AngiogenesisPub Date : 2023-08-02DOI: 10.1007/s10456-023-09889-2
Chia Siang Kow, Dinesh Sangarran Ramachandram, Syed Shahzad Hasan
{"title":"Embracing Imatinib: a novel approach to safeguarding the endothelial barrier in patients with COVID-19","authors":"Chia Siang Kow, Dinesh Sangarran Ramachandram, 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}
AngiogenesisPub Date : 2023-07-28DOI: 10.1007/s10456-023-09885-6
Timon Kuchler, Roman Günthner, Andrea Ribeiro, Renate Hausinger, Lukas Streese, Anna Wöhnl, Veronika Kesseler, Johanna Negele, Tarek Assali, Javier Carbajo-Lozoya, Maciej Lech, Heike Schneider, Kristina Adorjan, Hans Christian Stubbe, Henner Hanssen, Konstantin Kotilar, Bernhard Haller, Uwe Heemann, Christoph Schmaderer
{"title":"Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation","authors":"Timon Kuchler, Roman Günthner, Andrea Ribeiro, Renate Hausinger, Lukas Streese, Anna Wöhnl, Veronika Kesseler, Johanna Negele, Tarek Assali, Javier Carbajo-Lozoya, Maciej Lech, Heike Schneider, Kristina Adorjan, Hans Christian Stubbe, Henner Hanssen, Konstantin Kotilar, Bernhard Haller, Uwe Heemann, Christoph Schmaderer","doi":"10.1007/s10456-023-09885-6","DOIUrl":"10.1007/s10456-023-09885-6","url":null,"abstract":"<div><h3>Background</h3><p>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.</p><h3>Methods</h3><p>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 (<i>n</i> = 41, matched out of <i>n</i> = 204).</p><h3>Measurements and main results</h3><p>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%; <i>p</i> = 0.02), narrower central retinal artery equivalent (CRAE; 178.1 [167.5–190.2] vs. 189.1 [179.4–197.2], <i>p</i> = 0.01) and lower arteriolar-venular ratio (AVR; (0.84 [0.8–0.9] vs. 0.88 [0.8–0.9], <i>p</i> = 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 (<i>R</i> = − 0.37 <i>p</i> = 0.017). The association of microvascular changes with PCS severity were amplified in PCS patients exhibiting higher levels of inflammatory parameters.</p><h3>Conclusion</h3><p>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.</p><h3>Trial registration</h3><p>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).</p><h3>Graphical abstract</h3><p>Persistent endothelial dysfunction in post-COVID-19 syndrome. Acute SARS-CoV-2 infection indirectly or directly causes endotheliitis in patients. <i>N</i> = 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</p>\u0000 <div><figure><div><div><picture><source><img></source></picture></div></div></figure></div>\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}
AngiogenesisPub Date : 2023-07-26DOI: 10.1007/s10456-023-09888-3
Camilla Soragni, Karla Queiroz, Chee Ping Ng, Arthur Stok, Thomas Olivier, Dora Tzagkaraki, Jeroen Heijmans, Johnny Suijker, Sander P. M. de Ruiter, Aleksandra Olczyk, Marleen Bokkers, Frederik Schavemaker, Sebastian J. Trietsch, Henriëtte L. Lanz, Paul Vulto, Jos Joore
{"title":"Phenotypic screening in Organ-on-a-Chip systems: a 1537 kinase inhibitor library screen on a 3D angiogenesis assay","authors":"Camilla Soragni, Karla Queiroz, Chee Ping Ng, Arthur Stok, Thomas Olivier, Dora Tzagkaraki, Jeroen Heijmans, Johnny Suijker, Sander P. M. de Ruiter, Aleksandra Olczyk, Marleen Bokkers, Frederik Schavemaker, Sebastian J. Trietsch, Henriëtte L. Lanz, Paul Vulto, 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}
AngiogenesisPub Date : 2023-06-16DOI: 10.1007/s10456-023-09883-8
Floor M. E. G. Steegh, Anke A. Keijbeck, Patrick A. de Hoogt, Timo Rademakers, Alfons J. H. M. Houben, Koen D. Reesink, Coen D. A. Stehouwer, Mat J. A. P. Daemen, Carine J. Peutz-Kootstra
{"title":"Capillary rarefaction: a missing link in renal and cardiovascular disease?","authors":"Floor M. E. G. Steegh, Anke A. Keijbeck, Patrick A. de Hoogt, Timo Rademakers, Alfons J. H. M. Houben, Koen D. Reesink, Coen D. A. Stehouwer, Mat J. A. P. Daemen, Carine J. Peutz-Kootstra","doi":"10.1007/s10456-023-09883-8","DOIUrl":"10.1007/s10456-023-09883-8","url":null,"abstract":"<div><p>Patients with chronic kidney disease (CKD) have an increased risk for cardiovascular morbidity and mortality. Capillary rarefaction may be both one of the causes as well as a consequence of CKD and cardiovascular disease. We reviewed the published literature on human biopsy studies and conclude that renal capillary rarefaction occurs independently of the cause of renal function decline. Moreover, glomerular hypertrophy may be an early sign of generalized endothelial dysfunction, while peritubular capillary loss occurs in advanced renal disease. Recent studies with non-invasive measurements show that capillary rarefaction is detected systemically (e.g., in the skin) in individuals with albuminuria, as sign of early CKD and/or generalized endothelial dysfunction. Decreased capillary density is found in omental fat, muscle and heart biopsies of patients with advanced CKD as well as in skin, fat, muscle, brain and heart biopsies of individuals with cardiovascular risk factors. No biopsy studies have yet been performed on capillary rarefaction in individuals with early CKD. At present it is unknown whether individuals with CKD and cardiovascular disease merely share the same risk factors for capillary rarefaction, or whether there is a causal relationship between rarefaction in renal and systemic capillaries. Further studies on renal and systemic capillary rarefaction, including their temporal relationship and underlying mechanisms are needed. This review stresses the importance of preserving and maintaining capillary integrity and homeostasis in the prevention and management of renal and cardiovascular disease.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"27 1","pages":"23 - 35"},"PeriodicalIF":9.2,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9640407","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}
AngiogenesisPub Date : 2023-05-15DOI: 10.1007/s10456-023-09880-x
Carolin C. Drost, Andreas Unger, Wolfgang A. Linke, Hans Vink, Philipp Kümpers
{"title":"The dynamics of the endothelial glycocalyx: a rare snapshot by electron microscopy","authors":"Carolin C. Drost, Andreas Unger, Wolfgang A. Linke, Hans Vink, Philipp Kümpers","doi":"10.1007/s10456-023-09880-x","DOIUrl":"10.1007/s10456-023-09880-x","url":null,"abstract":"","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"26 4","pages":"487 - 491"},"PeriodicalIF":9.8,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-023-09880-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41188892","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}
AngiogenesisPub Date : 2023-04-29DOI: 10.1007/s10456-023-09877-6
Pauline Puylaert, Lynn Roth, Melissa Van Praet, Isabel Pintelon, Catalina Dumitrascu, Alexander van Nuijs, Greta Klejborowska, Pieter-Jan Guns, Tom Vanden Berghe, Koen Augustyns, Guido R. Y. De Meyer, Wim Martinet
{"title":"Effect of erythrophagocytosis-induced ferroptosis during angiogenesis in atherosclerotic plaques","authors":"Pauline Puylaert, Lynn Roth, Melissa Van Praet, Isabel Pintelon, Catalina Dumitrascu, Alexander van Nuijs, Greta Klejborowska, Pieter-Jan Guns, Tom Vanden Berghe, Koen Augustyns, Guido R. Y. De Meyer, Wim Martinet","doi":"10.1007/s10456-023-09877-6","DOIUrl":"10.1007/s10456-023-09877-6","url":null,"abstract":"<div><p>Intraplaque (IP) angiogenesis is a key feature of advanced atherosclerotic plaques. Because IP vessels are fragile and leaky, erythrocytes are released and phagocytosed by macrophages (erythrophagocytosis), which leads to high intracellular iron content, lipid peroxidation and cell death. In vitro experiments showed that erythrophagocytosis by macrophages induced non-canonical ferroptosis, an emerging type of regulated necrosis that may contribute to plaque destabilization. Erythrophagocytosis-induced ferroptosis was accompanied by increased expression of heme-oxygenase 1 and ferritin, and could be blocked by co-treatment with third generation ferroptosis inhibitor UAMC-3203. Both heme-oxygenase 1 and ferritin were also expressed in erythrocyte-rich regions of carotid plaques from <i>ApoE</i><sup><i>−/−</i></sup> <i>Fbn1</i><sup><i>C1039G+/−</i></sup> mice, a model of advanced atherosclerosis with IP angiogenesis. The effect of UAMC-3203 (12.35 mg/kg/day) on atherosclerosis was evaluated in <i>ApoE</i><sup><i>−/−</i></sup> <i>Fbn1</i><sup><i>C1039G+/−</i></sup> mice fed a western-type diet (WD) for 12 weeks (n = 13 mice/group) or 20 weeks (n = 16–21 mice/group) to distinguish between plaques without and with established IP angiogenesis, respectively. A significant decrease in carotid plaque thickness was observed after 20 weeks WD (87 ± 19 μm vs. 166 ± 20 μm, <i>p</i> = 0.006), particularly in plaques with confirmed IP angiogenesis or hemorrhage (108 ± 35 μm vs. 322 ± 40 μm, <i>p</i> = 0.004). This effect was accompanied by decreased IP heme-oxygenase 1 and ferritin expression. UAMC-3203 did not affect carotid plaques after 12 weeks WD or plaques in the aorta, which typically do not develop IP angiogenesis. Altogether, erythrophagocytosis-induced ferroptosis during IP angiogenesis leads to larger atherosclerotic plaques, an effect that can be prevented by ferroptosis inhibitor UAMC-3203.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"26 4","pages":"505 - 522"},"PeriodicalIF":9.8,"publicationDate":"2023-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-023-09877-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41188887","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}
AngiogenesisPub Date : 2023-04-29DOI: 10.1007/s10456-023-09879-4
Doryssa Hermans, Carla Rodriguez-Mogeda, Hannelore Kemps, Annelies Bronckaers, Helga E. de Vries, Bieke Broux
{"title":"Correction: Nectins and Nectin-like molecules drive vascular development and barrier function","authors":"Doryssa Hermans, Carla Rodriguez-Mogeda, Hannelore Kemps, Annelies Bronckaers, Helga E. de Vries, Bieke Broux","doi":"10.1007/s10456-023-09879-4","DOIUrl":"10.1007/s10456-023-09879-4","url":null,"abstract":"","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"26 3","pages":"363 - 363"},"PeriodicalIF":9.8,"publicationDate":"2023-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9792381","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}
AngiogenesisPub Date : 2023-04-15DOI: 10.1007/s10456-023-09876-7
Andrew C. Dudley, Arjan W. Griffioen
{"title":"Pathological angiogenesis: mechanisms and therapeutic strategies","authors":"Andrew C. Dudley, Arjan W. Griffioen","doi":"10.1007/s10456-023-09876-7","DOIUrl":"10.1007/s10456-023-09876-7","url":null,"abstract":"<div><p>In multicellular organisms, angiogenesis, the formation of new blood vessels from pre-existing ones, is an essential process for growth and development. Different mechanisms such as vasculogenesis, sprouting, intussusceptive, and coalescent angiogenesis, as well as vessel co-option, vasculogenic mimicry and lymphangiogenesis, underlie the formation of new vasculature. In many pathological conditions, such as cancer, atherosclerosis, arthritis, psoriasis, endometriosis, obesity and SARS-CoV-2(COVID-19), developmental angiogenic processes are recapitulated, but are often done so without the normal feedback mechanisms that regulate the ordinary spatial and temporal patterns of blood vessel formation. Thus, pathological angiogenesis presents new challenges yet new opportunities for the design of vascular-directed therapies. Here, we provide an overview of recent insights into blood vessel development and highlight novel therapeutic strategies that promote or inhibit the process of angiogenesis to stabilize, reverse, or even halt disease progression. In our review, we will also explore several additional aspects (the angiogenic switch, hypoxia, angiocrine signals, endothelial plasticity, vessel normalization, and endothelial cell anergy) that operate in parallel to canonical angiogenesis mechanisms and speculate how these processes may also be targeted with anti-angiogenic or vascular-directed therapies.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"26 3","pages":"313 - 347"},"PeriodicalIF":9.8,"publicationDate":"2023-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-023-09876-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9791304","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}
AngiogenesisPub Date : 2023-04-05DOI: 10.1007/s10456-023-09874-9
Khushbu Rauniyar, Honey Bokharaie, Michael Jeltsch
{"title":"Expansion and collapse of VEGF diversity in major clades of the animal kingdom","authors":"Khushbu Rauniyar, Honey Bokharaie, Michael Jeltsch","doi":"10.1007/s10456-023-09874-9","DOIUrl":"10.1007/s10456-023-09874-9","url":null,"abstract":"<div><p>Together with the platelet-derived growth factors (PDGFs), the vascular endothelial growth factors (VEGFs) form the PDGF/VEGF subgroup among cystine knot growth factors. The evolutionary relationships within this subgroup have not been examined thoroughly to date. Here, we comprehensively analyze the PDGF/VEGF growth factors throughout all animal phyla and propose a phylogenetic tree. Vertebrate whole-genome duplications play a role in expanding PDGF/VEGF diversity, but several limited duplications are necessary to account for the temporal pattern of emergence. The phylogenetically oldest PDGF/VEGF-like growth factor likely featured a C-terminus with a BR3P signature, a hallmark of the modern-day lymphangiogenic growth factors VEGF-C and VEGF-D. Some younger VEGF genes, such as <i>VEGFB</i> and <i>PGF</i>, appeared completely absent in important vertebrate clades such as birds and amphibia, respectively. In contrast, individual PDGF/VEGF gene duplications frequently occurred in fish on top of the known fish-specific whole-genome duplications. The lack of precise counterparts for human genes poses limitations but also offers opportunities for research using organisms that diverge considerably from humans.</p><h3>Graphical abstract</h3><p>Sources for the graphical abstract: 326 MYA and older [1]; 72–240 MYA [2]; 235–65 MYA [3]</p>\u0000 <div><figure><div><div><picture><source><img></source></picture></div></div></figure></div>\u0000 </div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"26 3","pages":"437 - 461"},"PeriodicalIF":9.8,"publicationDate":"2023-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-023-09874-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9787111","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}