{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:19:04Z","timestamp":1787822344887,"version":"build-2784847793"},"reference-count":31,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Clinical and Biological Sciences, University of Torino, Torino, Italy, with \u201cRicerca Locale\u201d","award":["PAGP_RILO_24_01"],"award-info":[{"award-number":["PAGP_RILO_24_01"]}]},{"name":"Department of Clinical and Biological Sciences, University of Torino, Torino, Italy, with \u201cRicerca Locale\u201d","award":["SCIS_RILO_24_01"],"award-info":[{"award-number":["SCIS_RILO_24_01"]}]},{"name":"Department of Clinical and Biological Sciences, University of Torino, Torino, Italy, with \u201cRicerca Locale\u201d","award":["MAND_RILO_24_01"],"award-info":[{"award-number":["MAND_RILO_24_01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Antiphospholipid syndrome is a systemic autoimmune disease characterized by elevated circulating antiphospholipid antibodies and a predisposition to recurrent venous and arterial thrombosis. The underlying pathophysiology of antiphospholipid syndrome remains under active investigation, with endothelial dysfunction recognized as a key contributor to vascular complications. In this study, we showed that serum from antiphospholipid syndrome patients differentially affects distinct endothelial cell types, leading to variations in migration and angiogenic behavior. Using human umbilical vein endothelial cells and human microvascular endothelial cells, we assessed the biological response to serum exposure. Treatment with antiphospholipid syndrome serum was associated with an enhanced angiogenic phenotype in venous endothelium, with a significant increase in two of the four tubulogenesis parameters assessed and a trend towards increased migration, while microvascular endothelium remained largely unaffected. Consistently, metalloproteinase-9 activity was upregulated, with these effects being more pronounced in venous compared to microvascular endothelium. Moreover, caspase-3 activity remained unchanged, suggesting that caspase-3-dependent apoptosis is unlikely to be a major contributor to the endothelial response observed under these conditions. These results enhance our understanding of the pathogenesis and highlight the distinct endothelial responses to the antiphospholipid environment. Further investigation into the underlying mechanisms may facilitate the development of targeted therapeutic strategies to mitigate vascular complications.<\/jats:p>","DOI":"10.3390\/biology15171460","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T08:02:27Z","timestamp":1787817747000},"page":"1460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum from Patients with Antiphospholipid Syndrome Differentially Affects Venous and Microcirculatory Endothelial Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3809-6047","authenticated-orcid":false,"given":"Daniele","family":"Mancardi","sequence":"first","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Torino, 10043 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco Maximillian Anthony","family":"Shelton Agar","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Torino, 10043 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4386-1383","authenticated-orcid":false,"given":"Pasquale","family":"Pagliaro","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Torino, 10043 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Marinotti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Torino, 10043 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Arrigo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Torino, 10043 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Barinotti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Torino, 10043 Torino, Italy"},{"name":"Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-Net, ERN-Reconnect and RITA-ERN Member), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hub Hospital, 10154 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1858-5452","authenticated-orcid":false,"given":"Irene","family":"Cecchi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Torino, 10043 Torino, Italy"},{"name":"Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-Net, ERN-Reconnect and RITA-ERN Member), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hub Hospital, 10154 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1941-2606","authenticated-orcid":false,"given":"Massimo","family":"Radin","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Torino, 10043 Torino, Italy"},{"name":"Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-Net, ERN-Reconnect and RITA-ERN Member), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hub Hospital, 10154 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7455-2305","authenticated-orcid":false,"given":"Silvia Grazietta","family":"Foddai","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Torino, 10043 Torino, Italy"},{"name":"Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-Net, ERN-Reconnect and RITA-ERN Member), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hub Hospital, 10154 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4419-6813","authenticated-orcid":false,"given":"Dario","family":"Roccatello","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Torino, 10043 Torino, Italy"},{"name":"Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-Net, ERN-Reconnect and RITA-ERN Member), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hub Hospital, 10154 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1266-9441","authenticated-orcid":false,"given":"Savino","family":"Sciascia","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Torino, 10043 Torino, Italy"},{"name":"Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-Net, ERN-Reconnect and RITA-ERN Member), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hub Hospital, 10154 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Radic, M., and Pattanaik, D. (2018). Cellular and Molecular Mechanisms of Anti-Phospholipid Syndrome. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00969"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.thromres.2020.10.010","article-title":"Thrombotic Antiphospholipid Syndrome: A Practical Guide to Diagnosis and Management","volume":"198","author":"Sayar","year":"2021","journal-title":"Thromb. Res."},{"key":"ref_3","first-page":"20","article-title":"Diagnosis and Classification of the Antiphospholipid Syndrome","volume":"48\u201349","author":"Cervera","year":"2014","journal-title":"J. Autoimmun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1055\/s-0036-1597286","article-title":"New Insights in the Pathophysiology of Antiphospholipid Syndrome","volume":"44","author":"Sacharidou","year":"2018","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s00281-022-00916-w","article-title":"Mechanisms of Immunothrombosis and Vasculopathy in Antiphospholipid Syndrome","volume":"44","author":"Knight","year":"2022","journal-title":"Semin. Immunopathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s13317-011-0017-9","article-title":"Pathophysiology of the Antiphospholipid Antibody Syndrome","volume":"2","author":"Willis","year":"2011","journal-title":"Autoimmun. Highlights"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.blre.2007.09.001","article-title":"Current Insight into Diagnostics and Pathophysiology of the Antiphospolipid Syndrome","volume":"22","author":"Urbanus","year":"2008","journal-title":"Blood Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/nrrheum.2017.124","article-title":"Diagnosing Antiphospholipid Syndrome: \u201cextra-Criteria\u201d Manifestations and Technical Advances","volume":"13","author":"Sciascia","year":"2017","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1007\/s11926-000-0087-6","article-title":"Antiphospholipid Antibodies and the Endothelium","volume":"2","author":"Hunt","year":"2000","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1177\/0961203320950477","article-title":"Antiphospholipid Syndrome (APS) in Patients with Systemic Lupus Erythematosus (SLE) Implies a More Severe Disease with More Damage Accrual and Higher Mortality","volume":"29","author":"Alonso","year":"2020","journal-title":"Lupus"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Vel\u00e1squez, M., Rojas, M., Abrahams, V.M., Escudero, C., and Cadavid, \u00c1.P. (2018). Mechanisms of Endothelial Dysfunction in Antiphospholipid Syndrome: Association with Clinical Manifestations. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.01840"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1161\/01.CIR.99.15.1997","article-title":"Antiphospholipid Antibodies from Antiphospholipid Syndrome Patients Activate Endothelial Cells In Vitro and In Vivo","volume":"99","author":"Pierangeli","year":"1999","journal-title":"Circulation"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1093\/intimm\/dxh229","article-title":"Role of Reactive Oxygen Species and P38 MAPK in the Induction of the Pro-Adhesive Endothelial State Mediated by IgG from Patients with Anti-Phospholipid Syndrome","volume":"17","author":"Simoncini","year":"2005","journal-title":"Int. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez, C.M., Vel\u00e1squez-Berr\u00edo, M., R\u00faa, C., Viana, M., Abrahams, V.M., Cadavid, A.P., and Alvarez, A.M. (2021). Antiphospholipid Antibodies from Women with Pregnancy Morbidity and Vascular Thrombosis Induce Endothelial Mitochondrial Dysfunction, MTOR Activation, and Autophagy. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.706743"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Vel\u00e1squez, M., Pel\u00e1ez, L.F., Rojas, M., Narv\u00e1ez-S\u00e1nchez, R., Vel\u00e1squez, J.A., Escudero, C., San Mart\u00edn, S., and Cadavid, \u00c1.P. (2021). Differences in Endothelial Activation and Dysfunction Induced by Antiphospholipid Antibodies Among Groups of Patients with Thrombotic, Refractory, and Non-Refractory Antiphospholipid Syndrome. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.764702"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jaut.2009.07.004","article-title":"Patients with Antiphospholipid Syndrome Display Endothelial Perturbation","volume":"34","author":"Cugno","year":"2010","journal-title":"J. Autoimmun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nrm3176","article-title":"Molecular Control of Endothelial Cell Behaviour during Blood Vessel Morphogenesis","volume":"12","author":"Herbert","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Rahat, M.A., Kzhyshkowska, J., and Iragavarapu-Charyulu, V. (2020). Editorial: Targeting Angiogenesis to Treat Autoimmune Diseases and Cancer. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01005"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Silva, F., Pad\u00edn-Iruegas, M., Caponio, V., Lorenzo-Pouso, A., Saavedra-Nieves, P., Chamorro-Petronacci, C., Suar\u00e9z-Pe\u00f1aranda, J., and P\u00e9rez-Say\u00e1ns, M. (2022). Caspase 3 and Cleaved Caspase 3 Expression in Tumorogenesis and Its Correlations with Prognosis in Head and Neck Cancer: A Systematic Review and Meta-Analysis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911937"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.2147\/JIR.S275595","article-title":"Reactive Oxygen Species: Drivers of Physiological and Pathological Processes","volume":"13","author":"Checa","year":"2020","journal-title":"J. Inflamm. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1183\/09031936.00146510","article-title":"Biological Role of Matrix Metalloproteinases: A Critical Balance","volume":"38","author":"Schilling","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Tossetta, G., Piani, F., Borghi, C., and Marzioni, D. (2023). Role of CD93 in Health and Disease. Cells, 12.","DOI":"10.3390\/cells12131778"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5859","DOI":"10.1182\/blood-2011-12-400986","article-title":"Mitochondrial Dysfunction in Antiphospholipid Syndrome: Implications in the Pathogenesis of the Disease and Effects of Coenzyme Q(10) Treatment","volume":"119","author":"Aguirre","year":"2012","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/s41392-023-01503-7","article-title":"The Mitophagy Pathway and Its Implications in Human Diseases","volume":"8","author":"Wang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/bs.apha.2017.08.002","article-title":"Matrix Metalloproteinases, Vascular Remodeling, and Vascular Disease","volume":"81","author":"Wang","year":"2018","journal-title":"Adv. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"50446","DOI":"10.1074\/jbc.M409221200","article-title":"P38 Mitogen-Activated Protein Kinase Regulation of Endothelial Cell Migration Depends on Urokinase Plasminogen Activator Expression","volume":"279","author":"Yu","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Dayang, E.-Z., Plantinga, J., ter Ellen, B., van Meurs, M., Molema, G., and Moser, J. (2019). Identification of LPS-Activated Endothelial Subpopulations with Distinct Inflammatory Phenotypes and Regulatory Signaling Mechanisms. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01169"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1902\/jop.2012.120453","article-title":"Comparative Studies on Microvascular Endothelial Cells Isolated from Periodontal Tissue","volume":"84","author":"Suphasiriroj","year":"2012","journal-title":"J. Periodontol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1111\/jth.15417","article-title":"Effect of Heparanase Inhibitor on Tissue Factor Overexpression in Platelets and Endothelial Cells Induced by Anti-\u03b22-GPI Antibodies","volume":"19","author":"Capozzi","year":"2021","journal-title":"J. Thromb. Haemost."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1172\/JCI118276","article-title":"Activation of Cultured Vascular Endothelial Cells by Antiphospholipid Antibodies","volume":"96","author":"Simantov","year":"1995","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Nocella, C., Bartimoccia, S., Cammisotto, V., D\u2019Amico, A., Pastori, D., Frati, G., Sciarretta, S., Rosa, P., Felici, C., and Riggio, O. (2021). Oxidative Stress in the Pathogenesis of Antiphospholipid Syndrome: Implications for the Atherothrombotic Process. Antioxidants, 10.","DOI":"10.3390\/antiox10111790"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/17\/1460\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T08:28:34Z","timestamp":1787819314000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/17\/1460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,27]]},"references-count":31,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["biology15171460"],"URL":"https:\/\/doi.org\/10.3390\/biology15171460","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,27]]}}}