Angiogenesis最新文献

{"title":"Pathophysiology of endothelial dysfunction in Fontan circulation: from bench to bedside and back again","authors":"Amalia Baroutidou,&nbsp;Artemios G. Karagiannidis,&nbsp;Theodoros Dimitroulas,&nbsp;Vasileios Kamperidis,&nbsp;Antonios Ziakas,&nbsp;Konstantinos Dimopoulos,&nbsp;George Giannakoulas","doi":"10.1007/s10456-025-09996-2","DOIUrl":"10.1007/s10456-025-09996-2","url":null,"abstract":"<div><p>The Fontan procedure is a definitive surgical approach for complex cardiac malformations, redirecting systemic venous blood into the pulmonary circulation through a staged repair that separates systemic and pulmonary venous returns in the absence of a subpulmonary ventricle. The ensuing unique hemodynamic conditions compromise the endothelial function both in the pulmonary and the systemic circulation. The underlying pathophysiological mechanisms, although distinct within each vascular bed, are interrelated and may collectively contribute to progressive end-organ dysfunction, ultimately accounting for the significant morbidity burden in Fontan patients. This review provides an overview of the current knowledge on the pathophysiology of pulmonary and systemic vasculopathy in Fontan circulation, with particular emphasis on the interplay between endothelial dysfunction and adverse clinical outcomes. Remaining gaps in knowledge and directions of future research are also discussed.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"28 4","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-025-09996-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144888020","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}

{"title":"MY-1 promotes angiogenesis in the ischemic hindlimbs by regulating the stability of CDC42 via PSMD14","authors":"Xian Ding,&nbsp;Yuxin Zhang,&nbsp;Yuting Zeng,&nbsp;Qianlin Li,&nbsp;Sijie Qiu,&nbsp;Ping Xiao,&nbsp;Xin Luo,&nbsp;Jiaping Chen,&nbsp;Qianwen Deng,&nbsp;Dehong Yang,&nbsp;Yanli Zhang,&nbsp;Wenjuan Yan","doi":"10.1007/s10456-025-09989-1","DOIUrl":"10.1007/s10456-025-09989-1","url":null,"abstract":"<div><p>Critical limb ischemia (CLI) is a refractory peripheral artery disease characterized by tissue ischemia, presenting significant therapeutic challenges. Current surgical revascularization treatments are limited by indications, complications, and other constraints, making the identification of novel therapeutic strategies an important objective for CLI management. In this study, we designed and synthesized a novel short peptide, named MY-1, and developed a GelMA/MY-1 hydrogel sustained-release system for local application in a mouse hindlimb ischemia model. This system significantly promoted blood flow reperfusion and muscle tissue repair in the ischemic region. In vitro experiments revealed that MY-1 promoted the formation of filopodia in endothelial cells, accelerating cell migration and confirming the critical role of CDC42 in this process. Importantly, we found that MY-1 regulates the stability of CDC42, driving endothelial cell dynamics. Building on this, we identified PSMD14 as a novel upstream target influencing CDC42 stability. Silencing PSMD14 impaired filopodia formation, migration ability, and CDC42 stability in endothelial cells, and MY-1 could not reverse these effects. This indicates the potential of MY-1 in regulating deubiquitinase activity in angiogenesis.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"28 4","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144868915","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}

{"title":"RE: acute aortic dissection in a patient with hereditary hemorrhagic telangiectasia associated with juvenile polyposis due to SMAD4 mutation","authors":"Ehab Y. Harahsheh,&nbsp;George Bcharah,&nbsp;Misha B. Asif,&nbsp;Linnea M. Baudhuin,&nbsp;Pavel Pichurin,&nbsp;Fadi Shamoun,&nbsp;Mayowa A. Osundiji","doi":"10.1007/s10456-025-09999-z","DOIUrl":"10.1007/s10456-025-09999-z","url":null,"abstract":"","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"28 4","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788090","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}

{"title":"Angiopoietin-2 binds to FGFR2, inhibits FGF-FGFR2 signaling, and delays cutaneous wound healing by inhibiting wound angiogenesis","authors":"Minji Sim,&nbsp;Hidetaka Ohnuki,&nbsp;Stewart Durell,&nbsp;Haydar Bulut,&nbsp;Yuyi Wang,&nbsp;Marzena Dyba,&nbsp;Sergey G. Tarasov,&nbsp;Lisa M. Jenkins,&nbsp;Giovanna Tosato","doi":"10.1007/s10456-025-09988-2","DOIUrl":"10.1007/s10456-025-09988-2","url":null,"abstract":"<div><p>Wound healing is an essential repair process, and impaired wound healing is a common and sometimes debilitating medical problem. Despite advances in wound healing approaches, optimal management strategies are lacking, partly due to an incomplete understanding of the complex pathophysiology of this process. Here we show that Ang2, a previously known ligand for the Tie2 receptor, also binds to fibroblast growth factor receptor 2 (FGFR2) independently of Tie2 and attenuates FGF/FGFR2 signaling in endothelial cells. Functionally, Ang2 inhibits endothelial cell migration induced by FGF. In mouse, topical Ang2 delays the healing of skin wounds, associated with reduced wound angiogenesis and recruitment of mesenchymal-type cells. Additionally, topical AMG386, a blocker of Ang1/Ang2 binding to Tie2 and systemic REGN910, a blocker of Ang2 binding to Tie2, accelerate wound repair, associated with increased wound angiogenesis and recruitment of inflammatory cells. These results identify the tyrosine kinase FGFR2 as a previously unrecognized Ang2 receptor, explaining some of the context-dependent functions of Ang2 in endothelial cells. Since Ang2 is induced in cutaneous wounds and endogenous FGF/FGFR2 is essential for wound repair, Ang2 blockade holds promise as a new evidence-based therapeutic option to promote wound repair.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"28 4","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12325526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788089","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}

{"title":"UHRF1 in endothelial cells is essential for angiogenesis and associated with the activation of pro-angiogenic signaling pathways and expression of endothelial genes","authors":"Ying Liu,&nbsp;Jiake Mo,&nbsp;Zi Guo,&nbsp;Jiaqi Zhang,&nbsp;Weian Tang,&nbsp;Xubiao Meng,&nbsp;Yufang Luo,&nbsp;Fang Wang,&nbsp;Zhaohui Mo","doi":"10.1007/s10456-025-09998-0","DOIUrl":"10.1007/s10456-025-09998-0","url":null,"abstract":"<div><p>Epigenetics is increasingly recognized as a crucial factor in angiogenesis. Ubiquitin-like with PHD and RING Finger Domains 1 (UHRF1) is an important epigenetic regulatory protein involved in regulating cellular life processes, developing many diseases. However, its potential role in regulating embryonic vascular development and postnatal angiogenesis is unclear. Our study found that endothelial cell-specific UHRF1 knockout mice showed obvious developmental disorders at the embryonic stage (E11.5-15.5), including impaired development of the individual embryo size and organs, sparse vascularity in the yolk sac, or even death. In the lower limb ischemia model, UHRF1 expression in ischemic muscle tissues of mice is proportionate to the regeneration of blood vessels. To confirm the specific inhibition of UHRF1, we transfected an adeno-associated virus serotype 9 which inserted a TIE-2 promoter and mediated the delivery of short hairpin RNA (AAV9-TIE-2-shUHRF1) into mouse vascular endothelial cells to knock down UHRF1 specifically. We observed that the knockdown of UHRF1 in endothelial cells results in poorer lower limb perfusion in mice. Mechanically, UHRF1 knockdown decreased the tube-forming capacity of ECFCs, whereas overexpression of UHRF1 by diabetic ECFCs where UHRF1 expression is typically downregulated significantly increased the tube-forming capacity of the cells. RNAseq and related bioinformatics analyses showed that differentially expressed genes (DEGs) were mainly involved in angiogenesis-related pathways. The results of qPCR and western blot showed that the protein and mRNA levels of angiogenesis-related factors (VEGF, PDGF, and ANGPT1), as well as vascular endothelial surface marker molecules (VEGFR2, CD31, and c-Kit), were down-regulated accordingly. Furthermore, ChIP experiments showed that UHRF1 was able to bind the promoters of VEGFR2 and CD31, affecting the levels of histone-methylated protein (H3K4me3 and H3K27me3) enriched in the promoter region. However, the expression of CD31 and VEGFR2 can be reversed separately after the transformation of different histone-methylated protein levels (H3K4me3 and H3K27me3). Taken together, UHRF1 may regulate angiogenic gene expression and vascular endothelial cell differentiation through epigenetic mechanisms and is essential for angiogenesis.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"28 4","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788091","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}

{"title":"In vivo profiling of the endothelium using ‘AngioTag’ zebrafish","authors":"Mayumi F. Miller,&nbsp;Leah J. Greenspan,&nbsp;Derek E. Gildea,&nbsp;Kathryn Monzo,&nbsp;Gennady Margolin,&nbsp;Van N. Pham,&nbsp;Keith K. Ameyaw,&nbsp;Lisa Price,&nbsp;Natalie Aloi,&nbsp;Amber N. Stratman,&nbsp;Andrew E. Davis,&nbsp;Isabella Cisneros,&nbsp;Caleb A. Mertus,&nbsp;Ryan K. Dale,&nbsp;Andreas D. Baxevanis,&nbsp;Brant M. Weinstein","doi":"10.1007/s10456-025-09990-8","DOIUrl":"10.1007/s10456-025-09990-8","url":null,"abstract":"<div><p>Vascular endothelial cells in vivo are exquisitely regulated by their local environment, which is disrupted or absent when using methods such as FACS sorting of cells isolated from animals or in vitro cell culture. Here, we profile the gene expression patterns of undisturbed endothelial cells in living animals using a novel “AngioTag” zebrafish transgenic line that permits isolation of actively translating mRNAs from endothelial cells in their native environment. This transgenic line uses the endothelial cell-specific <i>kdrl</i> promoter to drive expression of an epitope tagged Rpl10a 60 S ribosomal subunit protein, allowing for Translating Ribosome Affinity Purification (TRAP) of actively translating endothelial cell mRNAs. By performing TRAP-RNAseq on AngioTag animals, we demonstrate strong enrichment of endothelial-specific genes and have uncovered both novel endothelial genes and unique endothelial gene expression signatures for different adult organs. Finally, we generated a versatile “UAS: RiboTag” transgenic line to allow a wider array of different zebrafish cell and tissue types to be examined using TRAP-RNAseq methods. These new tools offer an unparalleled resource to study the molecular identity of cells in their normal in vivo context.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"28 3","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558871","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}

{"title":"Semaphorin 3A protects against thoracic aortic aneurysm dissection by suppressing aortic angiogenesis","authors":"Li-Fei Wu,&nbsp;Jiao-Jiao Zhang,&nbsp;Xing Zhang,&nbsp;De-Ping Wang,&nbsp;Zhi-Fa Zheng,&nbsp;Jing Shen,&nbsp;Ying Zhou,&nbsp;Li-Juan Gao,&nbsp;Xuan Shang,&nbsp;Jun-Ya Ning,&nbsp;Qing-Hua Liu,&nbsp;Lan Zhou,&nbsp;Zhang-Rong Jia,&nbsp;Jia-Song Chang,&nbsp;Jian-Yun Shi,&nbsp;Shuang Wang,&nbsp;Teng Sun,&nbsp;Xue-Ning Wang,&nbsp;Zhi-Fang Wu,&nbsp;Si-Jin Li,&nbsp;Xin Zhou,&nbsp;Ji-Min Cao","doi":"10.1007/s10456-025-09992-6","DOIUrl":"10.1007/s10456-025-09992-6","url":null,"abstract":"<div><p>Thoracic aortic aneurysm (TAA) is life-threatening once developing to sudden dissection (TAAD) or rupture. The pathogenesis of TAA remains poorly understood and there is no effective pharmacologic therapy. Increased aortic angiogenesis has been recognized as a key factor contributing to TAA formation, yet the regulatory mechanisms governing this process remain unclear. Here we found that the mRNA and protein levels of Sema3A were significantly decreased in human TAA/TAAD tissues compared to non-TAA aortic tissues. Global or vascular smooth muscle cells (VSMCs)-specific overexpression of Sema3A significantly alleviated the progression of β-aminopropionitrile fumarate (BAPN)-induced TAA and reduced TAAD incidence, whereas VSMCs-specific knockout of Sema3A aggravated TAA and increased TAAD incidence, in mice. Sema3A was leadingly expressed in the VSMCs, and the VSMCs-derived Sema3A protected TAA mainly via binding to NRP1 on the endothelial cells (ECs) and inhibiting the downstream ERK signaling, and thereby suppressing aortic neovascularization, inflammation and extracellular matrix (ECM) degradation. Administration of recombinant Sema3A protein hindered TAA progression and reduced TAAD incidence in mice. In summary, we demonstrated that Sema3A is a potential endogenous protective factor for TAA. Downregulation of Sema3A promotes TAA progression and TAAD attack, whereas upregulation of Sema3A or administration of recombinant Sema3A protein alleviates TAA and reduces TAAD incidence. The protection of Sema3A on TAA depends on the VSMC-EC crosstalk and activation of endothelial NRP1-ERK signaling, and thereby the suppression of angiogenesis and angiogenesis-associated inflammation and ECM degradation.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"28 3","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526129","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}

{"title":"Mechanistic insights into endometriosis: roles of Streptococcus agalactiae and L-carnitine in lesion development and angiogenesis","authors":"Yuan Zhuang,&nbsp;Ting Lyu,&nbsp;Yang Chen,&nbsp;Wei Li,&nbsp;Lei Tang,&nbsp;Shi-ping Xian,&nbsp;Peng-fei Yang,&nbsp;Lijie Wang,&nbsp;Qian-qian Zhang,&nbsp;Chaoming Mei,&nbsp;Yu-jing Lin,&nbsp;Zhixiang Yan,&nbsp;Zhanyu Li,&nbsp;Jian-zhong He,&nbsp;Fa-min Zeng","doi":"10.1007/s10456-025-09991-7","DOIUrl":"10.1007/s10456-025-09991-7","url":null,"abstract":"<div><p>Retrograde menstruation is a widely recognized etiological factor for endometriosis (EMs); however, it is not the sole cause, as not all affected women develop EMs. Emerging evidence suggests a significant association between the vaginal microbiota and EMs. Nonetheless, the precise mechanisms by which microbial communities influence the pathophysiology and progression of EMs remain unclear. In this study, the cervical mucus from patients with EMs showed significantly greater microbial abundance compared with that of controls, with <i>Streptococcus agalactiae</i> (<i>S. agalactiae</i>) exhibiting the most substantial increase as determined by 16S rRNA gene sequencing. In a murine model, elevated <i>S. agalactiae</i> levels significantly increased the lesion number and colonization, whereas antibiotic treatment reduced lesion formation. Metabolomic analyses showed elevated L-carnitine levels in the cervical secretions and serum of patients with EMs, a finding corroborated in murine tissues. Exogenous L-carnitine administration similarly increased the number and weight of endometriotic lesions. Meanwhile, the inhibition of L-carnitine synthesis suppressed lesion formation induced by <i>S. agalactiae</i>. In vitro, both <i>S. agalactiae</i> and L-carnitine promoted EMs cell proliferation, migration, and invasion. L-carnitine synthesis inhibition attenuated cell motility stimulated by <i>S. agalactiae</i>. Mechanistically, <i>S. agalactiae</i> enhanced angiogenesis through L-carnitine by upregulating vascular endothelial growth factor expression and increasing human umbilical vein endothelial cell motility. These findings identify <i>S. agalactiae</i> as a key cervical microbiome component in EMs development and reveal a microbiota–metabolite–angiogenesis axis that may offer novel therapeutic targets.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"28 3","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482906","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}

{"title":"Proteoglycans and glycosaminoglycans: critical regulators in angiogenesis, vasculogenesis, and vascularized tissue engineering","authors":"Binbin Lin,&nbsp;Tianyu Sun,&nbsp;Yiqi Feng,&nbsp;Hongyu Liu,&nbsp;Lingling Zhang,&nbsp;Buling Wu,&nbsp;Jingyi Wu","doi":"10.1007/s10456-025-09995-3","DOIUrl":"10.1007/s10456-025-09995-3","url":null,"abstract":"<div><p>Reconstruction of the microvascular network is essential for tissue regeneration and functional repair. However, inadequate vascularization remains an arduous challenge, hindering graft survival in wound healing and regenerative medicine. Although neovascularization and vascularized tissue engineering have received considerable attention, current investigations into the regulatory mechanisms of microvascular regeneration have primarily focused on intracellular signaling entities, leaving the extracellular molecular-level regulatory mechanisms unclear. Proteoglycans (PGs), ubiquitously distributed in the extracellular matrix and on cell membranes, consist of glycosaminoglycan (GAG) chains covalently linked to core proteins. Their spatiotemporal heterogeneity enables precise modulation of neovascularization; however, the structural complexity of PGs/GAGs obscures their mechanistic roles in vascular remodeling. This review systematically analyzes the regulatory roles of PGs/GAGs in the distinct phases of angiogenesis and vasculogenesis, which are two fundamental neovascularization processes. Additionally, we explored the emerging applications of PGs/GAGs in vascularized tissue engineering and regenerative medicine (VTERM), focusing on PG/GAG-functionalized biomaterials designed to mimic the native extracellular microenvironment and enhance specific signaling. This article critically evaluates the latest advances in optimizing these composite materials, and highlights the challenges associated with achieving spatiotemporal control over vascularization. By integrating profound molecular insights into innovative translational practices, this study establishes a theoretical framework for leveraging PGs/GAGs as multifunctional regulators in next-generation VTERM strategies.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"28 3","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482907","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}

{"title":"Endothelial GTPBP3 directs developmental angiogenesis and neovascularization after limb ischemia via the mtROS/HRl/ATF4/mTORC1 axis","authors":"Donglu Qin,&nbsp;Jiarui Hu,&nbsp;Yang Yang,&nbsp;Xin Li,&nbsp;Jia He,&nbsp;Jin Chen,&nbsp;Xin Guo,&nbsp;Cheng Wei,&nbsp;Fengjiao Wang,&nbsp;Ting Yi,&nbsp;Chenyu Li,&nbsp;Bilian Yu","doi":"10.1007/s10456-025-09994-4","DOIUrl":"10.1007/s10456-025-09994-4","url":null,"abstract":"<div><p>GTP binding protein 3 (GTPBP3) is a highly conserved enzyme involved in tRNA modification, is essential for 5-taurinomethyluridine (τm⁵U) biosynthesis, and is linked to mitochondrial dysfunction within cells. However, the specific roles of GTPBP3 in different cell types during vascular development and angiogenesis are not well understood. In this study, we assess the physiological functions of GTPBP3 in endothelial cells (ECs) using two conditional knockout mouse models. GTPBP3 deletion, specifically in ECs, resulted in embryonic lethality owing to irregularities in angiogenesis and vascular formation. Tamoxifen-inducible EC-specific GTPBP3 knockout (<i>Gtpbp3</i>^<i>iΔEC</i>) mice show reduced retinal sprouting angiogenesis and impaired neovascularization after limb ischemia. Mechanistically, GTPBP3 absence in ECs leads to mitochondrial dysfunction and an increase in mitochondrial reactive oxygen species (mtROS), which alters Heme-regulated eIF2α kinase (HRI)—activating transcription factor 4 (ATF4)—Sestrin2 pathway expression, inhibiting activation of the mTORC1 pathway and angiogenesis. However, treatment with MitoQ—an mtROS scavenger—improves angiogenic dysfunction. These results highlight GTPBP3 as a vital element for developmental angiogenesis and neovascularization after limb ischemia.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"28 3","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324320","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}