Angiogenesis最新文献

{"title":"Vascular mimicry in zebrafish fin regeneration: how macrophages build new blood vessels","authors":"Anita Senk,&nbsp;Jennifer Fazzari,&nbsp;Valentin Djonov","doi":"10.1007/s10456-024-09914-y","DOIUrl":"10.1007/s10456-024-09914-y","url":null,"abstract":"<div><p>Vascular mimicry has been thoroughly investigated in tumor angiogenesis. In this study, we demonstrate for the first time that a process closely resembling tumor vascular mimicry is present during physiological blood vessel formation in tissue regeneration using the zebrafish fin regeneration assay. At the fin-regenerating front, vasculature is formed by mosaic blood vessels with endothelial-like cells possessing the morphological phenotype of a macrophage and co-expressing both endothelial and macrophage markers within single cells. Our data demonstrate that the vascular segments of the regenerating tissue expand, in part, through the transformation of adjacent macrophages into endothelial-like cells, forming functional, perfused channels and contributing to the de novo formation of microvasculature. Inhibiting the formation of tubular vascular-like structures by CVM-1118 prevents vascular mimicry and network formation resulting in a 70% shorter regeneration area with 60% reduced vessel growth and a complete absence of any signs of regeneration in half of the fin area. Additionally, this is associated with a significant reduction in macrophages. Furthermore, depleting macrophages using macrophage inhibitor PLX-3397, results in impaired tissue regeneration and blood vessel formation, namely a reduction in the regeneration area and vessel network by 75% in comparison to controls.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 3","pages":"397 - 410"},"PeriodicalIF":9.2,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140317713","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":"Connective tissue disorders in COVID-19: Reply to “People with a connective tissue disorder may be especially vulnerable to the endothelial damage that characterizes long COVID due to the fragility of their vasculature and slow wound healing”","authors":"Xiaoming Wu,&nbsp;Valerie A. Novakovic,&nbsp;Jialan Shi","doi":"10.1007/s10456-024-09915-x","DOIUrl":"10.1007/s10456-024-09915-x","url":null,"abstract":"<div><p>Connective tissue serves as a framework for other tissues and organs, supporting their functions, shielding them from harmful factors, and aiding repair. In COVID-19, damaged endothelial cells (ECs), increased endothelial permeability, and thrombi contribute to the connective tissue disorders. Even post-recovery, the damage to ECs and connective tissues persists, resulting in long COVID. Individuals with connective tissue disorders are prone to developing severe COVID-19 and experiencing long COVID symptoms. It is advised that these patients receive at least three vaccine doses, undergo early prophylactic antithrombotic therapy during acute COVID-19, and maintain prophylactic anticoagulant treatment in cases of long COVID.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 2","pages":"125 - 127"},"PeriodicalIF":9.2,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140292552","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":"Granzyme B degrades extracellular matrix and promotes inflammation and choroidal neovascularization","authors":"Gideon Obasanmi,&nbsp;Manjosh Uppal,&nbsp;Jing Z. Cui,&nbsp;Jeanne Xi,&nbsp;Myeong Jin Ju,&nbsp;Jun Song,&nbsp;Eleanor To,&nbsp;Siqi Li,&nbsp;Wania Khan,&nbsp;Darian Cheng,&nbsp;John Zhu,&nbsp;Lyden Irani,&nbsp;Isa Samad,&nbsp;Julie Zhu,&nbsp;Hyung-Suk Yoo,&nbsp;Alexandre Aubert,&nbsp;Jonathan Stoddard,&nbsp;Martha Neuringer,&nbsp;David J. Granville,&nbsp;Joanne A. Matsubara","doi":"10.1007/s10456-024-09909-9","DOIUrl":"10.1007/s10456-024-09909-9","url":null,"abstract":"<div><p>Age-related macular degeneration (AMD) is a common retinal neurodegenerative disease among the elderly. Neovascular AMD (nAMD), a leading cause of AMD-related blindness, involves choroidal neovascularization (CNV), which can be suppressed by anti-angiogenic treatments. However, current CNV treatments do not work in all nAMD patients. Here we investigate a novel target for AMD. Granzyme B (GzmB) is a serine protease that promotes aging, chronic inflammation and vascular permeability through the degradation of the extracellular matrix (ECM) and tight junctions. Extracellular GzmB is increased in retina pigment epithelium (RPE) and mast cells in the choroid of the healthy aging outer retina. It is further increased in donor eyes exhibiting features of nAMD and CNV. Here, we show in RPE-choroidal explant cultures that exogenous GzmB degrades the RPE-choroid ECM, promotes retinal/choroidal inflammation and angiogenesis while diminishing anti-angiogenic factor, thrombospondin-1 (TSP-1). The pharmacological inhibition of either GzmB or mast-cell degranulation significantly reduces choroidal angiogenesis. In line with our in vitro data, GzmB-deficiency reduces the extent of laser-induced CNV lesions and the age-related deterioration of electroretinogram (ERG) responses in mice. These findings suggest that targeting GzmB, a serine protease with no known endogenous inhibitors, may be a potential novel therapeutic approach to suppress CNV in nAMD.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 3","pages":"351 - 373"},"PeriodicalIF":9.2,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-024-09909-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140146628","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":"Photoreceptors inhibit pathological retinal angiogenesis through transcriptional regulation of Adam17 via c-Fos","authors":"Xudong Wang,&nbsp;Tianxi Wang,&nbsp;Satoshi Kaneko,&nbsp;Emil Kriukov,&nbsp;Enton Lam,&nbsp;Manon Szczepan,&nbsp;Jasmine Chen,&nbsp;Austin Gregg,&nbsp;Xingyan Wang,&nbsp;Angeles Fernandez-Gonzalez,&nbsp;S. Alex Mitsialis,&nbsp;Stella Kourembanas,&nbsp;Petr Baranov,&nbsp;Ye Sun","doi":"10.1007/s10456-024-09912-0","DOIUrl":"10.1007/s10456-024-09912-0","url":null,"abstract":"<div><p>Pathological retinal angiogenesis profoundly impacts visual function in vascular eye diseases, such as retinopathy of prematurity (ROP) in preterm infants and age-related macular degeneration in the elderly. While the involvement of photoreceptors in these diseases is recognized, the underlying mechanisms remain unclear. This study delved into the pivotal role of photoreceptors in regulating abnormal retinal blood vessel growth using an oxygen-induced retinopathy (OIR) mouse model through the c-Fos/A disintegrin and metalloprotease 17 (Adam17) axis. Our findings revealed a significant induction of c-Fos expression in rod photoreceptors, and c-Fos depletion in these cells inhibited pathological neovascularization and reduced blood vessel leakage in the OIR mouse model. Mechanistically, c-Fos directly regulated the transcription of <i>Adam17</i> a shedding protease responsible for the production of bioactive molecules involved in inflammation, angiogenesis, and cell adhesion and migration. Furthermore, we demonstrated the therapeutic potential by using an adeno-associated virus carrying a rod photoreceptor-specific short hairpin RNA against <i>c-fos</i> which effectively mitigated abnormal retinal blood vessel overgrowth, restored retinal thickness, and improved electroretinographic (ERG) responses. In conclusion, this study highlights the significance of photoreceptor c-Fos in ROP pathology, offering a novel perspective for the treatment of this disease.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 3","pages":"379 - 395"},"PeriodicalIF":9.2,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140130559","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":"Group XIV C-type lectins: emerging targets in tumor angiogenesis","authors":"Elliott J. Yee,&nbsp;Isaac Vigil,&nbsp;Yi Sun,&nbsp;Robert J. Torphy,&nbsp;Richard D. Schulick,&nbsp;Yuwen Zhu","doi":"10.1007/s10456-024-09907-x","DOIUrl":"10.1007/s10456-024-09907-x","url":null,"abstract":"<div><p>C-type lectins, distinguished by a C-type lectin binding domain (CTLD), are an evolutionarily conserved superfamily of glycoproteins that are implicated in a broad range of physiologic processes. The group XIV subfamily of CTLDs are comprised of CD93, CD248/endosialin, CLEC14a, and thrombomodulin/CD141, and have important roles in creating and maintaining blood vessels, organizing extracellular matrix, and balancing pro- and anti-coagulative processes. As such, dysregulation in the expression and downstream signaling pathways of these proteins often lead to clinically relevant pathology. Recently, group XIV CTLDs have been shown to play significant roles in cancer progression, namely tumor angiogenesis and metastatic dissemination. Interest in therapeutically targeting tumor vasculature is increasing and the search for novel angiogenic targets is ongoing. Group XIV CTLDs have emerged as key moderators of tumor angiogenesis and metastasis, thus offering substantial therapeutic promise for the clinic. Herein, we review our current knowledge of group XIV CTLDs, discuss each’s role in malignancy and associated potential therapeutic avenues, briefly discuss group XIV CTLDs in the context of two other relevant lectin families, and offer future direction in further elucidating mechanisms by which these proteins function and facilitate tumor growth.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 2","pages":"173 - 192"},"PeriodicalIF":9.2,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11021320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140100898","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":"Vascularized organoid-on-a-chip: design, imaging, and analysis","authors":"Tingting Yu,&nbsp;Qihang Yang,&nbsp;Bo Peng,&nbsp;Zhongze Gu,&nbsp;Dan Zhu","doi":"10.1007/s10456-024-09905-z","DOIUrl":"10.1007/s10456-024-09905-z","url":null,"abstract":"<div><p>Vascularized organoid-on-a-chip (VOoC) models achieve substance exchange in deep layers of organoids and provide a more physiologically relevant system in vitro. Common designs for VOoC primarily involve two categories: self-assembly of endothelial cells (ECs) to form microvessels and pre-patterned vessel lumens, both of which include the hydrogel region for EC growth and allow for controlled fluid perfusion on the chip. Characterizing the vasculature of VOoC often relies on high-resolution microscopic imaging. However, the high scattering of turbid tissues can limit optical imaging depth. To overcome this limitation, tissue optical clearing (TOC) techniques have emerged, allowing for 3D visualization of VOoC in conjunction with optical imaging techniques. The acquisition of large-scale imaging data, coupled with high-resolution imaging in whole-mount preparations, necessitates the development of highly efficient analysis methods. In this review, we provide an overview of the chip designs and culturing strategies employed for VOoC, as well as the applicable optical imaging and TOC methods. Furthermore, we summarize the vascular analysis techniques employed in VOoC, including deep learning. Finally, we discuss the existing challenges in VOoC and vascular analysis methods and provide an outlook for future development.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 2","pages":"147 - 172"},"PeriodicalIF":9.2,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139970722","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":"2-Desaza-annomontine (C81) impedes angiogenesis through reduced VEGFR2 expression derived from inhibition of CDC2-like kinases","authors":"T. J. Zech,&nbsp;A. Wolf,&nbsp;M. Hector,&nbsp;I. Bischoff-Kont,&nbsp;G. M. Krishnathas,&nbsp;S. Kuntschar,&nbsp;T. Schmid,&nbsp;F. Bracher,&nbsp;T. Langmann,&nbsp;R. Fürst","doi":"10.1007/s10456-024-09906-y","DOIUrl":"10.1007/s10456-024-09906-y","url":null,"abstract":"<div><p>Angiogenesis is a crucial process in the progression of various pathologies, like solid tumors, wet age-related macular degeneration, and chronic inflammation. Current anti-angiogenic treatments still have major drawbacks like limited efficacy in diseases that also rely on inflammation. Therefore, new anti-angiogenic approaches are sorely needed, and simultaneous inhibition of angiogenesis and inflammation is desirable. Here, we show that 2-desaza-annomontine (C81), a derivative of the plant alkaloid annomontine previously shown to inhibit endothelial inflammation, impedes angiogenesis by inhibiting CDC2-like kinases (CLKs) and WNT/<i>β</i>-catenin signaling. C81 reduced choroidal neovascularization in a laser-induced murine in vivo model, inhibited sprouting from vascular endothelial growth factor A (VEGF-A)-activated murine aortic rings ex vivo, and reduced angiogenesis-related activities of endothelial cells in multiple functional assays. This was largely phenocopied by CLK inhibitors and knockdowns, but not by inhibitors of the other known targets of C81. Mechanistically, CLK inhibition reduced VEGF receptor 2 (VEGFR2) mRNA and protein expression as well as downstream signaling. This was partly caused by a reduction of WNT/<i>β</i>-catenin pathway activity, as activating the pathway induced, while <i>β</i>-catenin knockdown impeded VEGFR2 expression. Surprisingly, alternative splicing of VEGFR2 was not detected. In summary, C81 and other CLK inhibitors could be promising compounds in the treatment of diseases that depend on angiogenesis and inflammation due to their impairment of both processes.</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":"27 2","pages":"245 - 272"},"PeriodicalIF":9.2,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-024-09906-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139968283","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":"Evidence of premature vascular dysfunction in young adults who regularly use e-cigarettes and the impact of usage length","authors":"Chloe Matheson,&nbsp;Tijana Simovic,&nbsp;Allison Heefner,&nbsp;Marisa Colon,&nbsp;Enrique Tunon,&nbsp;Kolton Cobb,&nbsp;Christopher Thode,&nbsp;Alison Breland,&nbsp;Caroline O. Cobb,&nbsp;Patrick Nana-Sinkam,&nbsp;Ryan Garten,&nbsp;Paula Rodriguez-Miguelez","doi":"10.1007/s10456-023-09903-7","DOIUrl":"10.1007/s10456-023-09903-7","url":null,"abstract":"<div><h3>Background</h3><p>Electronic (e-) cigarettes are increasingly popular tobacco products on the US market. Traditional tobacco products are known to cause vascular dysfunction, one of the earliest indicators of cardiovascular disease (CVD) development. However, little is known about the effect of regular e-cigarette use on vascular function. The purpose of this study was to investigate the impact of regular e-cigarette use on vascular function and cardiovascular health in young, healthy adults.</p><h3>Methods</h3><p>Twenty-one regular users of e-cigarettes (ECU) and twenty-one demographically matched non-users (NU) completed this study. Vascular health was assessed in the cutaneous microcirculation through different reactivity tests to evaluate overall functionality, endothelium-dependent vasodilation (EDD), and endothelium-independent vasodilation (EID). Macrovascular function was assessed using flow-mediated dilation (FMD).</p><h3>Results</h3><p>Our results suggest that regular users of e-cigarettes present with premature microvascular impairment when compared to non-users. Specifically, they exhibit lower hyperemic (<i>p</i> = 0.003), thermal (<i>p</i> = 0.010), and EDD (<i>p</i> = 0.004) responses. No differences in EID between the groups were identified. We also identified that individuals who use e-cigarettes for longer than 3 years also present with systemic manifestations, as observed by significantly reduced macrovascular (<i>p</i> = 0.002) and microvascular (<i>p</i> ≤ 0.044) function.</p><h3>Conclusions</h3><p>Our novel data suggests that young, apparently healthy, regular users of e-cigarettes present with premature vascular dysfunction in the microcirculation when compared to non-users. We have also identified systemic vascular dysfunction affecting both the micro and macrovasculature in those young individuals who used e-cigarettes for longer than 3 years. Taken together, these findings associate regular e-cigarette use with premature vascular dysfunctions and adverse cardiovascular outcomes.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 2","pages":"229 - 243"},"PeriodicalIF":9.2,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11021332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721292","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-resolution view of the heterogeneous aging endothelium","authors":"Sarah Dobner,&nbsp;Fanni Tóth,&nbsp;Laura P. M. H. de Rooij","doi":"10.1007/s10456-023-09904-6","DOIUrl":"10.1007/s10456-023-09904-6","url":null,"abstract":"<div><p>Vascular endothelial cell (EC) aging has a strong impact on tissue perfusion and overall cardiovascular health. While studies confined to the investigation of aging-associated vascular readouts in one or a few tissues have already drastically expanded our understanding of EC aging, single-cell omics and other high-resolution profiling technologies have started to illuminate the intricate molecular changes underlying endothelial aging across diverse tissues and vascular beds at scale. In this review, we provide an overview of recent insights into the heterogeneous adaptations of the aging vascular endothelium. We address critical questions regarding tissue-specific and universal responses of the endothelium to the aging process, EC turnover dynamics throughout lifespan, and the differential susceptibility of ECs to acquiring aging-associated traits. In doing so, we underscore the transformative potential of single-cell approaches in advancing our comprehension of endothelial aging, essential to foster the development of future innovative therapeutic strategies for aging-associated vascular conditions.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 2","pages":"129 - 145"},"PeriodicalIF":9.2,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11021252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139696827","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":"People with a connective tissue disorder may be especially vulnerable to the endothelial damage that characterizes long COVID due to the fragility of their vasculature and slow wound healing","authors":"Jeffrey Lubell","doi":"10.1007/s10456-024-09908-w","DOIUrl":"10.1007/s10456-024-09908-w","url":null,"abstract":"<div><p>A growing body of evidence documents the central role that endothelial damage plays in the pathophysiology of long COVID. But it remains unclear why only certain people get Long COVID and why recovery times are so long for many affected individuals. One potential explanation is that some forms of long COVID are experienced disproportionately by people with a connective tissue disorder who are more vulnerable than others to incurring serious damage to the endothelium and the vascular extracellular matrix from the inflammatory processes triggered by COVID-19 and much slower to heal. Further research is needed to explore this hypothesis.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 2","pages":"123 - 124"},"PeriodicalIF":9.2,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139690978","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}