¹Department of Genetics, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan

Correspondence: Professor M Shibuya, Department of Genetics, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan. E-mail: shibuya@ims.u-tokyo.ac.jp

Received 23 December 2005; Revised 10 April 2006; Accepted 18 April 2006; Published online 29 May 2006.

Abstract

Arterial endothelial cells (EC) at the adult stage differ from capillary and venous EC in terms of resistance to stress; however, the molecular basis of this resistance is not clear. Here, we found that arterial EC are highly resistant to bone morphogenetic protein (BMP)4-dependent apoptosis, whereas capillary and venous EC are not. The expression of inhibitory Smads (I-Smads) in arterial EC was well correlated with the resistance to this apoptosis. After the knockdown of I-Smad expression by short interfering RNA, the resistant arterial EC became sensitive to BMP4. In contrast, the ectopic expression of I-Smads in BMP4-sensitive cells suppressed BMP4-induced apoptosis. Furthermore, intravenous administration of BMP4 into mice caused hemorrhage of capillary EC in brain and lung. These results strongly suggest that BMP4/I-Smads are a novel regulator for the stability of vascular EC.