Angiogenesis最新文献

{"title":"CreER activation transiently disrupts angiogenesis by reducing proliferation and promoting apoptosis in vascular endothelial cells","authors":"Elena Ioannou,&nbsp;Mengmeng Dong,&nbsp;Victoria S. Rashbrook,&nbsp;Christiana Ruhrberg,&nbsp;Martina Rudnicki","doi":"10.1007/s10456-026-10040-0","DOIUrl":"10.1007/s10456-026-10040-0","url":null,"abstract":"<div><p>Tamoxifen-inducible gene targeting in mice with estrogen receptor-dependent Cre (CreER) recombinase has enormously advanced vascular biology research. However, CreER activation under the control of vascular endothelial promoters causes off-target effects that impair the vascularization of the retina, a widely used model to study the molecular and cellular mechanisms of angiogenesis. Although ubiquitously expressed CreER is also used to study retinal angiogenesis, it remains unknown whether it causes similar or more severe off-target effects compared to endothelial-selective CreER activation. Moreover, the molecular and cellular processes disrupted by CreER activation in endothelial cells remain to be identified. Here, we demonstrate that ubiquitous CreER activation in postnatal mice decreases body growth and impairs retinal angiogenesis. We further show that CreER activation slows endothelial cell proliferation and promotes apoptosis concomitant with p21/CDKN1A upregulation in the angiogenic retina, although retinal vasculature progressively normalizes. By contrast, CreER activation in quiescent adult retinal vasculature did not induce endothelial cell apoptosis or p21 activation. Altogether, our findings indicate that ubiquitous promoters should be avoided to drive CreER expression when studying gene function during retinal angiogenesis, and that CreER activation controls, although essential to account for endothelial apoptosis and proliferation defects in short-term studies, may be less critical for adult vascular studies.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 3","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-026-10040-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829368","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 human endothelial and adipose stem cell-based co-culture model for venous malformations","authors":"Mohammadhassan Ansarizadeh,&nbsp;Bojana Lazovic,&nbsp;Zahra Sarmadian,&nbsp;Abhishek Singh,&nbsp;Ryan Hicks,&nbsp;Lauri Eklund","doi":"10.1007/s10456-026-10045-9","DOIUrl":"10.1007/s10456-026-10045-9","url":null,"abstract":"<div>\u0000 \u0000 <p>Venous malformations (VMs) are developmental defects in vascular morphogenesis characterized by enlarged vein-like channels and defective perivascular cell coverage. The majority of VMs are caused by somatic mutations in endothelial cell (EC) receptor tyrosine kinase TIE2, but current medicinal options are limited. The common bottleneck when testing new therapeutic strategies and identifying efficient drug candidates is the absence of a reliable and robust model for replicating the characteristics of VMs. We report here on an advanced in vitro model for recapitulating cellular and molecular pathologies of the VM-causative <i>TIE2</i>^L914F mutation by co-culturing human adipose tissue-derived stem cells (hASCs) with either human umbilical vein ECs (HUVECs) retrovirally transduced to express <i>TIE2</i>^L914F or with induced pluripotent stem cell-derived ECs (iECs) with locus-targeted <i>TIE2</i>^L914F. For comparison, cellular and molecular crosstalk between vascular cell types was investigated in HUVEC and primary vascular smooth muscle cell (vSMC) co-cultures. Advanced microscopy and transcriptomic analysis were used to investigate the cellular and molecular phenotypes in vascular cell types. Comparison of <i>TIE2</i>^WT, gain- (<i>TIE2</i>^L914F) and loss-of-function mutations (<i>TIE2</i>^KO) revealed the importance of TIE2 signaling for vascular network formation in hASC/EC co-cultures. The model recapitulated the cellular hallmarks of the VMs and revealed gene signatures and signaling pathways relevant to VM pathologies. The data also demonstrated the utility of the hASC/EC model as a screening platform for VM pharmacotherapies. Overall, this work establishes a versatile platform for studying disease mechanisms affecting the vasculature and provides new insights into VM pathobiology and screening potential for therapeutic applications targeting VMs.</p>\u0000 </div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 3","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-026-10045-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147802099","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":"Reconsidering the metabolic specificity of ACLY-dependent angiogenesis","authors":"Yan Zhang","doi":"10.1007/s10456-026-10047-7","DOIUrl":"10.1007/s10456-026-10047-7","url":null,"abstract":"","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 3","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147802087","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":"Neuropilin 1 (NRP1) conveys SEMA3A signals to restrict physiological angiogenesis","authors":"Marco Spreafico,&nbsp;Elena Guzzolino,&nbsp;Francesca Fanuele,&nbsp;Gaia Gestri,&nbsp;Carlotta Tacconi,&nbsp;Sara Palermo,&nbsp;Matilde Tricco,&nbsp;Valeria Catroppa,&nbsp;Ayazhan Aiypova,&nbsp;Laura Denti,&nbsp;Caroline Pellet-Many,&nbsp;Christiana Ruhrberg,&nbsp;Alessandro Fantin","doi":"10.1007/s10456-026-10033-z","DOIUrl":"10.1007/s10456-026-10033-z","url":null,"abstract":"<div>\u0000 \u0000 <p>The class 3 semaphorin SEMA3A is a secreted glycoprotein that serves as an evolutionary conserved axon repellent with proposed vascular functions. In mice, SEMA3A is dispensable for developmental brain, limb or trunk blood vessel patterning, but restricts vessel branching in the zebrafish embryo trunk. Whereas neuropilin 1 (NRP1) is thought to be the SEMA3A receptor in the mouse, prior reports identified Plexin D1 as the Sema3a receptor in zebrafish trunk vessel patterning, with previous knockdown and knockout studies yielding contradictory results on Nrp1 requirement for vessel patterning in zebrafish. To resolve these discrepancies, we have refined the prior knockdown strategy to limit off target effects and generated mutant zebrafish embryos lacking both Nrp1a and Nrp1b paralogues to show that Nrp1 restricts trunk vessel patterning in a Sema3a-dependent manner. In agreement, we found that NRP1 is required in human endothelial cells for SEMA3A-induced repulsion. Moreover, we show that SEMA3A action via NRP1 does not involve the splicing regulation of <i>FLT1</i>, previously proposed to act downstream of Plexin D1. Instead, sustained NRP1 activation independent of SEMA3A increases the expression of the anti-angiogenic soluble FLT1 (sFLT1), establishing a feedback mechanism to limit endothelial proliferation. Together, these findings demonstrate a dual role for NRP1 in shaping physiological vascular morphogenesis. Thus, NRP1 mediates repulsive SEMA3A cues in endothelial cells, in analogy to its role in axon guidance, and further restricts angiogenesis by promoting the release of sFLT1 in a SEMA3A-independent manner.</p>\u0000 </div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 3","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-026-10033-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147802100","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":"Platelet-derived growth factor receptor β F7 mutations result in and exacerbate the severity of vascular dysplasia in the brain arteriovenous malformation through enhancing angiogenesis","authors":"Alka Yadav,&nbsp;Leandro Barbosa Do Prado,&nbsp;Mustafa Mohamed,&nbsp;Calvin Wang,&nbsp;Joshua Shi,&nbsp;Zahra Shabani,&nbsp;Rich Liang,&nbsp;Kelly Press,&nbsp;Courtney Tom,&nbsp;Ethan A. Winkler,&nbsp;Hua Su","doi":"10.1007/s10456-026-10044-w","DOIUrl":"10.1007/s10456-026-10044-w","url":null,"abstract":"<div>\u0000 \u0000 <p>Brain arteriovenous malformations (bAVMs) are tangles of abnormal vessels that shunt blood directly from arteries to veins. The reduction of pericytes is linked to hemorrhage in bAVMs. The Pdgfb/Pdgfrβ signaling pathway is crucial for regulating pericyte recruitment during angiogenesis. Here, we show that mice with <i>Pdgfrβ</i> F7 mutations developed cerebrovascular dysplasia in the brain’s angiogenic region, associated with increased pro-angiogenic and inflammatory signaling. Interestingly, the expression of activin receptor-like kinase 1 (Alk1) is decreased in the brain’s angiogenic region of <i>Pdgfrβ</i> F7 heterozygous mice. Overexpression of ALK1 in brain endothelial cells (ECs) reduces angiogenic signaling and the severity of vascular dysplasia in <i>Pdgfrβ</i> F7 heterozygous mice. <i>Pdgfrβ</i> F7 mutations also increased dysplastic vessels and reduced pericyte coverage in the bAVM in endoglin-deficient mice. Endoglin is an AVM causative gene. Our data indicate that <i>Pdgfrβ</i> F7 mutations result in cerebrovascular dysplasia and worsen the bAVM phenotype in endoglin mutant mice by enhancing angiogenesis and inflammation. Overexpression of ALK1 in brain ECs reduces the severity of cerebrovascular dysplasia in <i>Pdgfrβ</i> F7 heterozygous mice through downregulating angiogenic signaling.</p>\u0000 </div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 3","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-026-10044-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147802097","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":"PINCH proteins as dual-function nodes in vascular mural cell homeostasis: from cytoplasmic scaffolds to nuclear gatekeepers","authors":"Bo Jiang,&nbsp;Hongjun Liu","doi":"10.1007/s10456-026-10043-x","DOIUrl":"10.1007/s10456-026-10043-x","url":null,"abstract":"<div>\u0000 \u0000 <p>Wang and colleagues recently reported that PINCH proteins maintain vascular mural cell homeostasis through integrated cytoplasmic signaling and nuclear transcriptional mechanisms, identifying PINCH1 as a direct transcriptional coregulator of genes involved in inflammation, differentiation, and neurovascular integrity. While their multi-omics approach provides compelling mechanistic insight, several critical questions remain that warrant further investigation. This commentary discusses four key areas for future exploration: (1) the regulation of PINCH nucleocytoplasmic shuttling by mechanical cues, which remains a testable hypothesis given the mechanosensitivity of related focal adhesion proteins; (2) the need to dissect the relative contributions of cytoplasmic versus nuclear PINCH functions using compartment-restricted mutants and inducible deletion systems, as constitutive knockout models limit interpretation; (3) the unresolved hierarchy between signaling dysregulation and transcriptional reprogramming, which currently reflects correlative rather than causal findings; and (4) the importance of functional validation in human cells and tissues to establish whether PINCH downregulation drives vascular pathology or represents a secondary event. Addressing these questions will be essential to fully understand PINCH biology and to assess its therapeutic potential in vascular diseases such as atherosclerosis and aortic aneurysm.</p>\u0000 </div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 3","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147802098","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":"Evolving biopsy strategies for molecular profiling of brain arteriovenous malformations","authors":"Zhenghong Peng,&nbsp;Li Zhang,&nbsp;Jiasen Ye,&nbsp;Zuoyue Duan,&nbsp;Tianqi Tu","doi":"10.1007/s10456-026-10041-z","DOIUrl":"10.1007/s10456-026-10041-z","url":null,"abstract":"<div><p>Brain arteriovenous malformations (BAVMs) are increasingly recognized as dynamic vascular diseases driven by endothelial genetic alterations and dysregulated signaling pathways, rather than as static structural anomalies. Accumulating evidence from both hereditary and sporadic forms of BAVMs has established endothelial signaling dysfunction as a central pathogenic mechanism underlying aberrant angiogenesis, progressive lesion remodeling, and vascular instability that predisposes to hemorrhage. These insights have fundamentally shifted the conceptual framework of BAVMs toward a pathway-driven disease model. Despite this progress, direct access to biologically informative molecular material from living AVM lesions remains limited, posing a major barrier to detailed mechanistic interrogation and the translation of molecular insights into clinical decision-making. Historically, molecular characterization of AVMs has relied almost exclusively on surgically resected tissue, restricting analyses to selected patient populations and frequently reflecting late-stage disease biology. Such approaches provide limited insight into disease initiation, temporal evolution, or treatment-induced molecular changes. Recent advances in minimally invasive biopsy strategies, particularly those leveraging endovascular access, have begun to overcome these limitations by enabling molecular interrogation of AVMs in vivo. In this mini review, we summarize emerging approaches for molecular profiling of AVMs, with a primary focus on BAVMs, while also drawing on relevant studies in extracranial and other arteriovenous malformations that share common endovascular access routes, technical principles, and translational implications.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 3","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147802096","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":"Correction: Endothelial LRRC8A mitigates pressure overload-induced cardiac hypertrophy by promoting coronary angiogenesis","authors":"Lingjun Jie,&nbsp;Baolong Feng,&nbsp;Yufan Zhou,&nbsp;Chan Du,&nbsp;Wenlin Zhou,&nbsp;Ruonan Zhang,&nbsp;Wei Shen,&nbsp;Jiajin Chen,&nbsp;Penglong Wu,&nbsp;Xu Kong,&nbsp;Yuliang Zhan,&nbsp;Meimei Shi,&nbsp;Guiyang Li,&nbsp;Lei Li,&nbsp;Lei Pan,&nbsp;Yanhui Zhang","doi":"10.1007/s10456-026-10035-x","DOIUrl":"10.1007/s10456-026-10035-x","url":null,"abstract":"","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 2","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147525393","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":"The vascular contribution to immunotherapy success","authors":"Arjan W. Griffioen,&nbsp;Judy R. van Beijnum,&nbsp;Sacha Jacobs,&nbsp;Mattie Cassee,&nbsp;Myra Castel,&nbsp;Patrycja Nowak-Sliwinska","doi":"10.1007/s10456-026-10036-w","DOIUrl":"10.1007/s10456-026-10036-w","url":null,"abstract":"<div>\u0000 \u0000 <p>Angiogenesis represents a mechanism enabling tumors to evade immune surveillance. This immune escape is mediated, at least in part, by angiogenic factor-induced endothelial cell anergy, which suppresses leukocyte adhesion and infiltration into the tumor microenvironment. Consequently, it is becoming increasingly evident that the efficacy of immunotherapy can be improved by its combination with anti-angiogenic agents. Numerous studies, including clinical trials, have provided proof of this concept. A paper in this issue of <i>Angiogenesis</i> further substantiates this paradigm by demonstrating that normalizing the tumor vasculature and overcoming endothelial cell anergy also ameliorates the activity of CAR T cell therapy. Here, we place these findings into a broader mechanistic context and discuss their implications for combination treatment strategies.</p>\u0000 </div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 2","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147441591","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":"Progressive endothelial coverage enhances hemocompatibility and prevents calcification in bioprosthetic valve tissue","authors":"Bastien Poitier,&nbsp;Ulysse Richez,&nbsp;Joseph Roux-de-Bezieux,&nbsp;Peter Ivak,&nbsp;Jeanne Rancic,&nbsp;Hugo Charrier,&nbsp;Christian Latremouille,&nbsp;Christophe Peronino,&nbsp;Jean Christian Roussel,&nbsp;Elisa Rossi,&nbsp;Salma El-Batti,&nbsp;Michel Kindo,&nbsp;Bruno Saubamea,&nbsp;Yuri Pya,&nbsp;Corinne Lesaffre,&nbsp;Antoine Capel,&nbsp;Paul Achouh,&nbsp;Ivan Netuka,&nbsp;David M. Smadja","doi":"10.1007/s10456-026-10039-7","DOIUrl":"10.1007/s10456-026-10039-7","url":null,"abstract":"<div><h3>Background</h3><p>Exploring the hemocompatibility of bioprosthetic heart valves (BHVs) has been challenging due to the scarcity of non-degenerated material.</p><h3>Objectives</h3><p>This study has two complementary objectives (1) To characterize the extent and temporal kinetics of endothelial coverage of BHVs implanted in humans; (2) To investigate, in a rat model, the impact of pericardial endothelialization on tissue calcification.</p><h3>Methods</h3><p>We employed histology and electron microscopy to assess cellular organization in non-degenerated BHVs and conducted hemodynamic simulations to evaluate shear stress fields in the ejection valves area. Furthermore, we investigated the impact of pericardium endothelial coverage on calcification using endothelial colony-forming cells (ECFCs) cultured on bovine pericardium discs implanted in athymic nude rats for 18 days. Calcium content was quantified through acetylene flame atomic absorption spectrophotometry.</p><h3>Results</h3><p>We observed inflammatory cell infiltration within all explanted BHVs, as well as fibrin deposit on top of the leaflets. Endothelial coverage emerged in long-term implants (&gt; 180 days) but remained incomplete in aortic valves, which could be linked to high shear stress levels in aortic position confirmed in hemodynamic simulations. Besides, the rat experiments revealed that the discs covered with fibrin + ECFCs were significantly less calcified than those covered with fibrin alone (respectively, median = 0.9 µg Ca/mg tissue; IQR: 0.7–1.1 vs median = 18.3 µg Ca/mg tissue; IQR: 9–34.9; p = 0.0003), and less extensively colonized by neutrophils.</p><h3>Conclusions</h3><p>Human explanted BHVs showed intact leaflets with a fibrin layer and organized endothelial coverage, without detectable calcification over the short observation period. In rats, endothelialization was associated with significantly reduced pericardial calcification, suggesting a potential protective effect. However, the limited follow-up in humans precludes conclusions on a causal role of endothelial coverage in hemocompatibility or protection against calcification.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 2","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147375844","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}