Details

Autor(en) / Beteiligte

• Sorescu, George P.
• Sykes, Michelle
• Weiss, Daiana
• Platt, Manu O.
• Saha, Aniket
• Hwang, Jinah
• Boyd, Nolan
• Boo, Yong C.
• Vega, J.David
• Taylor, W.Robert
• Jo, Hanjoong

Titel

Bone Morphogenic Protein 4 Produced in Endothelial Cells by Oscillatory Shear Stress Stimulates an Inflammatory Response

Ist Teil von

• The Journal of biological chemistry, 2003-08, Vol.278 (33), p.31128-31135

Ort / Verlag

Legacy CDMS: Elsevier Inc

Erscheinungsjahr

2003

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 NFκB-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.