Bone morphogenetic protein-2 (BMP-2), a transforming growth factor-β superfamily member cytokine, plays a key role both in vascular development and in pathophysiological processes. However, the effects and mechanisms of angiotensin II (Ang II) on BMP-2 expression remain unknown in human umbilical vein endothelial cells (HUVECs). Here we show that Ang II treatment significantly increased BMP-2 expression, associated with NF-κB activation, which was suppressed by treatment with pyrrolidine dithiocarbamate (PDTC) or irbesartan. Furthermore, the increased levels of MDA (malondialdehyde) in conditioned media and the decrease in activities of total superoxide dismutases (SOD) caused by Ang II were reversed by irbesartan or PDTC treatment. Our findings indicate that Ang II-induced BMP-2 expression might contribute to NF-κB activation. BMP-2 expression induced by Ang II might involve excessive oxidative stress.
1 Abedin M Tintut Y Demer LL . Vascular calcification: mechanisms and clinical ramifications. Arterioscler Thromb Vasc Biol2004; 24: 1161–1170.
2.
2 Csiszar A Smith KE Koller A . Regulation of bone morphogenetic protein-2 expression in endothelial cells: role of nuclear factor-kappaB activation by tumor necrosis factor-alpha, H2O2, and high intravascular pressure. Circulation2005; 111: 2364–2372.
3.
3 Johnson RC Leopold JA Loscalzo J . Vascular calcification: pathobiological mechanisms and clinical implications. Circ Res2006; 99: 1044–1059.
4.
4 Shanahan CM Cary NR Metcalfe JC . High expression of genes for calcification-regulating proteins in human atherosclerotic plaques. J Clin Invest1994; 93: 2393–2402.
5.
5 Demer L Watson KE Bostrom K . Mechanism of calcification in atherosclerosis. Circulation2005; 111: 2364–2372.
6.
6 Hruska KA Mathew S Saab G . Bone morphogenetic proteins in vascular calcification. Circ Res2005; 97: 105–114.
7.
7 Parhami F Bostrom K Watson K . Role of molecular regulation in vascular calcification. J Atheroscler Thromb1996; 3: 90–94.
8.
8 Libby P Ridker PM Maseri A . Inflammation and atherosclerosis. Circulation2002; 105: 1135–1143.
9.
9 Kranzhofer R Schmidt J Pfeiffer CA . Angiotensin induces inflammatory activation of human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol1999; 19: 1623–1629.
10.
10 Tummala PE Chen XL Sundell CL . Angiotensin II induces vascular cell adhesion molecule-1 expression in rat vasculature: a potential link between the renin-angiotensin system and atherosclerosis. Circulation1999; 100: 1223–1229.
11.
11 Morawietz H Erbs S Holtz J . Endothelial protection, AT1 blockade and cholesterol-dependent oxidative stress: the EPAS trial. Circulation2006; 114 (Suppl 1): I296–I330.
12.
12 Hernandez-Presa M Bustos C Ortego M . Angiotensin-converting enzyme inhibition prevents arterial nuclear factor-κB activation, monocyte chemoattractant protein-1 expression, and macrophage infiltration in a rabbit model of early accelerated atherosclerosis. Circulation1997; 95: 1532–1541.
13.
13 Zhang WJ Wojta J Binder BR . Notoginsenoside R1 counteracts endotoxin-induced activation of endothelial cells in vitro and endotoxin-induced lethality in mice in vivo. Arterioscler Thromb Vasc Biol1997; 17: 465–474.
14.
14 Kapoor R Prasad K . Role of oxyradicals in cardiovascular depression and cellular injury in hemorrhagic shock and reinfusion: effect of SOD and catalase. Circ Shock1994; 43: 79–94.
15.
15 Ohkawa H Ohishi N Yagi K . Assay for lipid peroxides in animal tissue by thiobarbituric acid reaction. Anal Biochem1979; 95: 351–358.
16.
16 Fukai T Galis Z Meng XP . Vascular expression of extracellular superoxide dismutase in atherosclerosis. J Clin Invest1998; 101: 2101–2111.
17.
17 Assem M Teyssier J-R Benderitter M . Pattern of superoxide dismutase enzymatic activity and RNA changes in rat heart ventricles after myocardial infarction. Am J Pathol1997; 151: 549–555.
18.
18 Lowry O Rosebrough N Farr A . Protein measurement with the folin-phenol reagent. J Biol Chem1951; 193: 265–275.
19.
19 Oyama VI Eagle H . Measurement of cell growth in tissue culture with a phenol reagent (Folin-Ciocalteau). Proc Soc Exp Biol Med1956; 91: 305–307.
20.
20 Zhang H Bradley A . Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development1996; 122: 2977–2986.
21.
21 Suzuki Y Ruiz-Ortega M Lorenzo O . Inflammation and angiotensin II. Int J Biochem Cell Biol2003; 35: 881–900.
22.
22 Ferrario CM Strawn WB . Role of the renin-angiotensin-aldosterone system and proinflammatory mediators in cardiovascular disease. Am J Cardiol2006; 98: 121–128.
23.
23 Hernan dez-Presa, M, Bustos, C, Ortego, M, et al. Angiotensin-converting enzyme inhibition prevents arterial nuclear factor-κB activation, monocyte chemoattractant protein-1 expression, and macrophage infiltration in a rabbit model of early accelerated atherosclerosis. Circulation 1997; 95: 1532–1541.
24.
24 Tsikouris JP Cox CD . Pharmacologic blockade of the renin-angiotensin system: vascular benefits beyond commonly understood pharmacologic actions. Pharmacotherapy2003; 23: 1141–1152.
25.
25 Pueyo ME Gonzalez W Nicoletti A Savoie F Arnal JF Michel JB . Angiotensin II stimulates endothelial vascular cell adhesion molecule-1 via nuclear factor-κB activation induced by intracellular oxidative stress. Arterioscler Thromb Vasc Biol2000; 20: 645–651.
26.
26 Nowicki PT Flavahan S Hassanain H . Redox signaling of the arteriolar myogenic response. Circ Res2001; 89: 114–116.
27.
27 Sawayama Y Shimizu C Maeda N . Effects of probucol and pravastatin on common carotid atherosclerosis in patients with asymptomatic hypercholesterolemia: Fukuoka Atherosclerosis Trial (FAST). J Am Coll Cardiol2002; 39: 610–616.
28.
28 Mackness B Durrington PN Mackness MI . Lack of protection against oxidative modification of LDL by avian HDL. Biochem Biophys Res Commun1998; 247: 443–446.
29.
29 Traverso N Menini S Maineri EP . Malondialdehyde, a lipoperoxidation-derived aldehyde, can bring about secondary oxidative damage to proteins. J Gerontol A Biol Sci Med Sci2004; 59: B890–B895.
