{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T01:28:14Z","timestamp":1786498094403,"version":"build-2736575974"},"reference-count":141,"publisher":"Georg Thieme Verlag KG","issue":"CP","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TH Open"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chimeric antigen receptor (CAR) T cell therapy has transformed the management of hematologic malignancies, yet its clinical success is tempered by severe immune-mediated toxicities, including cytokine-release syndrome (CRS) and immune effector cell\u2013associated neurotoxicity syndrome (ICANS), often accompanied by CAR T cell therapy-related coagulopathy (CARAC). Converging evidence identifies therapy-related endotheliopathy as a central pathophysiological link between cytokine excess, hemostatic dysregulation, capillary leak, and organ injury. Parallel efforts aim to identify circulating biomarkers that can signal emerging toxicity before clinical deterioration. This review summarizes the biological basis of endotheliopathy during CAR T cell therapy, with particular emphasis on two interconnected regulatory systems: the von Willebrand factor (VWF)\/ADAMTS13 axis, which governs platelet adhesion and microvascular thrombosis, and the angiopoietin (Ang)\u2013tyrosine kinase receptor Tie2 signaling pathway, which regulates endothelial stability and vascular permeability. Dysregulation of these pathways drives the shift from adaptive immunothrombosis to pathological endothelial injury, characterized by loss of anticoagulant control, barrier disruption, and microvascular instability. Clinical studies show that alterations in the VWF\/ADAMTS13 balance and increases in the Ang-2\/Ang-1 ratio correlate with CRS and ICANS severity and may precede overt toxicity, highlighting their potential as markers of endothelial vulnerability. Defining actionable biomarker thresholds and evaluating endothelial-targeted interventions are key priorities for improving the safety and precision of CAR T cell therapy.<\/jats:p>","DOI":"10.1055\/a-2923-1208","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:43:06Z","timestamp":1784940186000},"source":"Crossref","is-referenced-by-count":0,"special_numbering":"S","title":["Endotheliopathy in CAR T-Cell Therapy: Mechanistic Insights into the VWF\/ADAMTS13 Axis and the Angiopoietin\u2013Tie2 Pathway"],"prefix":"10.1055","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6905-650X","authenticated-orcid":false,"given":"S\u00e9v\u00e9rine","family":"de Bruijn","sequence":"additional","affiliation":[{"name":"Antwerp University Hospital, Antwerp, Belgium","place":["Edegem"],"department":["Department of Haematology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Vangenechten","sequence":"additional","affiliation":[{"name":"Antwerp University Hospital, Antwerp, Belgium","place":["Edegem"],"department":["Department of Haematology"]},{"name":"Antwerp University Hospital, Antwerpen, Belgium","place":["Edegem"],"department":["Haemostasis and Thrombosis Research Center"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Anguille","sequence":"additional","affiliation":[{"name":"Antwerp University Hospital, Antwerp, Belgium","place":["Edegem"],"department":["Department of Haematology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Gadisseur","sequence":"additional","affiliation":[{"name":"Antwerp University Hospital, Antwerp, Belgium","place":["Edegem"],"department":["Department of Haematology"]},{"name":"Antwerp University Hospital, Antwerpen, Belgium","place":["Edegem"],"department":["Haemostasis and Thrombosis Research Center"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"issue":"09","key":"ref1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s12032-023-02146-y","article-title":"Revolutionizing cancer treatment: a comprehensive review of CAR-T cell therapy","volume":"40","author":"P Dabas","year":"2023","journal-title":"Med Oncol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"927153","DOI":"10.3389\/fimmu.2022.927153","article-title":"CAR-T cell therapy in hematological malignancies: current opportunities and challenges","volume":"13","author":"X Zhang","year":"2022","journal-title":"Front Immunol"},{"issue":"06","key":"ref3","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1111\/ejh.13851","article-title":"CAR-T cell therapy for patients with hematological malignancies. A systematic review","volume":"109","author":"D M Pasqui","year":"2022","journal-title":"Eur J Haematol"},{"issue":"02","key":"ref4","doi-asserted-by":"crossref","first-page":"194","DOI":"10.3390\/pharmaceutics12020194","article-title":"Chimeric antigen receptor-T-cell therapy for B-cell hematological malignancies: an update of the pivotal clinical trial data","volume":"12","author":"G Roex","year":"2020","journal-title":"Pharmaceutics"},{"issue":"04","key":"ref5","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.bbmt.2018.12.758","article-title":"ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells","volume":"25","author":"D W Lee","year":"2019","journal-title":"Biol Blood Marrow Transplant"},{"issue":"01","key":"ref6","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s12929-023-00982-8","article-title":"Complete spectrum of adverse events associated with chimeric antigen receptor (CAR)-T cell therapies","volume":"30","author":"C Yang","year":"2023","journal-title":"J Biomed Sci"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1396490","DOI":"10.3389\/fonc.2024.1396490","article-title":"Mechanisms and management of CAR T toxicity","volume":"14","author":"C J Ferreri","year":"2024","journal-title":"Front Oncol"},{"issue":"03","key":"ref8","doi-asserted-by":"crossref","first-page":"210","DOI":"10.3343\/alm.2023.0388","article-title":"Current challenges in chimeric antigen receptor T-cell therapy in patients with B-cell lymphoid malignancies","volume":"44","author":"S J Kim","year":"2024","journal-title":"Ann Lab Med"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"950923","DOI":"10.3389\/fphar.2022.950923","article-title":"The pathogenesis, diagnosis, prevention, and treatment of CAR-T cell therapy-related adverse reactions","volume":"13","author":"Y Li","year":"2022","journal-title":"Front Pharmacol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1378944","DOI":"10.3389\/fimmu.2024.1378944","article-title":"Biomarkers for prediction of CAR T therapy outcomes: current and future perspectives","volume":"15","author":"L Levstek","year":"2024","journal-title":"Front Immunol"},{"issue":"09","key":"ref11","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1038\/s41591-024-03084-6","article-title":"A systematic review and meta-analysis of nonrelapse mortality after CAR T cell therapy","volume":"30","author":"D M Cordas Dos Santos","year":"2024","journal-title":"Nat Med"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1699894","DOI":"10.3389\/fimmu.2025.1699894","article-title":"Endothelial dysfunction and hemostatic imbalance in CAR T-cell-associated toxicities: pathophysiological insights and the role of circulating biomarkers","volume":"16","author":"A B Moreno-Casta\u00f1o","year":"2025","journal-title":"Front Immunol"},{"issue":"11","key":"ref13","doi-asserted-by":"crossref","first-page":"3886","DOI":"10.3390\/ijms21113886","article-title":"A new era in endothelial injury syndromes: toxicity of CAR-T cells and the role of immunity","volume":"21","author":"E Gavriilaki","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"12","key":"ref14","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1158\/2159-8290.CD-17-1084","article-title":"CNS endothelial cell activation emerges as a driver of CAR T cell-associated neurotoxicity","volume":"7","author":"C L Mackall","year":"2017","journal-title":"Cancer Discov"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s40364-018-0116-0","article-title":"Biomarkers of cytokine release syndrome and neurotoxicity related to CAR-T cell therapy","volume":"6","author":"Z Wang","year":"2018","journal-title":"Biomark Res"},{"issue":"04","key":"ref16","doi-asserted-by":"crossref","first-page":"e006365","DOI":"10.1136\/jitc-2022-006365","article-title":"Characterization of the endotheliopathy, innate-immune activation and hemostatic imbalance underlying CAR-T cell toxicities: laboratory tools for an early and differential diagnosis","volume":"11","author":"A B Moreno-Casta\u00f1o","year":"2023","journal-title":"J Immunother Cancer"},{"issue":"24","key":"ref17","doi-asserted-by":"crossref","first-page":"11063","DOI":"10.1111\/jcmm.17029","article-title":"Predictive role of endothelial cell activation in cytokine release syndrome after chimeric antigen receptor T cell therapy for acute lymphoblastic leukaemia","volume":"25","author":"F Hong","year":"2021","journal-title":"J Cell Mol Med"},{"issue":"12","key":"ref18","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1158\/2159-8290.CD-17-0698","article-title":"Endothelial activation and blood-brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T cells","volume":"7","author":"J Gust","year":"2017","journal-title":"Cancer Discov"},{"issue":"21","key":"ref19","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1182\/blood-2017-06-793141","article-title":"Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy","volume":"130","author":"K A Hay","year":"2017","journal-title":"Blood"},{"issue":"12","key":"ref20","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1182\/blood-2009-05-199208","article-title":"Coagulation and innate immune responses: can we view them separately?","volume":"114","author":"M Delvaeye","year":"2009","journal-title":"Blood"},{"issue":"06","key":"ref21","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.smim.2016.10.010","article-title":"Blood coagulation in immunothrombosis-at the frontline of intravascular immunity","volume":"28","author":"F Gaertner","year":"2016","journal-title":"Semin Immunol"},{"issue":"09","key":"ref22","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1182\/blood-2018-11-882993","article-title":"Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms","volume":"133","author":"S P Jackson","year":"2019","journal-title":"Blood"},{"issue":"04","key":"ref23","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.3390\/jcm12041399","article-title":"Immunothrombosis: molecular aspects and new therapeutic perspectives","volume":"12","author":"M Marcos-Jubilar","year":"2023","journal-title":"J Clin Med"},{"issue":"01","key":"ref24","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1055\/a-2178-6491","article-title":"The concept of thromboinflammation","volume":"44","author":"W C Schrottmaier","year":"2024","journal-title":"Hamostaseologie"},{"issue":"08","key":"ref25","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1158\/2159-8290.CD-17-1319","article-title":"Clinical and biological correlates of neurotoxicity associated with CAR T-cell therapy in patients with B-cell acute lymphoblastic leukemia","volume":"8","author":"B D Santomasso","year":"2018","journal-title":"Cancer Discov"},{"issue":"22","key":"ref26","doi-asserted-by":"crossref","first-page":"5443","DOI":"10.3390\/cancers15225443","article-title":"Population-based external validation of the EASIX scores to predict CAR T-cell-related toxicities","volume":"15","author":"J W de Boer","year":"2023","journal-title":"Cancers"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"877477","DOI":"10.3389\/fimmu.2022.877477","article-title":"EASIX and severe endothelial complications after CD19-directed CAR-T cell therapy-a cohort study","volume":"13","author":"F Korell","year":"2022","journal-title":"Front Immunol"},{"issue":"10","key":"ref28","doi-asserted-by":"crossref","first-page":"e009220","DOI":"10.1136\/jitc-2024-009220","article-title":"EASIX-guided risk stratification for complications and outcome after CAR T-cell therapy with ide-cel in relapsed\/refractory multiple myeloma","volume":"12","author":"J H Frenking","year":"2024","journal-title":"J Immunother Cancer"},{"issue":"07","key":"ref29","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1111\/j.1538-7836.2005.01328.x","article-title":"Spatial and temporal dynamics of the endothelium","volume":"3","author":"W C Aird","year":"2005","journal-title":"J Thromb Haemost"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1042\/BST0330401","article-title":"Coagulation inhibitors in inflammation","volume":"33","author":"C T Esmon","year":"2005","journal-title":"Biochem Soc Trans"},{"issue":"03","key":"ref31","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1080\/10739680590925493","article-title":"Endogenous mechanisms of inhibition of platelet function","volume":"12","author":"R C Jin","year":"2005","journal-title":"Microcirculation"},{"issue":"01","key":"ref32","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s00281-011-0285-5","article-title":"Endothelium--role in regulation of coagulation and inflammation","volume":"34","author":"V W van Hinsbergh","year":"2012","journal-title":"Semin Immunopathol"},{"issue":"01","key":"ref33","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.htct.2023.05.008","article-title":"Immunothrombosis and its underlying biological mechanisms","volume":"46","author":"A C De Nardi","year":"2024","journal-title":"Hematol Transfus Cell Ther"},{"issue":"01","key":"ref34","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1182\/blood-2004-01-0107","article-title":"Effects of inflammatory cytokines on the release and cleavage of the endothelial cell-derived ultralarge von Willebrand factor multimers under flow","volume":"104","author":"A Bernardo","year":"2004","journal-title":"Blood"},{"issue":"01","key":"ref35","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2991\/chi.k.210117.001","article-title":"The many faces of cytokine release syndrome-related coagulopathy","volume":"3","author":"J Wang","year":"2021","journal-title":"Clin Hematol Int"},{"issue":"01","key":"ref36","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nri3345","article-title":"Thrombosis as an intravascular effector of innate immunity","volume":"13","author":"B Engelmann","year":"2013","journal-title":"Nat Rev Immunol"},{"issue":"02","key":"ref37","first-page":"78","article-title":"New mechanisms in vein thrombosis: Immunothrombosis","volume":"153","author":"J A P\u00e1ramo","year":"2019","journal-title":"Med Clin (Barc)"},{"issue":"09","key":"ref38","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/s41569-021-00552-1","article-title":"Interplay between inflammation and thrombosis in cardiovascular pathology","volume":"18","author":"K Stark","year":"2021","journal-title":"Nat Rev Cardiol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1144229","DOI":"10.3389\/fimmu.2023.1144229","article-title":"Endothelial dysfunction and immunothrombosis in sepsis","volume":"14","author":"E Maneta","year":"2023","journal-title":"Front Immunol"},{"issue":"05","key":"ref40","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41577-021-00536-9","article-title":"Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19","volume":"21","author":"A Bonaventura","year":"2021","journal-title":"Nat Rev Immunol"},{"issue":"10","key":"ref41","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1111\/jth.15830","article-title":"Sustained VWF-ADAMTS-13 axis imbalance and endotheliopathy in long COVID syndrome is related to immune dysfunction","volume":"20","author":"H Fogarty","year":"2022","journal-title":"J Thromb Haemost"},{"key":"ref42","volume-title":"Physiology, Von Willebrand Factor","author":"G A Cortes","year":"2025"},{"issue":"21","key":"ref43","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1056\/NEJMra1601561","article-title":"Von Willebrand\u2019s disease","volume":"375","author":"F W Leebeek","year":"2016","journal-title":"N Engl J Med"},{"issue":"01","key":"ref44","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41572-024-00536-8","article-title":"von Willebrand disease","volume":"10","author":"O Seidizadeh","year":"2024","journal-title":"Nat Rev Dis Primers"},{"issue":"12","key":"ref45","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1182\/blood.2023021915","article-title":"Novel functions for von Willebrand factor","volume":"144","author":"F Atiq","year":"2024","journal-title":"Blood"},{"issue":"12","key":"ref46","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1111\/jth.15873","article-title":"Mechanisms of ADAMTS13 regulation","volume":"20","author":"V DeYoung","year":"2022","journal-title":"J Thromb Haemost"},{"issue":"12","key":"ref47","doi-asserted-by":"crossref","first-page":"3212","DOI":"10.1182\/blood-2011-02-306597","article-title":"Unraveling the scissile bond: how ADAMTS13 recognizes and cleaves von Willebrand factor","volume":"118","author":"J TB Crawley","year":"2011","journal-title":"Blood"},{"issue":"01","key":"ref48","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3324\/haematol.11677","article-title":"Inflammation-associated ADAMTS13 deficiency promotes formation of ultra-large von Willebrand factor","volume":"93","author":"C L Bockmeyer","year":"2008","journal-title":"Haematologica"},{"issue":"02","key":"ref49","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1160\/TH08-03-0161","article-title":"Variations in the ratio between von Willebrand factor and its cleaving protease during systemic inflammation and association with severity and prognosis of organ failure","volume":"101","author":"R A Claus","year":"2009","journal-title":"Thromb Haemost"},{"issue":"02","key":"ref50","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1182\/blood-2018-02-769000","article-title":"Inflammation, von Willebrand factor, and ADAMTS13","volume":"132","author":"J Chen","year":"2018","journal-title":"Blood"},{"issue":"02","key":"ref51","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1111\/jth.13571","article-title":"Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies","volume":"15","author":"M Scully","year":"2017","journal-title":"J Thromb Haemost"},{"issue":"02","key":"ref52","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1097\/SHK.0000000000002291","article-title":"Reviewing the dysregulation of Adamts13 and VWF in sepsis","volume":"61","author":"H Madarati","year":"2024","journal-title":"Shock"},{"issue":"03","key":"ref53","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1111\/jth.14686","article-title":"Von Willebrand factor and ADAMTS13 impact on the outcome of Staphylococcus aureus sepsis","volume":"18","author":"M Peetermans","year":"2020","journal-title":"J Thromb Haemost"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.ijid.2021.06.051","article-title":"Endotheliopathy marked by high von Willebrand factor (VWF) antigen in COVID-19 is associated with poor outcome: a systematic review and meta-analysis","volume":"117","author":"A Wibowo","year":"2022","journal-title":"Int J Infect Dis"},{"issue":"06","key":"ref55","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1038\/s41409-024-02242-1","article-title":"Von Willebrand factor as a potential predictive biomarker of early complications of endothelial origin after allogeneic hematopoietic stem cell transplantation","volume":"59","author":"G Dachy","year":"2024","journal-title":"Bone Marrow Transplant"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"610696","DOI":"10.3389\/fimmu.2020.610696","article-title":"Insights into immunothrombosis: the interplay among neutrophil extracellular trap, von Willebrand factor, and ADAMTS13","volume":"11","author":"J Yang","year":"2020","journal-title":"Front Immunol"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"5620314","DOI":"10.1155\/2017\/5620314","article-title":"The role of von Willebrand factor in vascular inflammation: from pathogenesis to targeted therapy","volume":"2017","author":"F Gragnano","year":"2017","journal-title":"Mediat Inflamm"},{"issue":"07","key":"ref58","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1161\/ATVBAHA.113.303016","article-title":"von Willebrand factor directly interacts with DNA from neutrophil extracellular traps","volume":"34","author":"S Gr\u00e4ssle","year":"2014","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"05","key":"ref59","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1111\/jth.12895","article-title":"NET untangled in TMA?","volume":"13","author":"P Kn\u00f6bl","year":"2015","journal-title":"J Thromb Haemost"},{"issue":"11","key":"ref60","doi-asserted-by":"crossref","first-page":"4150","DOI":"10.1182\/blood-2003-10-3685","article-title":"The Tie-2 ligand angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies","volume":"103","author":"U Fiedler","year":"2004","journal-title":"Blood"},{"issue":"09","key":"ref61","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/nrd.2016.278","article-title":"Therapeutic targeting of the angiopoietin-TIE pathway","volume":"16","author":"P Saharinen","year":"2017","journal-title":"Nat Rev Drug Discov"},{"issue":"06","key":"ref62","doi-asserted-by":"crossref","first-page":"507","DOI":"10.4161\/viru.24530","article-title":"Biomarkers of endothelial activation\/dysfunction in infectious diseases","volume":"4","author":"A V Page","year":"2013","journal-title":"Virulence"},{"issue":"09","key":"ref63","doi-asserted-by":"crossref","first-page":"a006550","DOI":"10.1101\/cshperspect.a006650","article-title":"The complex role of angiopoietin-2 in the angiopoietin-tie signaling pathway","volume":"2","author":"G Thurston","year":"2012","journal-title":"Cold Spring Harb Perspect Med"},{"issue":"16","key":"ref64","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1101\/gad.8.16.1897","article-title":"Dominant-negative and targeted null mutations in the endothelial receptor tyrosine kinase, tek, reveal a critical role in vasculogenesis of the embryo","volume":"8","author":"D J Dumont","year":"1994","journal-title":"Genes Dev"},{"issue":"6535","key":"ref65","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/376070a0","article-title":"Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation","volume":"376","author":"T N Sato","year":"1995","journal-title":"Nature"},{"issue":"03","key":"ref66","doi-asserted-by":"crossref","first-page":"e46","DOI":"10.1371\/journal.pmed.0030046","article-title":"Excess circulating angiopoietin-2 may contribute to pulmonary vascular leak in sepsis in humans","volume":"3","author":"S M Parikh","year":"2006","journal-title":"PLoS Med"},{"issue":"11","key":"ref67","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1097\/CCM.0b013e31825fdc31","article-title":"Angiopoietin-2 may contribute to multiple organ dysfunction and death in sepsis*","volume":"40","author":"S David","year":"2012","journal-title":"Crit Care Med"},{"issue":"09","key":"ref68","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1007\/s00134-009-1560-y","article-title":"Circulating angiopoietin-2 levels in the course of septic shock: relation with fluid balance, pulmonary dysfunction and mortality","volume":"35","author":"M van der Heijden","year":"2009","journal-title":"Intensive Care Med"},{"issue":"02","key":"ref69","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1182\/blood-2018-01-769018","article-title":"von Willebrand factor regulation of blood vessel formation","volume":"132","author":"A M Randi","year":"2018","journal-title":"Blood"},{"issue":"01","key":"ref70","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1160\/TH17-06-0397","article-title":"Circulating angiogenic mediators in patients with moderate and severe von Willebrand disease: a multicentre cross-sectional study","volume":"118","author":"D J Groeneveld","year":"2018","journal-title":"Thromb Haemost"},{"issue":"21","key":"ref71","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1182\/blood.2025031558","article-title":"Von Willebrand factor deficiency impairs angiogenesis via angiopoietin-2: relevance for gut angiodysplasia","volume":"147","author":"A Constantinescu-Bercu","year":"2026","journal-title":"Blood"},{"issue":"19","key":"ref72","doi-asserted-by":"crossref","first-page":"6124","DOI":"10.3390\/jcm12196124","article-title":"Exploring CAR-T cell therapy side effects: mechanisms and management strategies","volume":"12","author":"Y Zhang","year":"2023","journal-title":"J Clin Med"},{"issue":"07","key":"ref73","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/s41571-024-00903-0","article-title":"Current understanding and management of CAR T cell-associated toxicities","volume":"21","author":"J N Brudno","year":"2024","journal-title":"Nat Rev Clin Oncol"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"1422591","DOI":"10.3389\/fimmu.2024.1422591","article-title":"Systemic toxicity of CAR-T therapy and potential monitoring indicators for toxicity prevention","volume":"15","author":"J Li","year":"2024","journal-title":"Front Immunol"},{"key":"ref75","doi-asserted-by":"crossref","first-page":"618387","DOI":"10.3389\/fimmu.2020.618387","article-title":"Befriending the hostile tumor microenvironment in CAR T-cell therapy","volume":"11","author":"L Lindo","year":"2021","journal-title":"Front Immunol"},{"issue":"02","key":"ref76","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1182\/blood-2014-05-552729","article-title":"Current concepts in the diagnosis and management of cytokine release syndrome","volume":"124","author":"D W Lee","year":"2014","journal-title":"Blood"},{"issue":"01","key":"ref77","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nrclinonc.2017.148","article-title":"Chimeric antigen receptor T-cell therapy - assessment and management of toxicities","volume":"15","author":"S S Neelapu","year":"2018","journal-title":"Nat Rev Clin Oncol"},{"issue":"01","key":"ref78","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1186\/s13046-021-02148-6","article-title":"Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies","volume":"40","author":"X Xiao","year":"2021","journal-title":"J Exp Clin Cancer Res"},{"issue":"07","key":"ref79","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1111\/j.1538-7836.2008.02989.x","article-title":"Inflammatory cytokines inhibit ADAMTS13 synthesis in hepatic stellate cells and endothelial cells","volume":"6","author":"W J Cao","year":"2008","journal-title":"J Thromb Haemost"},{"issue":"01","key":"ref80","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12964-018-0268-4","article-title":"Activation of the JAK\/STAT3 and PI3K\/AKT pathways are crucial for IL-6 trans-signaling-mediated pro-inflammatory response in human vascular endothelial cells","volume":"16","author":"M M Zegeye","year":"2018","journal-title":"Cell Commun Signal"},{"issue":"17","key":"ref81","doi-asserted-by":"crossref","first-page":"2876","DOI":"10.3390\/cancers17172876","article-title":"Endothelial injury following CAR-T cell immunotherapy for hematological malignancies","volume":"17","author":"C Demosthenous","year":"2025","journal-title":"Cancers"},{"key":"ref82","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.blre.2018.11.002","article-title":"Recent advances in CAR T-cell toxicity: mechanisms, manifestations and management","volume":"34","author":"J N Brudno","year":"2019","journal-title":"Blood Rev"},{"issue":"06","key":"ref83","doi-asserted-by":"crossref","first-page":"e1576","DOI":"10.1002\/wsbm.1576","article-title":"Mechanisms of immune effector cell-associated neurotoxicity syndrome after CAR-T treatment","volume":"14","author":"T Gu","year":"2022","journal-title":"WIREs Mech Dis"},{"issue":"01","key":"ref84","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s12967-025-07646-1","article-title":"Immune effector cell-associated neurotoxicity syndrome following CAR T-cell therapy: a review of recent advances","volume":"24","author":"M Fatahichegeni","year":"2025","journal-title":"J Transl Med"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"1108297","DOI":"10.3389\/fneur.2023.1108297","article-title":"Novel pathophysiological insights into CAR-T cell associated neurotoxicity","volume":"14","author":"V Genoud","year":"2023","journal-title":"Front Neurol"},{"issue":"01","key":"ref86","doi-asserted-by":"crossref","first-page":"644","DOI":"10.3390\/ijms25010644","article-title":"The mechanisms of altered blood-brain barrier permeability in CD19 CAR T-cell recipients","volume":"25","author":"S N Pinto","year":"2024","journal-title":"Int J Mol Sci"},{"key":"ref87","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1182\/blood-2025-2339","article-title":"Pre-infusion ADAMTS13 and VWF levels are associated with clinical outcomes of patients receiving CAR-T cell therapy","volume":"146","author":"A Shoaib","year":"2025","journal-title":"Blood"},{"issue":"06","key":"ref88","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1158\/2159-8290.CD-16-0040","article-title":"Identification of predictive biomarkers for cytokine release syndrome after chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia","volume":"6","author":"D T Teachey","year":"2016","journal-title":"Cancer Discov"},{"issue":"06","key":"ref89","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/s41591-018-0036-4","article-title":"Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells","volume":"24","author":"M Norelli","year":"2018","journal-title":"Nat Med"},{"issue":"20","key":"ref90","first-page":"2430","article-title":"How I treat refractory CRS and ICANS after CAR T-cell therapy","volume":"141","author":"M D Jain","year":"2023","journal-title":"Blood"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"1273507","DOI":"10.3389\/fimmu.2023.1273507","article-title":"Prediction of severe CRS and determination of biomarkers in B cell-acute lymphoblastic leukemia treated with CAR-T cells","volume":"14","author":"Z Wei","year":"2023","journal-title":"Front Immunol"},{"issue":"22","key":"ref92","doi-asserted-by":"crossref","first-page":"5898","DOI":"10.1182\/bloodadvances.2022007381","article-title":"Dynamic EASIX scores closely predict nonrelapse mortality after allogeneic hematopoietic cell transplantation","volume":"6","author":"M T Nawas","year":"2022","journal-title":"Blood Adv"},{"issue":"01","key":"ref93","doi-asserted-by":"crossref","first-page":"e007635","DOI":"10.1136\/jitc-2023-007635","article-title":"Endothelial activation and stress index (EASIX) to predict mortality after allogeneic stem cell transplantation: a prospective study","volume":"12","author":"O Penack","year":"2024","journal-title":"J Immunother Cancer"},{"issue":"03","key":"ref94","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/s41409-024-02489-8","article-title":"The EASIX score as a predictor of sinusoidal obstruction syndrome and nonrelapse mortality in paediatric patients receiving allogeneic haematopoietic stem cell transplantation","volume":"60","author":"E Muratore","year":"2025","journal-title":"Bone Marrow Transplant"},{"issue":"09","key":"ref95","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1038\/sj.bmt.1701211","article-title":"Hepatic veno-occlusive disease with severe capillary leakage after peripheral stem cell transplantation: treatment with recombinant plasminogen activator and C1-esterase inhibitor concentrate","volume":"21","author":"R Heying","year":"1998","journal-title":"Bone Marrow Transplant"},{"issue":"12","key":"ref96","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1038\/bmt.2011.65","article-title":"The role of the endothelium in the short-term complications of hematopoietic SCT","volume":"46","author":"E Carreras","year":"2011","journal-title":"Bone Marrow Transplant"},{"issue":"07","key":"ref97","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/ajh.20648","article-title":"Risk factor analysis for thrombotic microangiopathy after reduced-intensity or myeloablative allogeneic hematopoietic stem cell transplantation","volume":"81","author":"H Nakamae","year":"2006","journal-title":"Am J Hematol"},{"issue":"06","key":"ref98","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/s41409-025-02567-5","article-title":"Less frequent complications following CAR T-cell therapies: hemophagocytic lymphohistiocytosis, graft-versus-host disease, thrombotic microangiopathy, coagulation disorders and secondary malignancies: best practice recommendations from the EBMT practice harmonization and guidelines committee","volume":"60","author":"G Ort\u00ed","year":"2025","journal-title":"Bone Marrow Transplant"},{"issue":"01","key":"ref100","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1111\/bjh.18596","article-title":"Endothelial activation predicts disseminated intravascular coagulopathy, cytokine release syndrome and prognosis in patients treated with anti-CD19 CAR-T cells","volume":"201","author":"E Galli","year":"2023","journal-title":"Br J Haematol"},{"issue":"03","key":"ref101","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1007\/s00277-024-05617-y","article-title":"Modified EASIX scores predict severe CRS\/ICANS in patients with acute myeloid leukemia following CLL1 CAR-T cell therapy","volume":"103","author":"Y Zhao","year":"2024","journal-title":"Ann Hematol"},{"issue":"02","key":"ref102","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1182\/bloodadvances.2024014027","article-title":"EASIX and m-EASIX predict CRS and ICANS in pediatric and AYA patients after CD19-CAR T-cell therapy","volume":"9","author":"D Zandaki","year":"2025","journal-title":"Blood Adv"},{"issue":"01","key":"ref103","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/ana.25502","article-title":"Glial injury in neurotoxicity after pediatric CD19-directed chimeric antigen receptor T cell therapy","volume":"86","author":"J Gust","year":"2019","journal-title":"Ann Neurol"},{"issue":"05","key":"ref104","doi-asserted-by":"crossref","first-page":"e1049","DOI":"10.1002\/cti2.1049","article-title":"Selecting costimulatory domains for chimeric antigen receptors: functional and clinical considerations","volume":"8","author":"R Weinkove","year":"2019","journal-title":"Clin Transl Immunol"},{"issue":"07","key":"ref105","doi-asserted-by":"crossref","first-page":"115973","DOI":"10.1016\/j.celrep.2025.115973","article-title":"CAR-T cells containing CD28 versus 4-1BB co-stimulatory domains show distinct metabolic profiles in patients","volume":"44","author":"M S Cook","year":"2025","journal-title":"Cell Rep"},{"issue":"11","key":"ref106","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/s41571-021-00530-z","article-title":"A comparison of chimeric antigen receptors containing CD28 versus 4-1BB costimulatory domains","volume":"18","author":"K M Cappell","year":"2021","journal-title":"Nat Rev Clin Oncol"},{"issue":"05","key":"ref107","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.bbmt.2019.11.027","article-title":"Coagulation disorders after chimeric antigen receptor T cell therapy: analysis of 100 patients with relapsed and refractory hematologic malignancies","volume":"26","author":"Y Wang","year":"2020","journal-title":"Biol Blood Marrow Transplant"},{"issue":"07","key":"ref108","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1038\/s41409-021-01226-9","article-title":"CRS-related coagulopathy in BCMA targeted CAR-T therapy: a retrospective analysis in a phase I\/II clinical trial","volume":"56","author":"M Shao","year":"2021","journal-title":"Bone Marrow Transplant"},{"issue":"07","key":"ref109","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1007\/s00277-019-03685-z","article-title":"Improving the safety of CAR-T cell therapy by controlling CRS-related coagulopathy","volume":"98","author":"H Jiang","year":"2019","journal-title":"Ann Hematol"},{"issue":"18","key":"ref110","doi-asserted-by":"crossref","first-page":"975","DOI":"10.21037\/atm-22-3814","article-title":"The correlation factors and prognostic significance of coagulation disorders after chimeric antigen receptor T cell therapy in hematological malignancies: a cohort study","volume":"10","author":"R Dong","year":"2022","journal-title":"Ann Transl Med"},{"issue":"02","key":"ref111","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1111\/bjh.19583","article-title":"Coagulation abnormalities associated with CAR-T-cell therapy in haematological malignancies: a review","volume":"205","author":"X Peng","year":"2024","journal-title":"Br J Haematol"},{"issue":"02","key":"ref112","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1182\/bloodadvances.2020002757","article-title":"Practical guidelines for monitoring and management of coagulopathy following tisagenlecleucel CAR T-cell therapy","volume":"5","author":"J Buechner","year":"2021","journal-title":"Blood Adv"},{"issue":"21","key":"ref113","doi-asserted-by":"crossref","first-page":"4465","DOI":"10.1182\/bloodadvances.2021004716","article-title":"Incidence and risk factors associated with bleeding and thrombosis following chimeric antigen receptor T-cell therapy","volume":"5","author":"A Johnsrud","year":"2021","journal-title":"Blood Adv"},{"issue":"06","key":"ref114","doi-asserted-by":"crossref","first-page":"e005898","DOI":"10.1136\/jitc-2022-005898","article-title":"CD22 CAR T-cell associated hematologic toxicities, endothelial activation and relationship to neurotoxicity","volume":"11","author":"J Jess","year":"2023","journal-title":"J Immunother Cancer"},{"issue":"16","key":"ref115","doi-asserted-by":"crossref","first-page":"4348","DOI":"10.1182\/bloodadvances.2024013044","article-title":"CAR T-cell toxicities: from bedside to bench, how novel toxicities inform laboratory investigations","volume":"8","author":"F Perna","year":"2024","journal-title":"Blood Adv"},{"issue":"07","key":"ref116","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1016\/j.jtha.2024.03.021","article-title":"A meta-analysis to assess the risk of bleeding and thrombosis following chimeric antigen receptor T-cell therapy: communication from the ISTH SSC subcommittee on Hemostasis and malignancy","volume":"22","author":"P Bindal","year":"2024","journal-title":"J Thromb Haemost"},{"issue":"17","key":"ref117","doi-asserted-by":"crossref","first-page":"4086","DOI":"10.1182\/bloodadvances.2020002060","article-title":"Venous thromboembolism associated with CD19-directed CAR T-cell therapy in large B-cell lymphoma","volume":"4","author":"H Hashmi","year":"2020","journal-title":"Blood Adv"},{"issue":"04","key":"ref118","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1080\/10428194.2020.1852474","article-title":"Incidence, management and outcomes of arterial and venous thrombosis after chimeric antigen receptor modified T cells for B cell lymphoma and multiple myeloma","volume":"62","author":"A L Parks","year":"2021","journal-title":"Leuk Lymphoma"},{"issue":"09","key":"ref119","doi-asserted-by":"crossref","first-page":"8349","DOI":"10.3390\/ijms24098349","article-title":"Thrombotic events are unusual toxicities of chimeric antigen receptor T-cell therapies","volume":"24","author":"C Schorr","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"14","key":"ref120","doi-asserted-by":"crossref","first-page":"4216","DOI":"10.1182\/bloodadvances.2022007454","article-title":"Relative hypercoagulation induced by suppressed fibrinolysis after tisagenlecleucel infusion in malignant lymphoma","volume":"6","author":"M Yamasaki-Morita","year":"2022","journal-title":"Blood Adv"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"5547","DOI":"10.1182\/blood-2023-187713","article-title":"Risk of bleeding and thrombosis with CAR T-cell therapy: a scoping review","volume":"142","author":"M Abufarhaneh","year":"2023","journal-title":"Blood"},{"issue":"01","key":"ref122","first-page":"63","article-title":"TNF-\u03b1 increases the risk of bleeding in patients after CAR T-cell therapy: a bleeding model based on a real-world study of Chinese CAR T working party","volume":"40","author":"J Qi","year":"2022","journal-title":"Hematol Oncol"},{"key":"ref123","doi-asserted-by":"publisher","DOI":"10.4081\/btvb.2026.461","article-title":"Bleeding and thrombosis in patients receiving chimeric antigen receptor T-cell therapy","author":"D Lee","year":"2026","journal-title":"Bleeding Thromb Vasc Biol"},{"issue":"16","key":"ref124","first-page":"e24085","article-title":"Incidence and risk factors for venous thromboembolism after CAR T-cell therapy: a systematic review and meta-analysis","volume":"43","author":"A Bailey","year":"2025","journal-title":"J Clin Oncol"},{"key":"ref125","doi-asserted-by":"crossref","first-page":"4496","DOI":"10.1182\/blood-2025-4496","article-title":"Incidence of thrombosis and bleeding in patients receiving CAR-T cell therapy: a multicentric retrospective analysis of the Canadian experience","volume":"146","author":"L Melo Garcia","year":"2025","journal-title":"Blood"},{"issue":"02","key":"ref126","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/bjh.19619","article-title":"Coagulopathy in CAR-T: critical concern or mere blip?","volume":"205","author":"E Galli","year":"2024","journal-title":"Br J Haematol"},{"issue":"03","key":"ref127","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jtct.2022.11.015","article-title":"Harmonizing definitions for diagnostic criteria and prognostic assessment of transplantation-associated thrombotic microangiopathy: a report on behalf of the European Society for Blood and Marrow Transplantation, American Society for Transplantation and Cellular Therapy, Asia-Pacific blood and marrow transplantation group, and Center for International Blood and Marrow Transplant Research","volume":"29","author":"M L Schoettler","year":"2023","journal-title":"Transplant Cell Ther"},{"issue":"06","key":"ref128","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/s41591-018-0041-7","article-title":"CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade","volume":"24","author":"T Giavridis","year":"2018","journal-title":"Nat Med"},{"issue":"02","key":"ref129","first-page":"S247","article-title":"The effect of statin use on outcome in patients receiving chimeric antigen receptor T-cell therapy. Transplantation and cellular therapy","volume":"31","author":"S L Yu","year":"2025","journal-title":"Off Publ Am Soc Transplant Cell Therap"},{"issue":"21","key":"ref130","doi-asserted-by":"crossref","first-page":"6790","DOI":"10.1182\/bloodadvances.2023009961","article-title":"A phase 2 trial of defibrotide for the prevention of chimeric antigen receptor T-cell-associated neurotoxicity syndrome","volume":"7","author":"C A Jacobson","year":"2023","journal-title":"Blood Adv"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"623610","DOI":"10.3389\/fimmu.2021.623610","article-title":"Therapeutic potential of TNF\u03b1 and IL1\u03b2 blockade for CRS\/ICANS in CAR-T therapy via ameliorating endothelial activation","volume":"12","author":"Y Chen","year":"2021","journal-title":"Front Immunol"},{"issue":"02","key":"ref132","doi-asserted-by":"crossref","first-page":"S247","DOI":"10.1016\/j.jtct.2025.01.376","article-title":"The effect of statin use on outcome in patients receiving chimeric antigen receptor T-cell therapy","volume":"31","author":"L Y Stephen","year":"2025","journal-title":"Transplant Cell Ther."},{"issue":"18","key":"ref133","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1056\/NEJMoa2402567","article-title":"Recombinant ADAMTS13 for immune thrombotic thrombocytopenic purpura","volume":"390","author":"P K Bendapudi","year":"2024","journal-title":"N Engl J Med"},{"issue":"04","key":"ref134","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1056\/NEJMoa1806311","article-title":"Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura","volume":"380","author":"M Scully","year":"2019","journal-title":"N Engl J Med"},{"key":"ref135","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.thromres.2021.02.012","article-title":"Recombinant ADAMTS13 reduces abnormally up-regulated von Willebrand factor in plasma from patients with severe COVID-19","volume":"201","author":"P L Turecek","year":"2021","journal-title":"Thromb Res"},{"issue":"06","key":"ref136","doi-asserted-by":"crossref","first-page":"572","DOI":"10.4161\/viru.25740","article-title":"Emerging therapeutic strategies to prevent infection-related microvascular endothelial activation and dysfunction","volume":"4","author":"I Darwish","year":"2013","journal-title":"Virulence"},{"issue":"11","key":"ref137","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1038\/ki.2009.387","article-title":"COMP-angiopoietin-1 decreases lipopolysaccharide-induced acute kidney injury","volume":"76","author":"D H Kim","year":"2009","journal-title":"Kidney Int"},{"issue":"10","key":"ref138","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1164\/rccm.200609-1370OC","article-title":"Cell-based angiopoietin-1 gene therapy for acute lung injury","volume":"175","author":"S D McCarter","year":"2007","journal-title":"Am J Respir Crit Care Med"},{"issue":"01","key":"ref139","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1161\/01.CIR.0000151287.08202.8E","article-title":"Protective role of angiopoietin-1 in endotoxic shock","volume":"111","author":"B Witzenbichler","year":"2005","journal-title":"Circulation"},{"issue":"05","key":"ref140","doi-asserted-by":"crossref","first-page":"R261","DOI":"10.1186\/cc10523","article-title":"The synthetic Tie2 agonist peptide vasculotide protects against vascular leakage and reduces mortality in murine abdominal sepsis","volume":"15","author":"P Kumpers","year":"2011","journal-title":"Crit Care"},{"issue":"06","key":"ref141","doi-asserted-by":"crossref","first-page":"L851","DOI":"10.1152\/ajplung.00459.2010","article-title":"Effects of a synthetic PEG-ylated Tie-2 agonist peptide on endotoxemic lung injury and mortality","volume":"300","author":"S David","year":"2011","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"05","key":"ref142","doi-asserted-by":"crossref","first-page":"R182","DOI":"10.1186\/cc11666","article-title":"Angiopoietin-1 variant reduces LPS-induced microvascular dysfunction in a murine model of sepsis","volume":"16","author":"A Alfieri","year":"2012","journal-title":"Crit Care"}],"container-title":["TH Open"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2923-1208.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:49:12Z","timestamp":1786495752000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2923-1208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":141,"journal-issue":{"issue":"CP","published-online":{"date-parts":[[2026,1,9]]},"published-print":{"date-parts":[[2026]]}},"alternative-id":["a29231208"],"URL":"https:\/\/doi.org\/10.1055\/a-2923-1208","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["2512-9465"],"issn-type":[{"value":"2512-9465","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,7,24]]},"published":{"date-parts":[[2026,7,24]]}}}