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      Osteoprotegerin concentration is associated with the presence and severity of peripheral arterial disease in type 2 diabetes mellitus Translated title: Osteoprotegerin concentration is associated with the presence and severity of peripheral arterial disease in type 2 diabetes mellitus

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          Abstract

          Abstract. Background: Osteoprotegerin plays a role in the development of several bone diseases. In addition, osteoprotegerin may contribute to the development of vascular disease. Little is known about the association between serum osteoprotegerin levels and the presence or severity of peripheral arterial disease (PAD). The aim of this study was to examine the association between serum osteoprotegerin levels and both the presence as well as the severity of lower extremity arterial disease in patients with type 2 diabetes (T2DM). Patients and methods: The study included 165 consecutive patients with T2DM (57 % males, mean age 65.0 ± 0.7 years). PAD was diagnosed by measurement of the toe-brachial index (TBI). Serum osteoprotegerin was measured using ELISA. Results: The mean osteoprotegerin level was significantly higher in patients with PAD in comparison to patients without PAD (18.2 ± 1.0 vs. 13.1 ± 2.0 pmol/L, p = 0.014). Significant univariate correlations between TBI and osteoprotegerin level (r = –0.308; p < 0.001), age, body mass index, and HDL cholesterol were observed. In the multivariate linear regression analysis, serum osteoprotegerin (β = –0.005; p = 0.020), higher age, and male gender were significant predictors of TBI. When 25(OH) vitamin D was introduced into the mentioned model, OPG was no longer a significant predictor of TBI and was replaced in the model with vitamin D (β = 0.009, p = 0.001). This finding suggests a role of OPG as a mediator of the effects of 25(OH) vitamin D. Conclusions: Serum osteoprotegerin level is significantly associated with both the presence and severity of PAD in patients with T2D. Osteoprotegerin might be a biomarker for the presence of atherosclerotic disease in patients with T2DM.

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          Most cited references42

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          2011 ACCF/AHA Focused Update of the Guideline for the Management of Patients With Peripheral Artery Disease (updating the 2005 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.

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            The osteoprotegerin/RANK/RANKL system: a bone key to vascular disease.

            Owing to the common coincidence of osteoporosis and vascular disease, pathophysiological links between both disorders have long been sought. The osteoprotegerin (OPG)/receptor activator of NF-kappaB (RANK)/receptor activator of NF-kappaB ligand (RANKL) cytokine network, a key regulatory system in bone homeostasis, has been implicated recently in vascular calcification, changes in matrix composition and diabetic macroangiopathy, aortic aneurysm development, heart failure and, most importantly, advanced atherosclerosis, plaque destabilization and manifestation of cardiovascular diseases. The concept of an active role of RANKL and OPG in vascular pathophysiology is intriguing and is gaining increasing support from both epidemiological and basic research. OPG serum level is considered to be a stable and reliable indicator of the overall activity of the OPG/RANK/RANKL axis and may find application as a biomarker of vascular risk and prognosis. RANKL in turn may be a suitable target for novel therapies. Pharmacological strategies for specific interference with the OPG/RANK/RANKL axis are currently being developed and evaluated in osteoporosis therapy.
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              Osteoprotegerin and osteopontin are expressed at high concentrations within symptomatic carotid atherosclerosis.

              The aim of this study was to compare the concentration of osteoprotegerin (OPG), receptor activator of nuclear factor kappaB ligand (RANKL), and osteopontin (OPN) in stable (asymptomatic) and unstable (symptomatic) carotid atherosclerosis. In addition, we were interested in the effect of angiotensin II blockade on the secretion of these proteins by unstable atherosclerosis. Endarterectomy samples removed from patients with recent (within 6 weeks) or no previous focal neurological symptoms were assessed by immunohistochemistry, Western analysis, and explant culture. Concentrations of OPG, RANKL, and OPN were measured by mean optical density (MOD), densitometry of protein bands, and enzyme-linked immunosorbent assay of supernatants from explant culture, and compared between symptomatic and asymptomatic patients. The concentration of OPG and OPN within the proximal internal carotid (PIC) part of the endarterectomy specimen removed from symptomatic patients was elevated 2- and 4-fold, respectively. Although the concentration of RANKL did not differ according to patients' symptoms, the quantity of OPG secreted by explants of the PIC was greater in explants from symptomatic patients and could be significantly reduced within 48 hours of incubation with the angiotensin II blocker irbesartan. OPG and OPN are upregulated in symptomatic human carotid atherosclerosis with possible implications for plaque stability. Angiotensin II blockade is able to downregulate OPG secretion in vitro.
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                Author and article information

                Contributors
                Journal
                vas
                VASA
                European Journal of Vascular Medicine
                Hogrefe AG, Bern
                0301-1526
                1664-2872
                January 09, 2018
                February 20, 2018
                : 47
                : 2
                : 131-135
                Affiliations
                [ 1 ]Department of Internal Medicine, Pavol Jozef Šafárik University, Faculty of Medicine, Louis Pasteur University Hospital, Košice, Slovakia
                [ a ]These authors contributed equally to this paper
                Author notes
                , Prof. Ivan Tkáč, M. D., Ph.D, Univerzita Pavla Jozefa Šafárika v Košiciach Lekárska fakulta, Rastislavova 43, 04190 Košice, Slovakia, E-mail ivan.tkac@ 123456upjs.sk
                Article
                vas_47_2_131
                10.1024/0301-1526/a000682
                68c67562-59e4-41be-8aaf-f9b94fead39e
                Copyright @ 2018
                History
                : November 6, 2017
                : November 25, 2017
                Categories
                Original communication

                Medicine
                type 2 diabetes mellitus,toe-brachial index,peripheral arterial disease,Osteoprotegerin

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