Change of Plasma Osteoprotegerin and its Association with Endothelial Dysfunction before and after Exercise in Hashimoto’s Thyroiditis with Euthyroidism

G. Xiang; L. Xiang; L. Xiang; H. Wang; J. Dong

doi:10.1055/s-0032-1323806

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2012; 120(09): 529-534
DOI: 10.1055/s-0032-1323806

Article

Change of Plasma Osteoprotegerin and its Association with Endothelial Dysfunction before and after Exercise in Hashimoto’s Thyroiditis with Euthyroidism

G. Xiang

¹Department of Endocrinology, Wuhan General Hospital of Guangzhou Command, Wuhan, Hubei Province, P. R. China

,

L. Xiang

¹Department of Endocrinology, Wuhan General Hospital of Guangzhou Command, Wuhan, Hubei Province, P. R. China

,

L. Xiang

²College of Life Science, Hubei University, Wuhan, Hubei Province, P. R. China

,

H. Wang

¹Department of Endocrinology, Wuhan General Hospital of Guangzhou Command, Wuhan, Hubei Province, P. R. China

,

J. Dong

¹Department of Endocrinology, Wuhan General Hospital of Guangzhou Command, Wuhan, Hubei Province, P. R. China

› Author Affiliations

Abstract

Objective:

Osteoprotegerin (OPG) is a recently identified inhibitor of bone resorption. Recent studies indicated that OPG also acts as an important regulatory molecule in the vasculature. The purpose of this study was to investigate the change of OPG and its associations with endothelial function before and after exercise training in Hashimoto’s thyroiditis (HT) with euthyroidism.

Materials/Methods:

The study subjects included 62 newly diagnosed sedentary Chinese Han HT women with euthyroidism and 28 sedentary Chinese Han female healthy subjects. All individuals participated in an exercise training of 6 months. Plasma OPG concentrations were measured in duplicate by a sandwich enzyme-linked immunosorbent assay, and high resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia, and after sublingual glyceryltrinitrate.

Results:

The OPG concentration in HT patients with euthyroidism before exercise was 3.0±0.81 ng/L, which was significantly higher than that in control subjects (2.44±0.24 ng/L, p<0.001). After 6 months of exercise, OPG levels decreased markedly (2.40±0.61 ng/L, p<0.001). Flow-mediated dilation (FMD) in HT patients with euthyroidism before exercise was 4.06±0.78%, which was significantly lower than that in control subjects (5.54±0.61%, p<0.001), and it improved markedly after 6 months of exercise (5.0±0.79, p<0.001). The absolute changes in OPG showed significant correlation with the changes in FMD (r= − 0.432, p=0.001), TBARS (r= − 0.370, p=0.004) and CRP (r= − 0.503, p<0.001).

Conclusion:

The current study demonstrates that plasma OPG levels increased significantly at baseline, decreased dramatically after 6 months regular aerobic exercise training, and are correlated with endothelium-dependent arterial dilation in HT patients with euthyroidism.

Clinical Trial Registration Number: No

Key words

Hashimoto’s thyroiditis - osteoprotegerin - endothelial dysfunction - exercise training

Full Text

References

References
1 Simonet WS, Lacey DL, Dunstan CR et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 1997; 89: 309-319
2 Hsu H, Lacey DL, Dunstan CR et al. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci USA 1999; 96: 3545-3549
3 Zhang J, Fu M, Myles D et al. PDGF induces osteoprotegerin expression in vascular smooth muscle cells by multiple signal pathways. FEBS letters 2002; 521: 180-184
4 Malyankar UM, Scatena M, Suchland KL et al. Osteoprotegerin is an а_vβ₃-induced, NF-kappa B-dependent survival factor for endothelial cells. Journal of Biology Chemistry 2000; 275: 20959- 20962
5 Jono S, Ikari Y, Shioi A et al. Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease. Circulation 2002; 106: 1192-1194
6 Schoppet M, Sattler AM, Schaefer JR et al. Increased osteoprotegerin serum levels in men with coronary artery disease. J Clin Endocrinol Metab 2003; 88: 1024-1028
7 Avignon A, Sultan A, Piot C et al. Osteoprotegerin is associated with silent coronary artery disease in high-risk but asymptomatic type 2 diabetic patients. Diabetes Care 2005; 28: 2176-2180
8 Ross R. The pathogenesis of atherosclerosis, an update. New England Journal of Medicine 1986; 8: 488-500
9 Bonetti PO, Lerman LO, Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arteriosclerosis Thrombosis and Vascular Biology 2003; 23: 168-175
10 Xiang GD, Sun HL, Cheng ZS et al. Changes in plasma concentration of osteoprotegerin before and after levothyroxine replacement therapy in hypothyroid patients. J Clin Endocrinol Metab 2005; 90: 5765-5768
11 Nagasaki T, Inaba M, Jono S et al. Increased levels of serum osteoprotegerin in hypothyroid patients and its normalization with restoration of normal thyroid function. Eur J Endocrinol 2005; 152: 347-353
12 Xiang GD, He YS, Zhao LS et al. Impairment of endothelium-dependent arterial dilation in Hashimoto’s thyroiditis patients with euthyroidism. Clinical Endocrinology 2006; 64: 698-702
13 Xiang GD, Wang YL. Regular aerobic exercise training improves endothelium – dependent artery dilation in patients with impaired fasting glucose. Diabetes Care 2004; 27: 801-802
14 Fuchsjager-Mayerl G, Pleiner J, Wiesinger GF et al. Exercise training improves vascular endothelial function in patients with type 1 diabetes. Diabetes Care 2002; 25: 1780-1795
15 Maiorana A, O’Driscoll G, Cheetham C et al. The effect of combined aerobic and resistance exercise training on vascular function in type 2 diabetes. Journal of the American College of Cardiology 2001; 38: 860-866
16 Rinder MR, Spina RJ, Ehsani AA. Enhanced endothelium-dependent vasodilation in older endurance-trained men. Journal of Applied Physiology 2000; 88: 761-766
17 Xiang GD, Pu JH, Sun HL et al. Regular aerobic exercise training improves endothelium-dependent arterial dilation in patients with subclinical hypothyroidism. European Journal of Endocrinology 2009; 161: 755-761
18 Kawano H, Motoyama T, Hirashima O et al. Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery. J Am Coll Cardiol 1999; 34: 146-154
19 Motoyama T, Kawano H, Kugiyama K et al. Vitamin E administration improves impairment of endothelium-dependent vasodilation in patients with coronary spastic angina. J Am Coll Cardiol 1998; 32: 1672-1679
20 Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol 1987; 52: 302-310
21 Xiang GD, Xu L, Zhao LS et al. The relationship between plasma osteoprotegerin and endothelium-dependent arterial dilation in type 2 diabetes. Diabetes 2006; 55: 2126-2131
22 Satter AM, Schoppet M, Schaefer JR et al. Novel aspects on RANK ligand and osteoprotegerin in osteoporosis and vascular disease. Calcif Tissue Int 2004; 74: 103-106
23 Emery JG, McDonnell P, Burke MB et al. Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem 1998; 273: 14363-14367
24 Kiechl S, Schett G, Wenning G et al. Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease. Circulation 2004; 109: 2175-2180
25 Bucay N, Sarosi I, Dunstan CR et al. Osteoprotegerin deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 1998; 12: 126-128
26 Min H, Morony S, Sarosi I et al. Osteoprotegerin reverses osteoporosis by inhibiting endosteal osteoclasts and prevents vascular calcification by blocking a process resembling osteoclastogenesis. J Exp Med 2000; 192: 463-474
27 Price PA, June HH, Buckley JR et al. Osteoprotegerin inhibits artery calcification induced by warfarin and by vitamin D. Arterioscler Thromb Vasc Biol 2001; 21: 1610-1616
28 Ovchinnikova O, Gylfe A, Bailey L et al. Osteoprotegerin promotes fibrous cap formation in atherosclerotic lesions of apoE-deficient mice-brief report. Arterioscler Thromb Vasc Biol 2009; 29: 1478-1480
29 Kobayashi-Sakamoto M, Hirose K, Nishikata M et al. Osteoprotegerin protects endothelial cells against apoptotic cell death induced by porphyromonas gingivalis cysteine proteinases. FEMS Microbiol Lett 2006; 264: 238-245
30 Browner WS, Lui LY, Cummings SR. Association of serum osteoprotegerin levels with diabetes, stroke, bone density, fracture, and mortality in elderly women. J Clin Endocrinol Metab 2001; 86: 631-637
31 Mogelvang R, Pedersen SH, Flyvbjerg A et al. Comparison of osteoprotegerin to traditional atherosclerotic risk factors and high-sensitivity C-reactive protein for diagnosis of atherosclerosis. Am J Cardiol 2012; 109: 515-520
32 Hofbauer LC, Schoppet M. Osteoprotegerin: a link between osteoporosis and arterial calcification?. Lancet 2001; 358: 257-259
33 Papaioannou GI, Lagasse M, Mather JF et al. Treating hypothyroidism improves endothelial function. Metabolism 2004; 53: 278-279
34 Taddei S, Caraccio N, Virdis A et al. Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism: beneficial effect of levothyroxine therapy. J Clin Endocrinol Metab 2003; 88: 3731-3737
35 Xiang GD, Sun HL, Zhao LS. Changes of osteoprotegerin before and after insulin therapy in type 1 diabetic patients. Diabet Res Clin Pract 2007; 76: 199-206
36 Kim SM, Leet J, Ryu OH et al. Serum osteoprotegerin levels are associated with inflammation and pulse wave velocity. Clin Endocrinol 2006; 63: 594-598
37 Xiang GD, Pu JH, Sun HL et al. Alpha-lipoic acid improves endothelial dysfunction in patients with subclinical hypothyroidism. Exp Clin Endocrinol Diabetes 2010; 118: 625-629