Endothelial Cell Activation by SARS-CoV-2 Spike Protein and Its RBD: Central Player of the Immunothrobotic Response in COVID-19

DOI record: { "DOI": "10.3390/cimb48020161", "ISSN": [ "1467-3045" ], "URL": "http://dx.doi.org/10.3390/cimb48020161", "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>", "alternative-id": [ "cimb48020161" ], "author": [ { "ORCID": "https://orcid.org/0009-0009-8620-0962", "affiliation": [ { "name": "Laboratorio de Hemostasia y Biología Vascular, División de Estudios de Posgrado, Facultad de Ciencias Médicas y Biológicas “Dr. Ignacio Chávez”, Universidad Michoacana de San Nicolás de Hidalgo, Morelia 58060, Michoacán, Mexico" } ], "authenticated-orcid": false, "family": "Cano-Mendez", "given": "Alan", "sequence": "first" }, { "affiliation": [ { "name": "Laboratorio de Hemostasia y Biología Vascular, División de Estudios de Posgrado, Facultad de Ciencias Médicas y Biológicas “Dr. Ignacio Chávez”, Universidad Michoacana de San Nicolás de Hidalgo, Morelia 58060, Michoacán, Mexico" } ], "family": "Garcia-Larragoiti", "given": "Nallely", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratorio de Hemostasia y Biología Vascular, División de Estudios de Posgrado, Facultad de Ciencias Médicas y Biológicas “Dr. Ignacio Chávez”, Universidad Michoacana de San Nicolás de Hidalgo, Morelia 58060, Michoacán, Mexico" } ], "family": "Ambriz-Murillo", "given": "Yesenia", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratorio de Biología Celular Humana, División de Estudios de Posgrado, Facultad de Ciencias Médicas y Biológicas “Dr. Ignacio Chávez”, Universidad Michoacana de San Nicolás de Hidalgo, Morelia 58060, Michoacán, Mexico" } ], "family": "Velez-Chavez", "given": "Jennifer", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratorio de Hemostasia y Biología Vascular, División de Estudios de Posgrado, Facultad de Ciencias Médicas y Biológicas “Dr. Ignacio Chávez”, Universidad Michoacana de San Nicolás de Hidalgo, Morelia 58060, Michoacán, Mexico" } ], "family": "Vega-Agavo", "given": "Rogelio", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-4683-699X", "affiliation": [ { "name": "Centro Multidisciplinario de Estudios en Biotecnología-FMVZ, Universidad Michoacana de San Nicolás de Hidalgo, Km 9.5 Carretera Morelia-Zinapécuaro, Posta Veterinaria, Morelia 58893, Michoacán, Mexico" } ], "authenticated-orcid": false, "family": "Vazquez-Marrufo", "given": "Gerardo", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0001-6964-0581", "affiliation": [ { "name": "Laboratorio de Biología Celular Humana, División de Estudios de Posgrado, Facultad de Ciencias Médicas y Biológicas “Dr. Ignacio Chávez”, Universidad Michoacana de San Nicolás de Hidalgo, Morelia 58060, Michoacán, Mexico" } ], "authenticated-orcid": false, "family": "Higareda-Mendoza", "given": "Ana Edith", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-3441-2989", "affiliation": [ { "name": "Centro Multidisciplinario de Estudios en Biotecnología-FMVZ, Universidad Michoacana de San Nicolás de Hidalgo, Km 9.5 Carretera Morelia-Zinapécuaro, Posta Veterinaria, Morelia 58893, Michoacán, Mexico" } ], "authenticated-orcid": false, "family": "Ochoa-Zarzosa", "given": "Alejandra", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-2801-643X", "affiliation": [ { "name": "Laboratorio de Hemostasia y Biología Vascular, División de Estudios de Posgrado, Facultad de Ciencias Médicas y Biológicas “Dr. Ignacio Chávez”, Universidad Michoacana de San Nicolás de Hidalgo, Morelia 58060, Michoacán, Mexico" } ], "authenticated-orcid": false, "family": "Viveros-Sandoval", "given": "Martha Eva", "sequence": "additional" } ], "container-title": "Current Issues in Molecular Biology", "container-title-short": "CIMB", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2026, 2, 2 ] ], "date-time": "2026-02-02T09:48:08Z", "timestamp": 1770025688000 }, "deposited": { "date-parts": [ [ 2026, 2, 2 ] ], "date-time": "2026-02-02T10:23:21Z", "timestamp": 1770027801000 }, "funder": [ { "award": [ "320085" ], "award-info": [ { "award-number": [ 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