Angiogenesis最新文献

{"title":"2022 14th HHT International Scientific Conference Abstracts","authors":"","doi":"10.1007/s10456-023-09887-4","DOIUrl":"10.1007/s10456-023-09887-4","url":null,"abstract":"","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"26 1","pages":"1 - 25"},"PeriodicalIF":9.8,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-023-09887-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10183063","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":"Reply to “Embracing imatinib: a novel approach to safeguarding the endothelial barrier in patients with COVID-19”","authors":"Xiaoming Wu, Jialan Shi","doi":"10.1007/s10456-023-09894-5","DOIUrl":"10.1007/s10456-023-09894-5","url":null,"abstract":"","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"26 4","pages":"485 - 486"},"PeriodicalIF":9.8,"publicationDate":"2023-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-023-09894-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41188891","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":"The modes of angiogenesis: an updated perspective","authors":"Andrew C. Dudley,&nbsp;Arjan W. Griffioen","doi":"10.1007/s10456-023-09895-4","DOIUrl":"10.1007/s10456-023-09895-4","url":null,"abstract":"<div><p>Following the process of vasculogenesis during development, angiogenesis generates new vascular structures through a variety of different mechanisms or modes. These different modes of angiogenesis involve, for example, increasing microvasculature density by sprouting of endothelial cells, splitting of vessels to increase vascular surface area by intussusceptive angiogenesis, fusion of capillaries to increase blood flow by coalescent angiogenesis, and the recruitment of non-endothelial cells by vasculogenic mimicry. The recent reporting on coalescent angiogenesis as a new mode of vessel formation warrants a brief overview of angiogenesis mechanisms to provide a more complete picture. The journal <i>Angiogenesis</i> is devoted to the delineation of the different modes and mechanisms that collectively dictate blood vessel formation, inhibition, and function in health and disease.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"26 4","pages":"477 - 480"},"PeriodicalIF":9.8,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41188893","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: Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation","authors":"Timon Kuchler,&nbsp;Roman Günthner,&nbsp;Andrea Ribeiro,&nbsp;Renate Hausinger,&nbsp;Lukas Streese,&nbsp;Anna Wöhnl,&nbsp;Veronika Kesseler,&nbsp;Johanna Negele,&nbsp;Tarek Assali,&nbsp;Javier Carbajo-Lozoya,&nbsp;Maciej Lech,&nbsp;Heike Schneider,&nbsp;Kristina Adorjan,&nbsp;Hans Christian Stubbe,&nbsp;Henner Hanssen,&nbsp;Konstantin Kotilar,&nbsp;Bernhard Haller,&nbsp;Uwe Heemann,&nbsp;Christoph Schmaderer","doi":"10.1007/s10456-023-09892-7","DOIUrl":"10.1007/s10456-023-09892-7","url":null,"abstract":"","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"26 4","pages":"565 - 565"},"PeriodicalIF":9.8,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-023-09892-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10062002","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":"Aging impairs the ability of vascular endothelial stem cells to generate endothelial cells in mice","authors":"Shota Shimizu,&nbsp;Tomohiro Iba,&nbsp;Hisamichi Naito,&nbsp;Fitriana Nur Rahmawati,&nbsp;Hirotaka Konishi,&nbsp;Weizhen Jia,&nbsp;Fumitaka Muramatsu,&nbsp;Nobuyuki Takakura","doi":"10.1007/s10456-023-09891-8","DOIUrl":"10.1007/s10456-023-09891-8","url":null,"abstract":"<div><p>Tissue-resident vascular endothelial stem cells (VESCs), marked by expression of CD157, possess long-term repopulating potential and contribute to vascular regeneration and homeostasis in mice. Stem cell exhaustion is regarded as one of the hallmarks of aging and is being extensively studied in several types of tissue-resident stem cells; however, how aging affects VESCs has not been clarified yet. In the present study, we isolated VESCs from young and aged mice to compare their potential to differentiate into endothelial cells in vitro and in vivo. Here, we report that the number of liver endothelial cells (ECs) including VESCs was lower in aged (27–28 month-old) than young (2–3 month-old) mice. In vitro culture of primary VESCs revealed that the potential to generate ECs is impaired in aged VESCs isolated from liver and lung relative to young VESCs. Orthotopic transplantation of VESCs showed that aged VESCs and their progeny expand less efficiently than their young counterparts when transplanted into aged mice, but they are equally functional in young recipients. Gene expression analysis indicated that inflammatory signaling was more activated in aged ECs including VESCs. Using single-cell RNA sequencing data from the Tabula Muris Consortium, we show that T cells and monocyte/macrophage lineage cells including Kupffer cells are enriched in the aged liver. These immune cells produce IL-1β and several chemokines, suggesting the possible involvement of age-associated inflammation in the functional decline of VESCs with age.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"26 4","pages":"567 - 580"},"PeriodicalIF":9.8,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-023-09891-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41188886","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":"Embracing Imatinib: a novel approach to safeguarding the endothelial barrier in patients with COVID-19","authors":"Chia Siang Kow,&nbsp;Dinesh Sangarran Ramachandram,&nbsp;Syed Shahzad Hasan","doi":"10.1007/s10456-023-09889-2","DOIUrl":"10.1007/s10456-023-09889-2","url":null,"abstract":"<div><p>Imatinib, an ABL tyrosine-kinase inhibitor, shows promise in restoring endothelial barrier function in patients with COVID-19, thus, preventing cytokine leakage from the alveolar compartment to the systemic compartment. COVID-19 is characterized by an alveolar cytokine storm, and imatinib has been shown to strengthen the endothelial barrier and mitigate alveolar inflammatory responses by modulating NF-κB signaling. Incorporating imatinib into COVID-19 treatment strategies offers a novel approach to safeguard the endothelial barrier and address the complex pathophysiology of the disease, including its potential implications in long COVID. Given that endothelial dysfunction plays a central role in COVID-19 progression and long COVID development, protecting the endothelial barrier during acute infection is crucial in preventing the persistent endothelial dysfunction associated with long COVID.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"26 4","pages":"481 - 483"},"PeriodicalIF":9.8,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41188888","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":"VEGF-A plasma levels are associated with impaired DLCO and radiological sequelae in long COVID patients","authors":"Aurélien Philippe,&nbsp;Sven Günther,&nbsp;Jeanne Rancic,&nbsp;Pauline Cavagna,&nbsp;Bertrand Renaud,&nbsp;Nicolas Gendron,&nbsp;Elie Mousseaux,&nbsp;Thông Hua-Huy,&nbsp;Guillaume Reverdito,&nbsp;Benjamin Planquette,&nbsp;Olivier Sanchez,&nbsp;Pascale Gaussem,&nbsp;Dominique Salmon,&nbsp;Jean-Luc Diehl,&nbsp;David M. Smadja","doi":"10.1007/s10456-023-09890-9","DOIUrl":"10.1007/s10456-023-09890-9","url":null,"abstract":"<div><h3>Background</h3><p>Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is characterized by persistent clinical symptoms following COVID-19.</p><h3>Objective</h3><p>To correlate biomarkers of endothelial dysfunction with persistent clinical symptoms and pulmonary function defects at distance from COVID-19.</p><h3>Methods</h3><p>Consecutive patients with long COVID-19 suspicion were enrolled. A panel of endothelial biomarkers was measured in each patient during clinical evaluation and pulmonary function test (PFT).</p><h3>Results</h3><p>The study included 137 PASC patients, mostly male (68%), with a median age of 55 years. A total of 194 PFTs were performed between months 3 and 24 after an episode of SARS-CoV-2 infection. We compared biomarkers evaluated in PASC patients with 20 healthy volunteers (HVs) and acute hospitalized COVID-19 patients (<i>n</i> = 88). The study found that angiogenesis-related biomarkers and von Willebrand factor (VWF) levels were increased in PASC patients compared to HVs without increased inflammatory or platelet activation markers. Moreover, VEGF-A and VWF were associated with persistent lung CT scan lesions and impaired diffusing capacity of the lungs for carbon monoxide (DLCO) measurement. By employing a Cox proportional hazards model adjusted for age, sex, and body mass index, we further confirmed the accuracy of VEGF-A and VWF. Following adjustment, VEGF-A emerged as the most significant predictive factor associated with persistent lung CT scan lesions and impaired DLCO measurement.</p><h3>Conclusion</h3><p>VEGF-A is a relevant predictive factor for DLCO impairment and radiological sequelae in PASC. Beyond being a biomarker, we hypothesize that the persistence of angiogenic disorders may contribute to long COVID symptoms.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 1","pages":"51 - 66"},"PeriodicalIF":9.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9912113","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":"Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation","authors":"Timon Kuchler,&nbsp;Roman Günthner,&nbsp;Andrea Ribeiro,&nbsp;Renate Hausinger,&nbsp;Lukas Streese,&nbsp;Anna Wöhnl,&nbsp;Veronika Kesseler,&nbsp;Johanna Negele,&nbsp;Tarek Assali,&nbsp;Javier Carbajo-Lozoya,&nbsp;Maciej Lech,&nbsp;Heike Schneider,&nbsp;Kristina Adorjan,&nbsp;Hans Christian Stubbe,&nbsp;Henner Hanssen,&nbsp;Konstantin Kotilar,&nbsp;Bernhard Haller,&nbsp;Uwe Heemann,&nbsp;Christoph Schmaderer","doi":"10.1007/s10456-023-09885-6","DOIUrl":"10.1007/s10456-023-09885-6","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still poses a diagnostic and treatment challenge for physicians.&lt;/p&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;In this prospective observational cohort study, we analyzed the retinal microcirculation using Retinal Vessel Analysis (RVA) in a cohort of patients with PCS and compared it to an age- and gender-matched healthy cohort (&lt;i&gt;n&lt;/i&gt; = 41, matched out of &lt;i&gt;n&lt;/i&gt; = 204).&lt;/p&gt;&lt;h3&gt;Measurements and main results&lt;/h3&gt;&lt;p&gt;PCS patients exhibit persistent endothelial dysfunction (ED), as indicated by significantly lower venular flicker-induced dilation (vFID; 3.42% ± 1.77% vs. 4.64% ± 2.59%; &lt;i&gt;p&lt;/i&gt; = 0.02), narrower central retinal artery equivalent (CRAE; 178.1 [167.5–190.2] vs. 189.1 [179.4–197.2], &lt;i&gt;p&lt;/i&gt; = 0.01) and lower arteriolar-venular ratio (AVR; (0.84 [0.8–0.9] vs. 0.88 [0.8–0.9], &lt;i&gt;p&lt;/i&gt; = 0.007). When combining AVR and vFID, predicted scores reached good ability to discriminate groups (area under the curve: 0.75). Higher PCS severity scores correlated with lower AVR (&lt;i&gt;R&lt;/i&gt; = − 0.37 &lt;i&gt;p&lt;/i&gt; = 0.017). The association of microvascular changes with PCS severity were amplified in PCS patients exhibiting higher levels of inflammatory parameters.&lt;/p&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;Our results demonstrate that prolonged endothelial dysfunction is a hallmark of PCS, and impairments of the microcirculation seem to explain ongoing symptoms in patients. As potential therapies for PCS emerge, RVA parameters may become relevant as clinical biomarkers for diagnosis and therapy management.&lt;/p&gt;&lt;h3&gt;Trial registration&lt;/h3&gt;&lt;p&gt;This study was previously registered at ClinicalTrials (“All Eyes on PCS—Analysis of the Retinal Microvasculature in Patients with Post-COVID-19 Syndrome”. NCT05635552. https://clinicaltrials.gov/ct2/show/NCT05635552).&lt;/p&gt;&lt;h3&gt;Graphical abstract&lt;/h3&gt;&lt;p&gt;Persistent endothelial dysfunction in post-COVID-19 syndrome. Acute SARS-CoV-2 infection indirectly or directly causes endotheliitis in patients. &lt;i&gt;N&lt;/i&gt; = 41 PCS patients were recruited and retinal vessel analysis was performed to assess microvascular endothelial function. Images of SVA and DVA are illustrative for RVA data analysis. For each PCS patient and healthy cohort, venular vessel diameter of the three measurement cycles was calculated and plotted on a diameter-time curve. Patients exhibited reduced flicker-induced dilation in veins (vFID) measured by dynamic vessel analysis (DVA) and lower central retinal arteriolar equivalent (CRAE) and arteriolar-venular ratio (AVR) and a tendency towards higher central retinal venular equivalent (CRVE) when compared to SARS-CoV-2 infection naïve participants. Created with BioRender.com&lt;/p&gt;\u0000 &lt;div&gt;&lt;figure&gt;&lt;div&gt;&lt;div&gt;&lt;picture&gt;&lt;source&gt;&lt;img&gt;&lt;/source&gt;&lt;/picture&gt;&lt;/div&gt;&lt;/div&gt;&lt;/figure&gt;&lt;/div&gt;\u0000","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"26 4","pages":"547 - 563"},"PeriodicalIF":9.8,"publicationDate":"2023-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-023-09885-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41188890","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":"Phenotypic screening in Organ-on-a-Chip systems: a 1537 kinase inhibitor library screen on a 3D angiogenesis assay","authors":"Camilla Soragni,&nbsp;Karla Queiroz,&nbsp;Chee Ping Ng,&nbsp;Arthur Stok,&nbsp;Thomas Olivier,&nbsp;Dora Tzagkaraki,&nbsp;Jeroen Heijmans,&nbsp;Johnny Suijker,&nbsp;Sander P. M. de Ruiter,&nbsp;Aleksandra Olczyk,&nbsp;Marleen Bokkers,&nbsp;Frederik Schavemaker,&nbsp;Sebastian J. Trietsch,&nbsp;Henriëtte L. Lanz,&nbsp;Paul Vulto,&nbsp;Jos Joore","doi":"10.1007/s10456-023-09888-3","DOIUrl":"10.1007/s10456-023-09888-3","url":null,"abstract":"<div><p>Modern drug development increasingly requires comprehensive models that can be utilized in the earliest stages of compound and target discovery. Here we report a phenotypic screening exercise in a high-throughput Organ-on-a-Chip setup. We assessed the inhibitory effect of 1537 protein kinase inhibitors in an angiogenesis assay. Over 4000 micro-vessels were grown under perfusion flow in microfluidic chips, exposed to a cocktail of pro-angiogenic factors and subsequently exposed to the respective kinase inhibitors. Efficacy of compounds was evaluated by reduced angiogenic sprouting, whereas reduced integrity of the main micro-vessel was taken as a measure for toxicity. The screen yielded 53 hits with high anti-angiogenicity and low toxicity, of which 44 were previously unassociated with angiogenic pathways. This study demonstrates that Organ-on-a-Chip models can be screened in high numbers to identify novel compounds and targets. This will ultimately reduce bias in early-stage drug development and increases probability to identify first in class compounds and targets for today’s intractable diseases.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 1","pages":"37 - 49"},"PeriodicalIF":9.2,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10881651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10229199","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":"FOXO1 promotes endothelial cell elongation and angiogenesis by up-regulating the phosphorylation of myosin light chain 2","authors":"Kiyomi Tsuji-Tamura,&nbsp;Minetaro Ogawa","doi":"10.1007/s10456-023-09884-7","DOIUrl":"10.1007/s10456-023-09884-7","url":null,"abstract":"<div><p>The forkhead box O1 (FOXO1) is an important transcription factor related to proliferation, metabolism, and homeostasis, while the major phenotype of FOXO1-null mice is abnormal vascular morphology, such as vessel enlargement and dilation. In in vitro mouse embryonic stem cell (ESC)-differentiation system, <i>Foxo1</i>^−/− vascular endothelial cells (ECs) fail to elongate, and mimic the abnormalities of FOXO1-deficiency in vivo. Here, we identified the <i>PPP1R14C</i> gene as the FOXO1 target genes responsible for elongating using transcriptome analyses in ESC-derived ECs (ESC-ECs), and found that the FOXO1-PPP1R14C-myosin light chain 2 (MLC2) axis is required for EC elongation during angiogenesis. MLC2 is phosphorylated by MLC kinase (MLCK) and dephosphorylated by MLC phosphatase (MLCP). PPP1R14C is an inhibitor of PP1, the catalytic subunit of MLCP. The abnormal morphology of <i>Foxo1</i>^−/− ESC-ECs was associated with low level of PPP1R14C and loss of MLC2 phosphorylation, which were reversed by PPP1R14C-introduction. Knockdown of either FOXO1 or PPP1R14C suppressed vascular cord formation and reduced MLC2 phosphorylation in human ECs (HUVECs). The mouse and human PPP1R14C locus possesses an enhancer element containing conserved FOXO1-binding motifs. In vivo chemical inhibition of MLC2 phosphorylation caused dilated vascular structures in mouse embryos. Furthermore, <i>foxo1</i> or <i>ppp1r14c</i>-knockdown zebrafish exhibited vascular malformations, which were also restored by PPP1R14C-introduction. Mechanistically, FOXO1 suppressed MLCP activity by up-regulating <i>PPP1R14C</i> expression, thereby promoting MLC2 phosphorylation and EC elongation, which are necessary for vascular development. Given the importance of MLC2 phosphorylation in cell morphogenesis, this study may provide novel insights into the role of FOXO1 in control of angiogenesis.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"26 4","pages":"523 - 545"},"PeriodicalIF":9.8,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10223671","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}