Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress stimulates an inflammatory response.
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, 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.
Sorescu
George P
GP
Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Atlanta, Georgia 30322, USA.
Sykes
Michelle
M
Weiss
Daiana
D
Platt
Manu O
MO
Saha
Aniket
A
Hwang
Jinah
J
Boyd
Nolan
N
Boo
Yong C
YC
Vega
J David
JD
Taylor
W Robert
WR
Jo
Hanjoong
H
D000818:Animals; D001011:Aorta / Q000166:cytology; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005487:Foam Cells / Q000276:immunology / Q000473:pathology; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D051379:Mice; D009000:Monocytes / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D013314:Stress, Mechanical; D014657:Vasculitis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
C525809:BMP4 protein, human; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1