Angiogenesis最新文献

{"title":"Pathogenesis and molecular mechanisms of mutant TIE2-driven venous malformation","authors":"Lindsay J. Bischoff,&nbsp;Elisa Boscolo","doi":"10.1007/s10456-026-10088-y","DOIUrl":"10.1007/s10456-026-10088-y","url":null,"abstract":"<div><p>Venous malformation (VM) is the most common subtype of vascular malformation. Due to the chronic nature of this disorder, VM patients face significant morbidity and complications throughout their lives. Current therapeutic options can be limited, but recent advances in understanding the cellular and molecular mechanisms that underly VM pathogenesis provide hope for the discovery of more effective targeted therapies. These advances arise from a greater understanding of the cellular effects of VM-causative mutations, which has been aided by the development of more advanced and physiologically relevant model systems. In this review, we begin by providing a brief overview of the clinical characteristics and genetic driver mutations of the most common subtypes of all vascular anomalies (including vascular tumors and vascular malformations), providing context for our more detailed discussion of these aspects of VM. We further summarize the current treatment options available for VM patients and the advancements that have been made in the use of targeted therapies for these patients. We further discuss recent advances in the development of model systems that can be used to study VM pathogenesis. Finally, we focus this review on the mechanisms that are downstream of mutant TIE2, discussing structural features of the receptor, TIE2 signaling pathways, and its roles in vascular physiology and VM pathology.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 4","pages":""},"PeriodicalIF":11.2,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-026-10088-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148783167","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":"Integrin inhibition differentially remodels vascular networks in lung metastases driven by vessel co-option or angiogenesis","authors":"Laura Marcos-Zazo,&nbsp;Iván Carrera-Aguado,&nbsp;Jesús Gómez-Escudero,&nbsp;Patricia Berlana-Galán,&nbsp;Irene Torre-Cea,&nbsp;Elena Guerra-Paes,&nbsp;Celia Redondo-Gonzalez,&nbsp;Juan Sánchez-Mateos,&nbsp;Daniel Cáceres-Calle,&nbsp;Óscar Maiques,&nbsp;Miguel Pericacho,&nbsp;Susana Fraile,&nbsp;Telmo Rodrigues-Teixeira,&nbsp;Carmen García-Macías,&nbsp;Omar García-Sánchez,&nbsp;Lorena Benito-Garzón,&nbsp;Fernando Sánchez-Juanes,&nbsp;José M. Muñoz-Félix","doi":"10.1007/s10456-026-10085-1","DOIUrl":"10.1007/s10456-026-10085-1","url":null,"abstract":"<div><p>Tumor progression depends on an adequate blood supply to sustain oxygen and nutrients delivery. While tumor angiogenesis involves the formation of new blood vessels from pre-existing ones, vessel co-option represents a non-angiogenic vascularization strategy whereby tumor cells utilize pre-existing host vessels. Co-opted vessels have been considered refractory to anti-angiogenic therapies, and pharmacological modulation of co-opted vessels remains limited. In this study, we investigate the effects of low-dose cilengitide on tumor vascular remodeling in vessel co-option and angiogenic metastatic models. Our results reveal that cilengitide exerts distinct vascular effects depending on the mode of tumor vascularization. In vessel co-option-driven tumors, cilengitide treatment is associated with the remodeling of the co-opted vasculature into a more organized normalized vascular network, characterized by an increased number of functional blood vessels and enhanced vascular barrier integrity. In contrast, in angiogenic-driven tumors, cilengitide treatment promotes an expansion of the vascular network consistent with augmented, but structurally immature angiogenesis. Importantly, vascular remodeling in vessel co-option metastases is accompanied by enhanced blood vessel perfusion and reduced hypoxia, which correlates with enhanced responsiveness to chemotherapy. Conversely, in angiogenic metastases, the vascular network induced by low-dose cilengitide fails to support immunocompetent microenvironmental features and is associated with increased chemotherapy resistance. This study provides the first evidence that co-opted vasculature can be therapeutically targeted via integrin inhibition, suggesting vascular normalization remodeling as a potential strategy to overcome resistance in tumors undergoing vessel co-option.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 4","pages":""},"PeriodicalIF":11.2,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-026-10085-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148783166","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":"Antisense oligonucleotide-mediated disruption of mRNA localisation inhibits angiogenesis","authors":"Josy Augustine,&nbsp;Precious O. Owuamalam,&nbsp;Jennifer Nicell,&nbsp;Peter Barabas,&nbsp;Susanta Chatterjee,&nbsp;Michael O’Hare,&nbsp;Tim M. Curtis,&nbsp;Guilherme Costa","doi":"10.1007/s10456-026-10087-z","DOIUrl":"10.1007/s10456-026-10087-z","url":null,"abstract":"<div><p>mRNA localisation is a critical posttranscriptional mechanism that confers a spatiotemporal dimension to the control of gene expression. Among diverse outcomes, this process can result in compartmentalised protein synthesis and consequently, elicit localised cellular responses. Targeting mRNAs to their destination is often determined by localisation elements (LEs) contained in untranslated regions within targeted transcripts. Although mRNA localisation has been widely explored in the context of subcellular biology, its roles in tissue function are only just beginning to emerge. A defined set of transcripts accumulate at the leading edge of endothelial tip cells that guide emerging vessels during sprouting angiogenesis. This includes <i>RAB13</i> and <i>NET1</i> mRNAs, which encode proteins implicated in cytoskeletal remodelling processes underpinning cell motility. In this study, we tested the anti-angiogenic potential of antisense oligonucleotide (ASO)-based strategies designed to perturb <i>RAB13</i> and <i>NET1</i> localisation. Upon confirming that ASOs targeting LEs mislocalise these mRNAs without altering steady-state levels of the encoded proteins, we applied them to a series of in vitro, ex vivo and in vivo angiogenesis assays. Remarkably, the mislocalisation of <i>RAB13</i> and <i>NET1</i> inhibits chemotaxis and vessel sprouting in response to pro-angiogenic stimuli. Furthermore, vessel sprouting from mouse choroidal explants and retinal angiogenesis are also hindered by mRNA mislocalisation. Altogether, our strategy for disrupting spatial control of gene expression in endothelial cells opens new mechanistic avenues for the manipulation of vessel formation.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 4","pages":""},"PeriodicalIF":11.2,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-026-10087-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148782784","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":"A high-sensitivity TIE2–GRB2 BRET platform for functional and pharmacologic profiling of pathogenic variants associated with venous malformations","authors":"Hitomi Matsutani,&nbsp;Atsuro Oishi,&nbsp;Takuya Izumi-Tamura,&nbsp;Yumiko Hayashi,&nbsp;Masakazu Kurita,&nbsp;Tomoya Muto,&nbsp;Akihide Yoshimi,&nbsp;Hitoshi Ueno,&nbsp;Tomohiro Shiraishi,&nbsp;Kiyonori Harii,&nbsp;Akihiko Takushima,&nbsp;Hiroyasu Kidoya,&nbsp;Mine Ozaki","doi":"10.1007/s10456-026-10071-7","DOIUrl":"10.1007/s10456-026-10071-7","url":null,"abstract":"<div><p>TIE2 is an endothelial receptor tyrosine kinase (RTK) essential for vascular integrity, and constitutively active TIE2 mutants are involved in venous malformations (VMs). VMs are currently treated by surgery or sclerotherapy, but effective pharmacologic options remain limited, especially for surgically challenging Blue Rubber Bleb Nevus Syndrome (BRBNS). TIE2 activation has typically been assessed by immunoblotting of phosphoproteins, yet scalable assays applicable to pharmacological evaluation are still lacking. Here, we present a bioluminescence resonance energy transfer (BRET) biosensor that quantifies receptor-proximal TIE2 activation by monitoring recruitment of GRB2, a major adaptor in RTK signaling. This BRET sensor detects angiopoietin-1 (ANG-1) at physiological plasma concentrations and is compatible with a high-throughput format. Furthermore, it captures constitutive activity of TIE2 mutants associated with VMs and enables pharmacological evaluation of TIE2 variants. Notably, the T1105N–T1106P variant, frequently observed in BRBNS, exhibited relatively higher sensitivity to the clinical oncology drugs regorafenib and lenvatinib. To validate selected BRET-defined pharmacological profiles in an endothelial context, we used HUVEC-derived HUEhT-2 cells and established endothelial TIE2–GRB2 BRET measurements, followed by downstream AKT/ERK signaling analysis and tube formation assays. These endothelial assays largely supported the selected HEK293T BRET findings, particularly the pharmacological profile of T1105N–T1106P mutant, at receptor-proximal, downstream signaling, and functional levels. Together, this BRET-based biosensor establishes a two-step framework: HEK293T BRET enables efficient primary profiling, whereas endothelial assays provide orthogonal validation to support biological interpretation. This framework offers a practical strategy for prioritizing pharmacological candidates for further endothelial and in vivo validation toward therapeutic development.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 4","pages":""},"PeriodicalIF":11.2,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148752018","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":"Smad3 deficiency attenuates disease severity in a zebrafish model for Smad6-related aortic disease","authors":"Michiel Vanhooydonck,&nbsp;Maxim Verlee,&nbsp;Marta Santana Silva,&nbsp;Lore Pottie,&nbsp;Annekatrien Boel,&nbsp;Matthias Van Impe,&nbsp;Hanna De Saffel,&nbsp;Lisa Caboor,&nbsp;Anne Bonnin,&nbsp;Patrick Segers,&nbsp;Adelbert De Clercq,&nbsp;Yannick Gansemans,&nbsp;Filip Van Nieuwerburgh,&nbsp;Delfien Syx,&nbsp;Andy Willaert,&nbsp;Patrick Sips,&nbsp;Bert Callewaert","doi":"10.1007/s10456-026-10051-x","DOIUrl":"10.1007/s10456-026-10051-x","url":null,"abstract":"<div><p>Thoracic aortic dissection (TAD) associates with a high mortality rate. Treatment options are limited and mainly consist of surgical repair at critical aortic diameters as current pharmacological interventions are unable to stop disease progression. Despite the existence of different mouse models for thoracic aortic aneurysm (TAA) and TAD, the underlying disease mechanisms remain elusive. In humans, loss-of-function of <i>SMAD3</i> or <i>SMAD6</i> increases the risk for TAA. We therefore targeted both ohnologs of <i>smad3</i> and <i>smad6</i> in zebrafish in order to further investigate their contribution to aortic homeostasis. We found an increased diameter of the ventral aorta in <i>smad3a</i>^−/−;<i>smad3b</i>^−/− double knockout (<i>smad3a/b</i> DKO) zebrafish larvae, while <i>smad6a</i>^−/−;<i>smad6b</i>^−/− (<i>smad6a/b</i> DKO) zebrafish larvae have a reduced aortic diameter. <i>Smad3a/b</i> DKO survive normally to adulthood, but <i>smad6a/b</i> DKO die before the age of 8 months due to dissections and ruptures in the ventral aorta. <i>Smad6a/b</i> DKO zebrafish also show hypoplasia of the aortic arches and the distal part of the ventral aorta. Surprisingly, the <i>smad3a</i>^−/−;<i>smad3b</i>^−/−;<i>smad6a</i>^−/−;<i>smad6b</i>^−/− quadruple knockout (qKO) zebrafish model has normal survival and a milder vascular phenotype compared to the <i>smad6a/b</i> DKO. RNA sequencing of zebrafish larvae indicates upregulation of pathways related to melanogenesis, ribosome, blood vessel development and carboxylic acid transport, and downregulation of negative regulation of endopeptidase activity and immune system. Transcriptomic data of damaged aorta compared with healthy control aorta identifies significant differences in oxidative phosphorylation, mitochondrial function, extracellular matrix and the citrate cycle. In conclusion, data from our novel zebrafish models of thoracic aortic dissection and rupture indicate that SMAD3 function has an important modifying effect on the severe aortic manifestations induced by loss of SMAD6.</p><h3>Graphical abstract</h3><p>Legend “TAA” thoracic aortic aneurysm, “TAD” thoracic aortic dissection, “BAV” bicuspid aortic valve, “LOF” loss-of-function. Figure created with BioRender.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 4","pages":""},"PeriodicalIF":11.2,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722487","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":"Lysosomal channel TPC2 modulates microglia-endothelial signaling in choroidal angiogenesis","authors":"Yi Lu,&nbsp;Alice Reschigna,&nbsp;Franz Kynast,&nbsp;Zhuo Yang,&nbsp;Maximillian Gerhardt,&nbsp;Pavel Kielkowski,&nbsp;Siegfried Priglinger,&nbsp;Martin Biel,&nbsp;Stylianos Michalakis","doi":"10.1007/s10456-026-10082-4","DOIUrl":"10.1007/s10456-026-10082-4","url":null,"abstract":"<div><p>Pathological choroidal neovascularization underlies vision loss in neovascular age-related macular degeneration (nAMD), yet the molecular regulators coordinating vascular and immune components remain incompletely defined. Here, we investigated the role of the endolysosomal cation channel, two-pore channel 2 (TPC2) in choroidal angiogenesis. Loss of TPC2 in mice markedly reduced ex vivo choroidal sprouting, while pharmacological activation enhanced vascular growth. Mechanistically, <i>Tpc2</i>-deficiency led to downregulation of multiple microglia-derived pro-angiogenic factors and impaired the ability of the microglial secretome to stimulate neovascularization. In choroidal vascular cells, TPC2 loss attenuated NF-κB/MAPK signaling pathways. <i>Tpc2</i>-deficiency is also associated with lysosomal secretion of cathepsins, especially CTSD, resulting in decreased extracellular proteolytic activity and impaired paracrine regulation of angiogenesis. Extending these findings to human cells, <i>TPC2</i> knockout in iPSC-derived endothelial cells impaired migration, tube formation, and CTSD activity in the secretome, mirroring the murine phenotype. Together, these results establish TPC2 as one of the regulators of lysosome-mediated choroidal angiogenesis, highlighting its potential as a therapeutic target in nAMD.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 4","pages":""},"PeriodicalIF":11.2,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-026-10082-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720530","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":"3D co-culture model of tumor spheroid and endothelial cells unveils ccRCC aberrant vasculature and distinct sensitivity to targeted treatments","authors":"Noémie Brassard-Jollive,&nbsp;Yoann Atlas,&nbsp;Camille L. M. Compère,&nbsp;Corinne Ardidie-Robouant,&nbsp;Philippe Mailly,&nbsp;Morad El Bouchtaoui,&nbsp;Virginie Lelarge,&nbsp;Guillaume Blot,&nbsp;Nathalie Josseaume,&nbsp;Stéphanie De Oliveira,&nbsp;Christophe Helary,&nbsp;Christophe Leboeuf,&nbsp;Isabelle Cremer,&nbsp;Mathilde Sibony,&nbsp;Guilhem Bousquet,&nbsp;Stéphane Germain,&nbsp;Laurent Muller,&nbsp;Catherine Monnot","doi":"10.1007/s10456-026-10073-5","DOIUrl":"10.1007/s10456-026-10073-5","url":null,"abstract":"<div><p>Clear cell renal cell carcinoma (ccRCC), the most common renal cancer, is largely driven by von Hippel Lindau (VHL) protein deficiency. VHL inactivation promotes epithelial-to-mesenchymal transition (EMT), invasion, and hypervascularization, through vascular endothelial growth factor (VEGF) signaling, resulting in an abnormally complex vasculature. Given the limited prognostic value of microvessel density and the frequent development of resistance to VEGF-targeted therapies, the architecture of the ccRCC vascular network is likely a critical, underexplored determinant of therapeutic response. This study investigates the three-dimensional (3D) architecture of ccRCC vasculature within the tumor microenvironment and its response to drugs. Examination of human ccRCC samples revealed two vascular structures, designated ponds and sheets, that are morphologically distinct from tumor capillaries. High-resolution 3D imaging of optically cleared patient-derived xenografts revealed that ponds formed large, irregular structures with wide luminal cavity, whereas sheets were thin, elongated, and collapsed. We engineered a 3D in vitro tumor spheroid-endothelial cell co-culture model, incorporating EMT-like tumor spheroids co-cultured with endothelial cells, that mimicked pond architecture. Time-lapse imaging revealed a temporal link between tumor invasion and pond morphogenesis. Drug testing demonstrated that temsirolimus, crizotinib, and sunitinib impaired capillary morphogenesis and tumor invasion to varying extents in monoculture, while co-culture model reduced overall drug efficacy. Importantly, ponds exhibited markedly reduced sensitivity to sunitinib compared with adjacent capillaries, suggesting that they may contribute to anti-angiogenic resistance. This study defines key features and heterogeneity of ccRCC vascular architecture and highlights ponds as candidate contributors to treatment failure and targets for future interventions.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 4","pages":""},"PeriodicalIF":11.2,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688546","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":"Long-term angiogenic and thromboinflammatory signatures in post-COVID-19 syndrome","authors":"Arlette Araceli Mora Zetina,&nbsp;Erika Fabiola Ortega Sanchez,&nbsp;Brenda Saraí Zuñiga Ascencio,&nbsp;Armando Roberto Castorena Maldonado,&nbsp;Víctor Hugo Ahumada Topete,&nbsp;Luz María Torres Espíndola,&nbsp;Arnoldo Aquino Gálvez,&nbsp;Rosario Fernández Plata,&nbsp;Anjarath Lorena Higuera Iglesias,&nbsp;David Martínez Briseño,&nbsp;Aranza Bernal Silva,&nbsp;Misael Osmar García Martín,&nbsp;José Eduardo Márquez García,&nbsp;Angelica Moncada Morales,&nbsp;Jaime Chávez Alderete,&nbsp;Rafael Hernandez Zenteno,&nbsp;Eduardo Becerril Vargas,&nbsp;Daniela Josefina Cataneo Piña,&nbsp;José Leopoldo Aguilar Faisal,&nbsp;Jazmín García Machorro,&nbsp;Pedro López Sánchez,&nbsp;María Elena Hernandez Campos,&nbsp;Manuel Castillejos López","doi":"10.1007/s10456-026-10075-3","DOIUrl":"10.1007/s10456-026-10075-3","url":null,"abstract":"<div><h3>Background</h3><p>Post-COVID-19 syndrome is a major long-term sequela of severe SARS-CoV-2 infection, potentially involving persistent angiogenic and thromboinflammatory dysfunction, though long-term biomarker behavior remains unclear.</p><h3>Objective</h3><p>To evaluate the evolution of angiogenic and thromboinflammatory biomarkers in post-COVID-19 syndrome patients.</p><h3>Methods</h3><p>This ambispective cohort study was conducted at the National Institute of Respiratory Diseases in Mexico City. Thirty-two adults hospitalized for severe or critical COVID-19 in 2020 were followed for three and a half years. Paired plasma samples were collected during hospitalization and at long-term follow-up. Endothelial dysfunction markers included soluble P-selectin, vascular endothelial growth factor receptor 2, vascular endothelial growth factor D, and angiopoietin-1. Hemostasis was assessed by prothrombin time. Acute-phase proteins alpha-2-macroglobulin and haptoglobin were measured via immunoassay. Persistent symptoms were documented at follow-up.</p><h3>Results</h3><p>At three and a half years, persistent symptoms were common: fatigue in sixty-five point 6%, dyspnea in sixty-two point 5%, and concentration difficulties in sixty-five point 6%. Vascular endothelial growth factor D and angiopoietin-1 remained elevated. Alpha-2-macroglobulin stayed high, and prothrombin time was prolonged in a subset of patients.</p><h3>Conclusions</h3><p>Severe COVID-19 survivors show sustained angiogenic dysregulation and thromboinflammatory imbalance. Elevated vascular endothelial growth factor D and angiopoietin-1 indicate ongoing angiogenic perturbations, while increased alpha-2-macroglobulin and prolonged prothrombin time reflect persistent coagulation disturbances. These biomarkers may help identify long-term vascular alterations in post-COVID-19 syndrome.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 4","pages":""},"PeriodicalIF":11.2,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688615","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":"Semi-automated quantification of total and avascular retinal area in the rat model of oxygen-induced retinopathy","authors":"Husaam Qureishy,&nbsp;Amelia Morikuni,&nbsp;Michael D. Evans,&nbsp;Rehan Krishnan,&nbsp;Ellen C. Ingolfsland","doi":"10.1007/s10456-026-10070-8","DOIUrl":"10.1007/s10456-026-10070-8","url":null,"abstract":"<div><p>Quantification of retinal and avascular areas in the rat oxygen induced retinopathy (OIR) model is traditionally performed using time-intensive manual methods that may be subject to inter-rater variability. We developed and validated two open-source, semi-automated Fiji (Fiji is Just ImageJ) macros to measure total retinal area (RA) and avascular area (AA) in rat 50/10 OIR retinal flat mounts. Concordance correlation coefficients demonstrated high agreement between macro-derived and manual measurements for RA (0.988), AA (0.985), and AA/RA (0.983), with minimal bias observed. While inter-user variability was higher for macro-based AA measurements compared to manual methods, averaging results from two users improved precision. These semi-automated tools reduce analysis time and training burden while maintaining strong agreement with gold standard measurements. Although limited by user input requirements and single-laboratory validation, these macros provide accessible, standardized methods for retinal quantification and have the potential to improve reproducibility and efficiency in OIR research.</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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148652309","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":"Functional definition of endothelial progenitors by PROCR and PDGFRA co-expression","authors":"Cassandra Styke,&nbsp;Simranpreet Kaur,&nbsp;Seen-Ling Sim,&nbsp;Jilai Zhao,&nbsp;Chenhao Zhou,&nbsp;Ho Yi Wong,&nbsp;Jatin Patel,&nbsp;Edwige Roy,&nbsp;Mervyn C. Yoder,&nbsp;Richard P. Harvey,&nbsp;Abbas Shafiee,&nbsp;Kiarash Khosrotehrani","doi":"10.1007/s10456-026-10078-0","DOIUrl":"10.1007/s10456-026-10078-0","url":null,"abstract":"<div><p>The functional and molecular definition of progenitors giving rise to blood vessel endothelium in vivo remains disputed. Upon investigating the overlap of seemingly divergent reports currently defining putative endothelial progenitor cells (EPCs) using single-cell RNA-sequencing and flow cytometry, Protein C Receptor (PROCR) and Platelet-Derived Growth Factor Receptor Alpha (PDGFRA) largely overlapped with previously characterized murine aorta’s CD34⁺CD31^low endovascular progenitors (EVPs). Functional assays and lineage tracing in homeostatic aorta and excisional wounds demonstrated increased clonogenic capacity, engraftment potential, and ability to form differentiated endothelial (D) cells of PROCR⁺ PDGFRA⁺ EPCs, termed as refined endothelial progenitor cell (rEPC), as compared to PROCR^negPDGFRA^neg EVPs. Similar <i>PROCR</i> and <i>PDGFRA</i> expression in normal human aorta, and increased clonogenic capacity of CD34⁺CD31^lowPROCR⁺ endothelial cells from freshly isolated human term placenta were observed as compared to controls. Functional validation of human rEPCs is supported by PROCR enrichment, while PDGFRA co‑expression in human endothelial progenitor–like cells is supported at the transcriptomic level only. Thus, overlapping PROCR and PDGFRA expression in EVPs narrows the population with true functional progenitor capacity.</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/s10456-026-10078-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148652310","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}