,Involvment of BMP Signaling in Proliferation of Human Coronary Artery Endothelial Cells

• 作 者: Suzhen Guo Terence M Doherty Jun Xu Andres J.Espinoza
• 机 构: The Atherosclerosis Research Center,Division of Cardiology,Department of Medicine and The Burns and
• 出 处: 岭南心血管病杂志（英文版）
• 发表日期: 2008年2期
• 关键词: bone morphogenetic proteins bone morphogenetic protein receptors endothelial cel

Objectives To test the hypotheses that bone morphogenedc protein (BMP) signaling pathway components axe expressed in arterial endothelial cells (ECs) and that BMP signaling influences endothelial cell(EC) proliferation.Methods We used cell culture and RT-PCR to determined mRNA expression of BMP receptors (BMPR)-IA,-IB,and Ⅱ,Smads 1,4,5,6,and 7,and in cultured human coronary artery ECs at baseline and after stimulation with BMP2 (300 ng/mL for 6 hr),non-radioactive cell proliferation to examine cell proliferation.Results Proteasome inhibition has been previously shown to enhance BMP signaling by preventing degradation of BMP pathway components.Therefore,identical experiments were also performed in the presence of the proteasome inhibitor epoxomicin.ECs expressed mRNA for BMPRs IA and II,Smads 1,4,5,6,7,and stimulation with either BMP2 or epoxomicin resulted in a significant increase in EC proliferation measured after 48 hours in a dose-dependent fashion.Proliferation was accompanied by a marked increase in proliferating cell nuclear antigen (PCNA) expression.Toxicity was observed at high doses of epoxomicin.Conclusions All major BMP signaling molecules are expressed by vascular ECs and expression of these are affected by both BMP2 and epoxomicin.BMP2 may regulate EC proliferation,suggesting a possible role in vascular homeostasis and vascular pathologies involving EC denudation or proliferation.