Journal
JOURNAL OF CELL BIOLOGY
Volume 169, Issue 1, Pages 191-202Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200410073
Keywords
-
Categories
Funding
- NHLBI NIH HHS [R01 HL066264, R01 HL075092, 1R01HL66264, R01 HL75092] Funding Source: Medline
Ask authors/readers for more resources
Atherosclerotic plaque forms in regions of the vasculature exposed to disturbed flow. NF-B-K 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-B-K 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-B-K 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 alpha 2 beta 1 on collagen prevents flow-induced NF-B-K 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-B-K activation, suggesting a novel therapeutic strategy for treating atherosclerosis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available