doi":"10.1007/s10456-026-10048-6","DOIUrl":"10.1007/s10456-026-10048-6","url":null,"abstract":"<div><p>Endothelial cells (ECs) are crucial in cancer development and progression, partly by regulating tumor angiogenesis and immune modulation. As a key component of the RNA-induced silencing complex, Argonaute 1 (AGO1) regulates tumor biology, yet the specific function of AGO1 within ECs in the tumor microenvironment remains undefined. Here, we investigated the effects of endothelial-specific AGO1 knockout (EC-AGO1-KO) on tumor vascularization and immune regulation in a mouse syngeneic breast cancer model induced by E0771 cells. EC-AGO1-KO mice exhibited significantly reduced tumor burden compared to their wild-type (WT) littermates, accompanied by reduced vascularization and enhanced immune cell infiltration. Histological and single-cell RNA sequencing analyses revealed increased infiltration of CD8⁺ T cells and macrophages in EC-AGO1-KO tumors, indicative of an immunostimulatory microenvironment. In vitro, AGO1 knockdown in mouse ECs co-cultured with E0771 tumor cells led to higher levels of <i>Cxcl10</i> and <i>Vcam1</i> expression, suggesting a pro-inflammatory and leukocyte-recruiting effect. Together, these findings identify endothelial AGO1 as a key regulator of tumor vasculature and immune homeostasis in breast cancer, suggesting that targeting endothelial AGO1 may represent a novel therapeutic strategy to modulate tumor vasculature while enhancing anti-tumor immunity.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 3","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-026-10048-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148237008","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