Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease

被引:476
作者
Jono, S
Ikari, Y
Shioi, A
Mori, K
Miki, T
Hara, K
Nishizawa, Y
机构
[1] Osaka City Univ, Grad Sch Med, Dept Metab Endocrinol & Mol Med, Abeno Ku, Osaka 5458585, Japan
[2] Osaka City Univ, Grad Sch Med, Dept Cardiovasc Med, Osaka 558, Japan
[3] Osaka City Univ, Grad Sch Med, Dept Geriatr & Neurol, Osaka 558, Japan
[4] Mitsui Mem Hosp, Div Cardiol, Tokyo 101, Japan
关键词
glycoproteins; coronary disease; atherosclerosis;
D O I
10.1161/01.CIR.0000031524.49139.29
中图分类号
R5 [内科学];
学科分类号
1002 [临床医学]; 100201 [内科学];
摘要
Background-Osteoprotegerin (OPG) is a secretory glycoprotein that belongs to the tumor necrosis factor receptor family. OPG-deficient mice develop severe osteoporosis and medial arterial calcification of the aorta and renal arteries. OPG immunoreactivity was demonstrated in the normal blood vessels and in early atherosclerotic lesions. A recent clinical study suggests that there is a significant correlation between elevated serum OPG levels and cardiovascular mortality. We examined whether serum OPG levels are associated with the progression of coronary artery disease (CAD). Methods and Results-Serum OPG levels were examined in 201 patients who underwent coronary angiography because of stable chest pain. The number of diseased vessels was used to represent the severity of CAD. Serum OPG levels were measured by ELISA and were significantly greater in patients with significant stenosis of the coronary arteries than in those without stenosis. As the severity of CAD increased, there was a significant increase in serum OPG levels. Serum OPG levels were 0.94 +/- 0,34, 1.04 +/- 0.38, 1.19 +/- 0.38, and 1.44 +/- 0.54 ng/mL (medians 0.91, 0.99, 1.09, and 1.37) for the subjects with normal coronary arteries or luminal irregularities, 1-vessel disease, 2-vessel disease, and 3-vessel disease, respectively. Multivariate logistic regression analysis revealed that serum OPG levels were significantly associated with the presence of CAD [odds ratio, 5.2; 95% confidence interval, 1.7 to 16.0]. Conclusions-Our data show that serum OPG levels are associated with the presence and severity of CAD, suggesting that OPG may be involved in the progression of CAD.
引用
收藏
页码:1192 / 1194
页数:3
相关论文
共 13 条
[1]
Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women [J].
Browner, WS ;
Lui, LY ;
Cummings, SR .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (02) :631-637
[2]
osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification [J].
Bucay, N ;
Sarosi, I ;
Dunstan, CR ;
Morony, S ;
Tarpley, J ;
Capparelli, C ;
Scully, S ;
Tan, HL ;
Xu, WL ;
Lacey, DL ;
Boyle, WJ ;
Simonet, WS .
GENES & DEVELOPMENT, 1998, 12 (09) :1260-1268
[3]
Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques [J].
Dhore, CR ;
Cleutjens, JPM ;
Lutgens, E ;
Cleutjens, KBJM ;
Geusens, PPM ;
Kitslaar, PJEHM ;
Tordoir, JHM ;
Spronk, HMH ;
Vermeer, C ;
Daemen, MJAP .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2001, 21 (12) :1998-2003
[4]
Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL [J].
Emery, JG ;
McDonnell, P ;
Burke, MB ;
Deen, KC ;
Lyn, S ;
Silverman, C ;
Dul, E ;
Appelbaum, ER ;
Eichman, C ;
DiPrinzio, R ;
Dodds, RA ;
James, IE ;
Rosenberg, M ;
Lee, JC ;
Young, PR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (23) :14363-14367
[5]
The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption [J].
Hofbauer, LC ;
Khosla, S ;
Dunstan, CR ;
Lacey, DL ;
Boyle, WJ ;
Riggs, BL .
JOURNAL OF BONE AND MINERAL RESEARCH, 2000, 15 (01) :2-12
[6]
Effects of immunosuppressants on receptor activator of NF-κB ligand and osteoprotegerin production by human osteoblastic and coronary artery smooth muscle cells [J].
Hofbauer, LC ;
Shui, CX ;
Riggs, BL ;
Dunstan, CR ;
Spelsberg, TC ;
O'Brien, T ;
Khosla, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 280 (01) :334-339
[7]
OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis [J].
Kong, YY ;
Yoshida, H ;
Sarosi, I ;
Tan, HL ;
Timms, E ;
Capparelli, C ;
Morony, S ;
Oliveira-dos-Santos, AJ ;
Van, G ;
Itie, A ;
Khoo, W ;
Wakeham, A ;
Dunstan, CR ;
Lacey, DL ;
Mak, TW ;
Boyle, WJ ;
Penninger, JM .
NATURE, 1999, 397 (6717) :315-323
[8]
Osteoprotegerin is an αvβ3-induced, NF-κB-dependent survival factor for endothelial cells [J].
Malyankar, UM ;
Scatena, M ;
Suchland, KL ;
Yun, TJ ;
Clark, EA ;
Giachelli, CM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (28) :20959-20962
[9]
Osteoprotegerin reverses osteoporosis by inhibiting endosteal osteoclasts and prevents vascular calcification by blocking a process resembling osteoclastogenesis [J].
Min, H ;
Morony, S ;
Sarosi, I ;
Dunstan, CR ;
Capparelli, C ;
Scully, S ;
Van, G ;
Kaufman, S ;
Kostenuik, PJ ;
Lacey, DL ;
Boyle, TJ ;
Simonet, WS .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (04) :463-474
[10]
Mechanisms of disease - Atherosclerosis - An inflammatory disease [J].
Ross, R .
NEW ENGLAND JOURNAL OF MEDICINE, 1999, 340 (02) :115-126