Regulation of Bone Morphogenetic Protein-2 Expression in Endothelial Cells

Abstract

Background— Recent studies suggest that bone morphogenetic protein-2 (BMP-2), a transforming growth factor-β superfamily member cytokine, plays an important role both in vascular development and pathophysiological processes, including endothelial activation that is likely to contribute to the development of coronary atherosclerosis, yet the factors that regulate arterial expression of BMP-2 are completely unknown. We tested the hypothesis that BMP-2 expression in endothelial cells is governed by an H2O2 and nuclear factor (NF)-κΒ–dependent pathway that can be activated by both proinflammatory and mechanical stimuli. Methods and Results— The proinflammatory cytokine tumor necrosis factor (TNF)-α induced NF-κΒ activation and elicited significant increases in BMP-2 mRNA and protein in primary coronary arterial endothelial cells and human umbilical vein endothelial cells that were prevented by NF-κΒ inhibitors (pyrrolidine dithiocarbamate and SN-50), silencing of p65 (siRNA), or catalase. Administration of H2...