{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T03:23:39Z","timestamp":1787801019277,"version":"build-2784847793"},"reference-count":77,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CIC-UMSNH","award":["320085"],"award-info":[{"award-number":["320085"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>COVID-19 has been associated with an active immunothrombotic process. The involvement of endothelial cells (ECs) in the feedback loop of the inflammatory and thrombotic process characteristic of COVID-19, as well as its differences with other infectious inflammatory conditions, remains an area requiring further elucidation. This study aimed to assess the immunothrombotic phenotype induced by the SARS-CoV-2 Spike (S) protein and its receptor-binding domain (RBD) in endothelial-derived cell lines. HUVEC and EA.hy926 cell lines were exposed to S protein and to its RBD. Inflammatory, thrombotic, and fibrinolytic mediators were quantified. Molecular docking assays were conducted to identify potential EC receptors for S protein. EC activation was dependent on both protein concentration and stimulation time. An increased release of immunothrombotic biomarkers were observed in endothelial-derived cells exposed to the S protein and to its RBD. The RBD induced a stronger endothelial response. Molecular docking demonstrated high affinity and a possible interaction between the S protein and endothelial receptors: CD-141, CD-147, IL-6R, TLR 2, 4, and 7. These findings confirm that the S protein and its RBD can induce an immunothrombotic phenotype in EC-derived cell lines, potentially exacerbating the disease pathology. We propose possible endothelial receptors mediating this response.<\/jats:p>","DOI":"10.3390\/cimb48020161","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T09:48:08Z","timestamp":1770025688000},"page":"161","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Endothelial Cell Activation by SARS-CoV-2 Spike Protein and Its RBD: Central Player of the Immunothrobotic Response in COVID-19"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8620-0962","authenticated-orcid":false,"given":"Alan","family":"Cano-Mendez","sequence":"first","affiliation":[{"name":"Laboratorio de Hemostasia y Biolog\u00eda Vascular, Divisi\u00f3n de Estudios de Posgrado, Facultad de Ciencias M\u00e9dicas y Biol\u00f3gicas \u201cDr. Ignacio Ch\u00e1vez\u201d, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58060, Michoac\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nallely","family":"Garcia-Larragoiti","sequence":"additional","affiliation":[{"name":"Laboratorio de Hemostasia y Biolog\u00eda Vascular, Divisi\u00f3n de Estudios de Posgrado, Facultad de Ciencias M\u00e9dicas y Biol\u00f3gicas \u201cDr. Ignacio Ch\u00e1vez\u201d, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58060, Michoac\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yesenia","family":"Ambriz-Murillo","sequence":"additional","affiliation":[{"name":"Laboratorio de Hemostasia y Biolog\u00eda Vascular, Divisi\u00f3n de Estudios de Posgrado, Facultad de Ciencias M\u00e9dicas y Biol\u00f3gicas \u201cDr. Ignacio Ch\u00e1vez\u201d, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58060, Michoac\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Velez-Chavez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Celular Humana, Divisi\u00f3n de Estudios de Posgrado, Facultad de Ciencias M\u00e9dicas y Biol\u00f3gicas \u201cDr. Ignacio Ch\u00e1vez\u201d, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58060, Michoac\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogelio","family":"Vega-Agavo","sequence":"additional","affiliation":[{"name":"Laboratorio de Hemostasia y Biolog\u00eda Vascular, Divisi\u00f3n de Estudios de Posgrado, Facultad de Ciencias M\u00e9dicas y Biol\u00f3gicas \u201cDr. Ignacio Ch\u00e1vez\u201d, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58060, Michoac\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4683-699X","authenticated-orcid":false,"given":"Gerardo","family":"Vazquez-Marrufo","sequence":"additional","affiliation":[{"name":"Centro Multidisciplinario de Estudios en Biotecnolog\u00eda-FMVZ, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Km 9.5 Carretera Morelia-Zinap\u00e9cuaro, Posta Veterinaria, Morelia 58893, Michoac\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6964-0581","authenticated-orcid":false,"given":"Ana Edith","family":"Higareda-Mendoza","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Celular Humana, Divisi\u00f3n de Estudios de Posgrado, Facultad de Ciencias M\u00e9dicas y Biol\u00f3gicas \u201cDr. Ignacio Ch\u00e1vez\u201d, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58060, Michoac\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3441-2989","authenticated-orcid":false,"given":"Alejandra","family":"Ochoa-Zarzosa","sequence":"additional","affiliation":[{"name":"Centro Multidisciplinario de Estudios en Biotecnolog\u00eda-FMVZ, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Km 9.5 Carretera Morelia-Zinap\u00e9cuaro, Posta Veterinaria, Morelia 58893, Michoac\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2801-643X","authenticated-orcid":false,"given":"Martha Eva","family":"Viveros-Sandoval","sequence":"additional","affiliation":[{"name":"Laboratorio de Hemostasia y Biolog\u00eda Vascular, Divisi\u00f3n de Estudios de Posgrado, Facultad de Ciencias M\u00e9dicas y Biol\u00f3gicas \u201cDr. Ignacio Ch\u00e1vez\u201d, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58060, Michoac\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1159\/000507423","article-title":"COVID-19 Outbreak: An Overview","volume":"64","author":"Ciotti","year":"2019","journal-title":"Chemotherapy"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.bj.2020.04.007","article-title":"COVID-19: The first documented coronavirus pandemic in history","volume":"43","author":"Liu","year":"2020","journal-title":"Biomed. 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