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Papers In Press, published online ahead of print May 23, 2003
Biomedical Engineering, Georgia Tech and Emory University, Atlanta, GA 30322
Corresponding Author: hanjoong.jo{at}bme.gatech.edu
Atherosclerosis 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, we identify bone morphogenic protein 4 (BMP4) as a mechanosensitive and pro-inflammatory gene product through DNA microarrays, protein expression, and functional studies. Exposing endothelial cells to OS increased BMP4 protein expression while LS decreased it. Also, 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 level of intercellular cell adhesion molecule-1 (ICAM-1) protein compared to those of non-diseased areas. Functionally, we show that OS and BMP4 induced ICAM-1 expression and monocyte adhesion by a NFkB-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.
J. Biol. Chem, 10.1074/jbc.M300703200
Submitted on January 21, 2003
Revised on May 22, 2003
Accepted on May 23, 2003
Bone morphogenic protein 4-produced in endothelial cells by oscillatory shear stress stimulates an inflammatory response
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