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bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress stimulates an inflammatory responseAtherosclerosis is now viewed as an inflammatory disease occurring preferentially in arterial regions exposed to disturbed flow conditions, including oscillatory shear stress (OS), in branched arteries. In contrast, the arterial regions exposed to laminar shear (LS) are relatively lesion-free. The mechanisms underlying the opposite effects of OS and LS on the inflammatory and atherogenic processes are not clearly understood. Here, through DNA microarrays, protein expression, and functional studies, we identify bone morphogenic protein 4 (BMP4) as a mechanosensitive and pro-inflammatory gene product. Exposing endothelial cells to OS increased BMP4 protein expression, whereas LS decreased it. In addition, we found BMP4 expression only in the selective patches of endothelial cells overlying foam cell lesions in human coronary arteries. The same endothelial patches also expressed higher levels of intercellular cell adhesion molecule-1 (ICAM-1) protein compared with those of non-diseased areas. Functionally, we show that OS and BMP4 induced ICAM-1 expression and monocyte adhesion by a NFkappaB-dependent mechanism. We suggest that BMP4 is a mechanosensitive, inflammatory factor playing a critical role in early steps of atherogenesis in the lesion-prone areas.
Document ID
20040087677
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Sorescu, George P.
(Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University Atlanta, Georgia 30322, United States)
Sykes, Michelle
Weiss, Daiana
Platt, Manu O.
Saha, Aniket
Hwang, Jinah
Boyd, Nolan
Boo, Yong C.
Vega, J. David
Taylor, W. Robert
Jo, Hanjoong
Date Acquired
August 21, 2013
Publication Date
August 15, 2003
Publication Information
Publication: The Journal of biological chemistry
Volume: 278
Issue: 33
ISSN: 0021-9258
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: HL70531
CONTRACT_GRANT: HL67413
CONTRACT_GRANT: HL71014
Distribution Limits
Public
Copyright
Other
Keywords
NASA Program Fundamental Space Biology
NASA Discipline Cell Biology
Non-NASA Center