Serum osteoprotegerin in young survivors of myocardial infarction

Anders Vik; Ellen Brodin; Trond Børvik; Baldur Sveinbjørnsson; John-Bjarne Hansen

doi:10.1160/TH05-10-0662

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 95(05): 881-885
DOI: 10.1160/TH05-10-0662

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

Serum osteoprotegerin in young survivors of myocardial infarction

Authors

Anders Vik

¹Center for Atherothrombotic Research in Tromsø (CART), Department of Medicine, Institute of Clinical Medicine and Department of Experimental Pathology, Institute of Medical Biology, University of Tromsø, Tromsø, Norway
Ellen Brodin

¹Center for Atherothrombotic Research in Tromsø (CART), Department of Medicine, Institute of Clinical Medicine and Department of Experimental Pathology, Institute of Medical Biology, University of Tromsø, Tromsø, Norway
Trond Børvik

¹Center for Atherothrombotic Research in Tromsø (CART), Department of Medicine, Institute of Clinical Medicine and Department of Experimental Pathology, Institute of Medical Biology, University of Tromsø, Tromsø, Norway
Baldur Sveinbjørnsson

¹Center for Atherothrombotic Research in Tromsø (CART), Department of Medicine, Institute of Clinical Medicine and Department of Experimental Pathology, Institute of Medical Biology, University of Tromsø, Tromsø, Norway

^*Department of Medicine, Institute of Clinical Medicine and Department of Experimental Pathology
John-Bjarne Hansen

¹Center for Atherothrombotic Research in Tromsø (CART), Department of Medicine, Institute of Clinical Medicine and Department of Experimental Pathology, Institute of Medical Biology, University of Tromsø, Tromsø, Norway

Abstract

Summary

Osteoprotegerin (OPG) is a member of the tumour necrosis factor superfamily and is involved in the regulation of bone metabolism and vascular calcification. Increased serum OPG levels have been reported in patients with stable angina pectoris and survivors of myocardial infarction with heart failure. The purpose of the present study was to determine serum OPG levels in young survivors of acute myocardial infarction (MI), and the relationship between OPG, homocysteine, sCD40L and coagulation factors in blood. Fifty-eight patients with verified MI, 40–60 years of age, were recruited 1–4 years after the acute event into an age- and sex- matched case control study with controls recruited from the general population. Serum OPG levels were similar in cases (2.41 ng/ml, 2.11–2.77 ng/ml) (mean, 95% CI) and controls (2.43 ng/ml, 2.11–2.79 ng/ml) (p= 0.92). Significant correlation between OPG and homocysteine was found in patients (r=0.30, p=0.02) and controls (r=0.35, p=0.007). A significant negative correlation was found between OPG and sCD40L in patients (r=-0.51, p<0.001), but not in controls (r=0.001, p=0.96). No associations were found between serum OPG and markers of coagulation activation. The present study shows that serum OPG level was not increased in young survivors of uncomplicated myocardial infarction. Serum OPG levels were not associated with thrombin generation assessed by thrombin-antithrombin complexes (TAT), but a positive association between serum OPG and homocysteine was found.

Keywords

Osteoprotegerin - homocysteine - coagulation - thrombin generation - myocardial infarction

Full Text

References

References
1 Browner WS. et al. Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women. J Clin Endocrinol Metab 2001; 86: 631-7.
2 Hofbauer LC, Schoppet M. Osteoprotegerin:a link between osteoporosis and arterial calcification?. Lancet 2001; 358: 257-9.
3 Simonet WS. et al. Osteoprotegerin: A novel secreted protein involved in the regulation of bone density. Cell 1997; 89: 309-19.
4 Tan KB. et al. Characterization of a novel TNF-like ligand and recently described TNF ligand and TNF receptor superfamily genes and their constitutive and inducible expression in hematopoietic and non-hematopoietic cells. Gene 1997; 204: 35-46.
5 Yun TJ. et al. OPG/FDCR-1, a TNF receptor family member, is expressed in lymphoid cells and is up-regulated by ligating CD40. J Immunol 1998; 161: 6113-21.
6 Dhore CR. et al. Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques. Arterioscler Thromb Vasc Biol 2001; 21: 1998-2003.
7 Zhang J. et al. PDGF induces osteoprotegerin expression in vascular smooth muscle cells by multiple signal pathways. FEBS Lett 2002; 521: 180-4.
8 Malyankar UM. et al. Osteoprotegerin Is an αvβ3-induced, NF-κB-dependent survival factor for endothelial cells. J Biol Chem 2000; 275: 20959-62.
9 Pritzker LB. et al. The role of osteoprotegerin and tumor necrosis factor-related apoptosis-inducing ligand in human microvascular endothelial cell survival. Mol Biol Cell 2004; 15: 2834-41.
10 Chagraoui H. et al. Expression of osteoprotegerin mRNA and protein in murine megakaryocytes. Exp Hematol 2003; 31: 1081-8.
11 Yasuda H. et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. PNAS 1998; 95: 3597-602.
12 Emery JG. et al. Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem 1998; 273: 14363-7.
13 Wong BR. et al. TRANCE (Tumor Necrosis Factor [TNF]-related Activation-induced Cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor. J Exp Med 1997; 186: 2075-80.
14 Anderson DM. et al. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature 1997; 390: 175-9.
15 Golledge J. et al. Osteoprotegerin and osteopontin are expressed at high concentrations within symptomatic carotid atherosclerosis. Stroke 2004; 35: 1636-41.
16 Zannettino AC. et al. Osteoprotegerin (OPG) is localized to the Weibel-Palade bodies of human vascular endothelial cells and is physically associated with von Willebrand factor. J Cell Physiol 2005; 204: 714-23.
17 Jono S. et al. Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease. Circulation 2002; 106: 1192-4.
18 Schoppet M. et al. Increased osteoprotegerin serum levels in men with coronary artery disease. J Clin Endocrinol Metab 2003; 88: 1024-8.
19 Kiechl S. et al. Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease. Circulation 2004; 109: 2175-80.
20 Ueland T. et al. Prognostic value of osteoprotegerin in heart failure after acute myocardial infarction. J Am Coll Cardiol 2004; 44: 1970-6.
21 Ross R. Atherosclerosis -- An inflammatory disease. N Engl J Med 1999; 340: 115-26.
22 Burstein M. et al. Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions. J Lipid Res 1970; 11: 583-95.
23 Friedewald W. et al. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502.
24 Sandset PM. et al. Chromogenic substrate assay of extrinsic pathway inhibitor (EPI): levels in the normal population and relation to cholesterol. Blood Coagul Fibrinolysis 1991; 2: 425-33.
25 Øtergaard PB. et al. An enzyme linked immunosorption assay for tissue factor pathway inhibitor. Thrombosis Research 1997; 87: 447-59.
26 Morrissey JH. et al. Quantitation of activated factor VII levels in plasma using a tissue factor mutant selectively deficient in promoting factor VII activation. Blood 1993; 81: 734-44.
27 Bucay N. et al. Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 1998; 12: 1260-8.
28 Kaden JJ. et al. Receptor activator of nuclear factor kappa B ligand and osteoprotegerin regulate aortic valve calcification. J Mol Cell Cardiol 2004; 36: 57-66.
29 Price PA. et al. Osteoprotegerin inhibits artery calcification induced by warfarin and by vitamin D. Arterioscler Thromb Vasc Biol 2001; 21: 1610-6.
30 Tyson KL. et al. Osteo/chondrocytic transcription factors and their target genes exhibit distinct patterns of expression in human arterial calcification. Arterioscler Thromb Vasc Biol 2003; 23: 489-94.
31 Sandberg WJ. et al. Enhanced T-cell expression of RANK ligand in acute coronary syndrome. Possible role in plaque destabilization. Arterioscler Thromb Vasc Biol. 2006 DOI: 01.ATV.0000204334.48195.6a.
32 Crisafulli A. et al. Serum levels of osteoprotegerin and RANKL in patients with ST elevation acute myocardial infarction. Clin Sci (Lond) 2005; 109: 389-95.
33 Ueland T. et al. Dysregulated osteoprotegerin/ RANK ligand/RANK axis in clinical and experimental heart failure. Circulation 2005; 111: 2461-8.
34 Perutelli P. et al. von Willebrand factor multimer composition is modified following oral methionine load in women with thrombosis, but not in healthy women. Blood Coagul Fibrinolysis 2005; 16: 267-73.
35 Nygard O. et al. Total homocysteine and cardiovascular disease. J Int Med 1999; 246: 425-54.
36 Libby P. Current concepts of the pathogenesis of the acute coronary syndromes. Circulation 2001; 104: 365-72.
37 Henn V. et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 1998; 391: 591-4.
38 Heeschen C. et al. Soluble CD40 ligand in acute coronary syndromes. N Engl J Med 2003; 348: 1104-11.
39 Varo N. et al. Soluble CD40L: Risk prediction after acute coronary syndromes. Circulation 2003; 108: 1049-52.