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Moreover, multiorgan complications due to persistent endothelial dysfunction have been suspected as the cause of post-acute sequelae of SARS-CoV-2 infection. Therefore, elucidation of the vascular inflammatory effect of SARS-CoV-2 will increase our understanding of how endothelial cells (ECs) contribute to the short- and long-term consequences of SARS-CoV-2 infection. Here, we investigated the interaction of SARS-CoV-2 spike protein with human ECs from aortic (HAoEC) and pulmonary microvascular (HPMC) origins, cultured under physiological flow conditions. We showed that the SARS-CoV-2 spike protein triggers prolonged expression of cell adhesion markers in both ECs, similar to the effect of TNF-\u03b1. SARS-CoV-2 spike treatment also led to the release of various cytokines and chemokines observed in severe COVID-19 patients. Moreover, increased binding of leucocytes to the endothelial surface and a procoagulant state of the endothelium were observed. Transcriptomic profiles of SARS-CoV-2 spike-activated HPMC and HAoEC showed prolonged upregulation of genes and pathways associated with responses to virus, cytokine-mediated signaling, pattern recognition, as well as complement and coagulation pathways. Our findings support experimental and clinical observations of the vascular consequences of SARS-CoV-2 infection and highlight the importance of EC protection as one of the strategies to mitigate the severe effects as well as the possible post-acute complications of COVID-19 disease.<\/jats:p>","DOI":"10.1007\/s10753-024-02208-x","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T19:20:23Z","timestamp":1735586423000},"page":"2531-2547","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Sustained Vascular Inflammatory Effects of SARS-CoV-2 Spike Protein on Human Endothelial Cells"],"prefix":"10.1007","volume":"48","author":[{"given":"Mitra","family":"Gultom","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla Blunk","family":"Brandt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Milusev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Despont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"D\u00f6ring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonglun","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Rieben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,31]]},"reference":[{"issue":"7","key":"2208_CR1","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/s41577-020-0343-0","volume":"20","author":"L-A Teuwen","year":"2020","unstructured":"Teuwen, L.-A., V. Geldhof, A. Pasut, and P. Carmeliet. 2020. COVID-19: The vasculature unleashed. Nature Reviews Immunology 20 (7): 389\u2013391. https:\/\/doi.org\/10.1038\/s41577-020-0343-0.","journal-title":"Nature Reviews Immunology"},{"issue":"9","key":"2208_CR2","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1161\/ATVBAHA.120.314513","volume":"40","author":"BS Kadosh","year":"2020","unstructured":"Kadosh, B.S., et al. 2020. COVID-19 and the Heart and Vasculature: Novel Approaches to Reduce Virus-Induced Inflammation in Patients With Cardiovascular Disease. Arteriosclerosis, Thrombosis, and Vascular Biology 40 (9): 2045\u20132053. https:\/\/doi.org\/10.1161\/ATVBAHA.120.314513.","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"issue":"8","key":"2208_CR3","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1161\/CIRCRESAHA.121.317997","volume":"128","author":"MK Chung","year":"2021","unstructured":"Chung, M.K., et al. 2021. COVID-19 and Cardiovascular Disease: From Bench to Bedside. Circulation Research 128 (8): 1214\u20131236. https:\/\/doi.org\/10.1161\/CIRCRESAHA.121.317997.","journal-title":"Circulation Research"},{"issue":"2","key":"2208_CR4","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1056\/NEJMoa2015432","volume":"383","author":"M Ackermann","year":"2020","unstructured":"Ackermann, M., et al. 2020. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. New England Journal of Medicine 383 (2): 120\u2013128. https:\/\/doi.org\/10.1056\/NEJMoa2015432.","journal-title":"New England Journal of Medicine"},{"issue":"10247","key":"2208_CR5","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/S0140-6736(20)31305-2","volume":"396","author":"BT Bradley","year":"2020","unstructured":"Bradley, B.T., et al. 2020. Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: A case series. 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