{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:53:41Z","timestamp":1792457621764,"version":"4.5.0"},"reference-count":67,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,4,11]]},"abstract":"<jats:p>Atherosclerotic plaque forms in regions of the vasculature exposed to disturbed flow. NF-\u03baB activation by fluid flow, leading to expression of target genes such as E-selectin, ICAM-1, and VCAM-1, may regulate early monocyte recruitment and fatty streak formation. Flow-induced NF-\u03baB activation is downstream of conformational activation of integrins, resulting in new integrin binding to the subendothelial extracellular matrix and signaling. Therefore, we examined the involvement of the extracellular matrix in this process. Whereas endothelial cells plated on fibronectin or fibrinogen activate NF-\u03baB in response to flow, cells on collagen or laminin do not. In vivo, fibronectin and fibrinogen are deposited at atherosclerosis-prone sites before other signs of atherosclerosis. Ligation of integrin \u03b12\u03b21 on collagen prevents flow-induced NF-\u03baB activation through a p38-dependent pathway that is activated locally at adhesion sites. Furthermore, altering the extracellular matrix to promote p38 activation in cells on fibronectin suppresses NF-\u03baB activation, suggesting a novel therapeutic strategy for treating atherosclerosis.<\/jats:p>","DOI":"10.1083\/jcb.200410073","type":"journal-article","created":{"date-parts":[[2005,4,5]],"date-time":"2005-04-05T00:30:35Z","timestamp":1112661035000},"page":"191-202","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":260,"title":["The subendothelial extracellular matrix modulates NF-\u03baB activation by flow"],"prefix":"10.1083","volume":"169","author":[{"given":"A. Wayne","family":"Orr","sequence":"first","affiliation":[{"name":"3Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Sanders","sequence":"additional","affiliation":[{"name":"3Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Bevard","sequence":"additional","affiliation":[{"name":"3Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Coleman","sequence":"additional","affiliation":[{"name":"3Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian J.","family":"Sarembock","sequence":"additional","affiliation":[{"name":"3Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908"},{"name":"4Internal Medicine, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin Alexander","family":"Schwartz","sequence":"additional","affiliation":[{"name":"1Department of Microbiology, University of Virginia, Charlottesville, VA 22908"},{"name":"2Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908"},{"name":"3Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908"},{"name":"5Mellon Prostate Cancer Research Center, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2005,4,4]]},"reference":[{"key":"2023072215451036200_BIB1","doi-asserted-by":"crossref","first-page":"22176","DOI":"10.1074\/jbc.274.32.22176","volume":"274","year":"1999","journal-title":"J. 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