Angiogenesis最新文献

{"title":"CCL4 contributes to aging related angiogenic insufficiency through activating oxidative stress and endothelial inflammation","authors":"Ting-Ting Chang,&nbsp;Liang-Yu Lin,&nbsp;Ching Chen,&nbsp;Jaw-Wen Chen","doi":"10.1007/s10456-024-09922-y","DOIUrl":"10.1007/s10456-024-09922-y","url":null,"abstract":"<div><p>Aging is a natural process associated with chronic inflammation in the development of vascular dysfunction. We hypothesized that chemokine C-C motif ligands 4 (CCL4) might play a vital role in aging-related vascular dysfunction. Circulating CCL4 was up-regulated in elderly subjects and in aged animals. CCL4 inhibition reduced generation of reactive oxygen species (ROS), attenuated inflammation, and restored cell functions in endothelial progenitor cells from elderly subjects and in aged human aortic endothelial cells. CCL4 promoted cell aging, with impaired cell functioning, by activating ROS production and inflammation. CCL4 knockout mice and therapeutic administration of anti-CCL4 neutralizing antibodies exhibited vascular and dermal anti-aging effects, with improved wound healing, via the down-regulation of inflammatory proteins and the activation of angiogenic proteins. Altogether, our findings suggested that CCL4 may contribute to aging-related vascular dysfunction via activating oxidative stress and endothelial inflammation. CCL4 may be a potential therapeutic target for vascular protections during aging.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 3","pages":"475 - 499"},"PeriodicalIF":9.2,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140910872","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":"Distinct roles of SOX9 in self-renewal of progenitors and mesenchymal transition of the endothelium","authors":"Jilai Zhao,&nbsp;Laura Sormani,&nbsp;Sebastien Jacquelin,&nbsp;Haiming Li,&nbsp;Cassandra Styke,&nbsp;Chenhao Zhou,&nbsp;Jonathan Beesley,&nbsp;Linus Oon,&nbsp;Simranpreet Kaur,&nbsp;Seen-Ling Sim,&nbsp;Ho Yi Wong,&nbsp;James Dight,&nbsp;Ghazaleh Hashemi,&nbsp;Abbas Shafiee,&nbsp;Edwige Roy,&nbsp;Jatin Patel,&nbsp;Kiarash Khosrotehrani","doi":"10.1007/s10456-024-09927-7","DOIUrl":"10.1007/s10456-024-09927-7","url":null,"abstract":"<div><p>Regenerative capabilities of the endothelium rely on vessel-resident progenitors termed endothelial colony forming cells (ECFCs). This study aimed to investigate if these progenitors are impacted by conditions (i.e., obesity or atherosclerosis) characterized by increased serum levels of oxidized low-density lipoprotein (oxLDL), a known inducer of Endothelial-to-Mesenchymal Transition (EndMT). Our investigation focused on understanding the effects of EndMT on the self-renewal capabilities of progenitors and the associated molecular alterations. In the presence of oxLDL, ECFCs displayed classical features of EndMT, through reduced endothelial gene and protein expression, function as well as increased mesenchymal genes, contractility, and motility. Additionally, ECFCs displayed a dramatic loss in self-renewal capacity in the presence of oxLDL. RNA-sequencing analysis of ECFCs exposed to oxLDL validated gene expression changes suggesting EndMT and identified SOX9 as one of the highly differentially expressed genes. ATAC sequencing analysis identified SOX9 binding sites associated with regions of dynamic chromosome accessibility resulting from oxLDL exposure, further pointing to its importance. EndMT phenotype and gene expression changes induced by oxLDL in vitro or high fat diet (HFD) in vivo were reversed by the silencing of SOX9 in ECFCs or the endothelial-specific conditional knockout of Sox9 in murine models. Overall, our findings support that EndMT affects vessel-resident endothelial progenitor’s self-renewal. SOX9 activation is an early transcriptional event that drives the mesenchymal transition of endothelial progenitor cells. The identification of the molecular network driving EndMT in vessel-resident endothelial progenitors presents a new avenue in understanding and preventing a range of condition where this process is involved.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 3","pages":"545 - 560"},"PeriodicalIF":9.2,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908369","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":"Blood flow regulates acvrl1 transcription via ligand-dependent Alk1 activity","authors":"Anthony R. Anzell,&nbsp;Amy B. Kunz,&nbsp;James P. Donovan,&nbsp;Thanhlong G. Tran,&nbsp;Xinyan Lu,&nbsp;Sarah Young,&nbsp;Beth L. Roman","doi":"10.1007/s10456-024-09924-w","DOIUrl":"10.1007/s10456-024-09924-w","url":null,"abstract":"<div><p>Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by the development of arteriovenous malformations (AVMs) that can result in significant morbidity and mortality. HHT is caused primarily by mutations in bone morphogenetic protein receptors <i>ACVRL1</i>/ALK1, a signaling receptor, or endoglin (<i>ENG</i>), an accessory receptor. Because overexpression of <i>Acvrl1</i> prevents AVM development in both <i>Acvrl1</i> and <i>Eng</i> null mice, enhancing <i>ACVRL1</i> expression may be a promising approach to development of targeted therapies for HHT. Therefore, we sought to understand the molecular mechanism of <i>ACVRL1</i> regulation. We previously demonstrated in zebrafish embryos that <i>acvrl1</i> is predominantly expressed in arterial endothelial cells and that expression requires blood flow. Here, we document that flow dependence exhibits regional heterogeneity and that <i>acvrl1</i> expression is rapidly restored after reinitiation of flow. Furthermore, we find that <i>acvrl1</i> expression is significantly decreased in mutants that lack the circulating Alk1 ligand, Bmp10, and that, in the absence of flow, intravascular injection of BMP10 or the related ligand, BMP9, restores <i>acvrl1</i> expression in an Alk1-dependent manner. Using a transgenic <i>acvrl1:egfp</i> reporter line, we find that flow and Bmp10 regulate <i>acvrl1</i> at the level of transcription. Finally, we observe similar ALK1 ligand-dependent increases in <i>ACVRL1</i> in human endothelial cells subjected to shear stress. These data suggest that ligand-dependent Alk1 activity acts downstream of blood flow to maintain or enhance <i>acvrl1</i> expression via a positive feedback mechanism, and that ALK1 activating therapeutics may have dual functionality by increasing both ALK1 signaling flux and <i>ACVRL1</i> expression.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 3","pages":"501 - 522"},"PeriodicalIF":9.2,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896872","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":"IC100, a humanized therapeutic monoclonal anti-ASC antibody alleviates oxygen-induced retinopathy in mice","authors":"Huijun Yuan,&nbsp;Shaoyi Chen,&nbsp;Matthew R. Duncan,&nbsp;Juan Pablo de Rivero Vaccari,&nbsp;Robert W. Keane,&nbsp;W. Dalton Dietrich,&nbsp;Tsung-Han Chou,&nbsp;Merline Benny,&nbsp;Augusto F. Schmidt,&nbsp;Karen Young,&nbsp;Kevin K. Park,&nbsp;Vittorio Porciatti,&nbsp;M. Elizabeth Hartnett,&nbsp;Shu Wu","doi":"10.1007/s10456-024-09917-9","DOIUrl":"10.1007/s10456-024-09917-9","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Retinopathy of prematurity (ROP), which often presents with bronchopulmonary dysplasia (BPD), is among the most common morbidities affecting extremely premature infants and is a leading cause of severe vision impairment in children worldwide. Activations of the inflammasome cascade and microglia have been implicated in playing a role in the development of both ROP and BPD. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is pivotal in inflammasome assembly. Utilizing mouse models of both oxygen-induced retinopathy (OIR) and BPD, this study was designed to test the hypothesis that hyperoxia induces ASC speck formation, which leads to microglial activation and retinopathy, and that inhibition of ASC speck formation by a humanized monoclonal antibody, IC100, directed against ASC, will ameliorate microglial activation and abnormal retinal vascular formation.&lt;/p&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;We first tested ASC speck formation in the retina of ASC-citrine reporter mice expressing ASC fusion protein with a C-terminal citrine (fluorescent GFP isoform) using a BPD model that causes both lung and eye injury by exposing newborn mice to room air (RA) or 85% O&lt;sub&gt;2&lt;/sub&gt; from postnatal day (P) 1 to P14. The retinas were dissected on P14 and retinal flat mounts were used to detect vascular endothelium with AF-594-conjugated isolectin B4 (IB4) and citrine-tagged ASC specks. To assess the effects of IC100 on an OIR model, newborn ASC citrine reporter mice and wildtype mice (C57BL/6 J) were exposed to RA from P1 to P6, then 75% O&lt;sub&gt;2&lt;/sub&gt; from P7 to P11, and then to RA from P12 to P18. At P12 mice were randomized to the following groups: RA with placebo PBS (RA-PBS), O&lt;sub&gt;2&lt;/sub&gt; with PBS (O&lt;sub&gt;2&lt;/sub&gt;-PBS), O&lt;sub&gt;2&lt;/sub&gt; + IC100 intravitreal injection (O&lt;sub&gt;2&lt;/sub&gt;-IC100-IVT), and O&lt;sub&gt;2&lt;/sub&gt; + IC100 intraperitoneal injection (O&lt;sub&gt;2&lt;/sub&gt;-IC100-IP). Retinal vascularization was evaluated by flat mount staining with IB4. Microglial activation was detected by immunofluorescence staining for allograft inflammatory factor 1 (AIF-1) and CD206. Retinal structure was analyzed on H&amp;E-stained sections, and function was analyzed by pattern electroretinography (PERG). RNA-sequencing (RNA-seq) of the retinas was performed to determine the transcriptional effects of IC100 treatment in OIR.&lt;/p&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;ASC specks were significantly increased in the retinas by hyperoxia exposure and colocalized with the abnormal vasculature in both BPD and OIR models, and this was associated with increased microglial activation. Treatment with IC100-IVT or IC100-IP significantly reduced vaso-obliteration and intravitreal neovascularization. IC100-IVT treatment also reduced retinal microglial activation, restored retinal structure, and improved retinal function. RNA-seq showed that IC100 treatment corrected the induction of genes associated with angiogenesis, leukocyte migration, and VEGF signaling caused by O&lt;sub&gt;2&lt;/","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 3","pages":"423 - 440"},"PeriodicalIF":9.2,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856165","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":"Somatic BrafV600E mutation in the cerebral endothelium induces brain arteriovenous malformations","authors":"Tianqi Tu,&nbsp;Jiaxing Yu,&nbsp;Chendan Jiang,&nbsp;Shikun Zhang,&nbsp;Jingwei Li,&nbsp;Jian Ren,&nbsp;Shiju Zhang,&nbsp;Yuan Zhou,&nbsp;Ziwei Cui,&nbsp;Haohan Lu,&nbsp;Xiaosheng Meng,&nbsp;Zhanjing Wang,&nbsp;Dong Xing,&nbsp;Hongqi Zhang,&nbsp;Tao Hong","doi":"10.1007/s10456-024-09918-8","DOIUrl":"10.1007/s10456-024-09918-8","url":null,"abstract":"<div><p>Current treatments of brain arteriovenous malformation (BAVM) are associated with considerable risks and at times incomplete efficacy. Therefore, a clinically consistent animal model of BAVM is urgently needed to investigate its underlying biological mechanisms and develop innovative treatment strategies. Notably, existing mouse models have limited utility due to heterogenous and untypical phenotypes of AVM lesions. Here we developed a novel mouse model of sporadic BAVM that is consistent with clinical manifestations in humans. Mice with <i>Braf</i>^V600E mutations in brain ECs developed BAVM closely resembled that of human lesions. This strategy successfully induced BAVMs in mice across different age groups and within various brain regions. Pathological features of BAVM were primarily dilated blood vessels with reduced vascular wall stability, accompanied by spontaneous hemorrhage and neuroinflammation. Single-cell sequencing revealed differentially expressed genes that were related to the cytoskeleton, cell motility, and intercellular junctions. Early administration of Dabrafenib was found to be effective in slowing the progression of BAVMs; however, its efficacy in treating established BAVM lesions remained uncertain. Taken together, our proposed approach successfully induced BAVM that closely resembled human BAVM lesions in mice, rendering the model suitable for investigating the pathogenesis of BAVM and assessing potential therapeutic strategies.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 3","pages":"441 - 460"},"PeriodicalIF":9.2,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140849011","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: 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/s10456-024-09919-7","DOIUrl":"10.1007/s10456-024-09919-7","url":null,"abstract":"","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 3","pages":"375 - 377"},"PeriodicalIF":9.2,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854145","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":"Systemic glucocorticoids use in post-COVID-syndrome patients does not affect retinal microcirculation","authors":"T. Kuchler,&nbsp;C. Schmaderer","doi":"10.1007/s10456-024-09926-8","DOIUrl":"10.1007/s10456-024-09926-8","url":null,"abstract":"","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 3","pages":"287 - 291"},"PeriodicalIF":9.2,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854146","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":"Systemic glucocorticoids link to long-term microvascular injury in COVID-19","authors":"Qian Yang,&nbsp;Cai Yun Xia,&nbsp;Ying Cai,&nbsp;Yan Fang Zhang,&nbsp;Dao Ting Li,&nbsp;Shu Qi Wu,&nbsp;Peng Hu","doi":"10.1007/s10456-024-09923-x","DOIUrl":"10.1007/s10456-024-09923-x","url":null,"abstract":"","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 3","pages":"285 - 286"},"PeriodicalIF":9.2,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140661705","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":"Interleukin-6 drives endothelial glycocalyx damage in COVID-19 and bacterial sepsis","authors":"Carolin Christina Drost,&nbsp;Alexandros Rovas,&nbsp;Irina Osiaevi,&nbsp;Klaus Schughart,&nbsp;Alexander Lukasz,&nbsp;Wolfgang A. Linke,&nbsp;Hermann Pavenstädt,&nbsp;Philipp Kümpers","doi":"10.1007/s10456-024-09916-w","DOIUrl":"10.1007/s10456-024-09916-w","url":null,"abstract":"<div><p>Damage of the endothelial glycocalyx (eGC) plays a central role in the development of vascular hyperpermeability and organ damage during systemic inflammation. However, the specific signalling pathways for eGC damage remain poorly defined. Aim of this study was to combine sublingual video-microscopy, plasma proteomics and live cell imaging to uncover further pathways of eGC damage in patients with coronavirus disease 2019 (COVID-19) or bacterial sepsis. This secondary analysis of the prospective multicenter MICROCODE study included 22 patients with COVID-19 and 43 patients with bacterial sepsis admitted to intermediate or intensive care units and 10 healthy controls. Interleukin-6 (IL-6) was strongly associated with damaged eGC and correlated both with eGC dimensions (r_s=0.36, <i>p</i> = 0.0015) and circulating eGC biomarkers. In vitro, IL-6 reduced eGC height and coverage, which was inhibited by blocking IL-6 signalling with the anti-IL-6 receptor antibody tocilizumab or the Janus kinase inhibitor tofacitinib. Exposure of endothelial cells to 5% serum from COVID-19 or sepsis patients resulted in a significant decrease in eGC height, which was attenuated by co-incubation with tocilizumab. In an external COVID-19 cohort of 219 patients from Massachusetts General Hospital, a previously identified proteomic eGC signature correlated with IL-6 (r_s=-0.58, <i>p</i> &lt; 0.0001) and predicted the combined endpoint of 28-day mortality and/or intubation (ROC-AUC: 0.86 [95% CI: 0.81–0.91], <i>p</i> &lt; 0.001). The data suggest that IL-6 may significantly drive eGC damage in COVID-19 and bacterial sepsis. Our findings provide valuable insights into pathomechanisms of vascular dysfunction during systemic inflammation and highlight the need for further in vivo studies.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 3","pages":"411 - 422"},"PeriodicalIF":9.2,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-024-09916-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140580247","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":"Navigating tumor angiogenesis: therapeutic perspectives and myeloid cell regulation mechanism","authors":"Fan Yang,&nbsp;Gloria Lee,&nbsp;Yi Fan","doi":"10.1007/s10456-024-09913-z","DOIUrl":"10.1007/s10456-024-09913-z","url":null,"abstract":"<div><p>Sustained angiogenesis stands as a hallmark of cancer. The intricate vascular tumor microenvironment fuels cancer progression and metastasis, fosters therapy resistance, and facilitates immune evasion. Therapeutic strategies targeting tumor vasculature have emerged as transformative for cancer treatment, encompassing anti-angiogenesis, vessel normalization, and endothelial reprogramming. Growing evidence suggests the dynamic regulation of tumor angiogenesis by infiltrating myeloid cells, such as macrophages, myeloid-derived suppressor cells (MDSCs), and neutrophils. Understanding these regulatory mechanisms is pivotal in paving the way for successful vasculature-targeted cancer treatments. Therapeutic interventions aimed to disrupt myeloid cell-mediated tumor angiogenesis may reshape tumor microenvironment and overcome tumor resistance to radio/chemotherapy and immunotherapy.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 3","pages":"333 - 349"},"PeriodicalIF":9.2,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-024-09913-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579858","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}