The Effects Of AngⅡ On BMP-2 Expression In Human Umbilical Vein Endothelial Cells (HUVECs)

Background:Bone morphogenetic protein-2 (BMP-2) plays an important role in vascular development and vascular pathophysiological processes, Mice deficient in BMP-2 died of cardiac defects between days 7 and 10 of gestation before the formation of bone, suggesting the significant importance of BMP-2 in vascular development.BMP-2 is one of the known important anabolic factors not only affacting on bone formation and bone mineral content, but also on vascular calcification. Vascular calcification is commonly found in atherosclerosis, which is now recognized as a marker of atherosclerotic plaque burden. The vascular calcification is now known to be present in 80% of significant lesions of atherosclerosis .Cumulated evidences indicated that proteins controlling bone mineralization are also involved in the regulation of vascular calcification. Many key regulators of bone formation and bone structural proteins are expressed in atherosclerotic plaques.BMP-2 is a strong basic causative factor in vascular calcification, BMP-2 and BMP-4 have been most frequently associated with calcific arteriopathy, and its extent directly relates to the overall burden of atherosclerotic disease. Artery wall cells grown in culture are induced to become osteogenic by inflammatory and atherogenic stimuli. Furthermore, osteoblast-like cells and BMP-2 are found in calcified atherosclerotic plaques. Therefore, it is very important to investigate the function of BMP-2 in the vascular calcification. Many evidences also show that artery calcification is a common problem among the population with hypertension. RAS and AngⅡplays a key role in atherosclerosis process, however its roles in vascular calcification are unclear. This study will investigate the effects of AngⅡand AngⅡReceptor Antaonist Irbesartar on BMP-2 expression in human umbilical vein endothelial cells(HUVECs), which may provide a clue to the treatment way of prevention of vascular calcification.Objectives:To investigate the effects of AngⅡon BMP-2 expression in human umbilical vein cells. To explore the potential mechanism by which AngⅡaffects BMP-2.Methods:The cultured human umbilical vein cells were treated by AngⅡand Irbesartan separately or in combination; The levels of BMP-2 protein in the supernatant were measured by enzyme-linked immunosorbent assays (ELISA). Intra-cellular expression of NFkb-P65 was detected by Immunohistochemical method. Results:1 ) AngⅡcan enhance the supernatant BMP-2 levels in a dose-dependent fashion. The BMP-2 levels were increased from 14.76±1.44 2pg/ml in non-AngⅡgroup to 78.51±2.16pg/ml (p<0.05) in AngⅡ(20umol/L) stimulated group , Irbesartan decreased the AngⅡ-induced (20umol/L) BMP-2 from 78.51±2.16pg/ml to 22.62±2.47 pg/ml(p<0.05).2 ) Cellular immunohistochemical staining showed that AngⅡcould increase intra-cellular expression of NFkb-P65 in HUVECs, while Irbesartan can inhibit the upregulated NFkb-P65 induced by AngⅡ.Conclusion :1) AngⅡcould dose-dependently increase the expression of BMP-2 in HUVECs, while Irbesartan, an angiotension II receptor blocker (ARB), could partially supress AngⅡ-induced upregulation of BMP-2 .2) NF-KB pathyway may be the potential mechanism by which AngⅡinduce BMP-2 expression in HUVECs.