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      The relationship between asymptomatic organ damage, and serum soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and Interleukin-17A (IL-17A) levels in non-diabetic hypertensive patients

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          Abstract

          Background

          This study aimed to measure the serum soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and interleukin-17A (IL-17A) levels in hypertensive patients with/without asymptomatic organ damage (AOD), as well as to determine the relationship between the serum sTWEAK and IL17-A levels, and carotid intima media thickness (CIMT), proteinuria, retinopathy, and the left ventricle mass index (LVMI).

          Methods

          The study included 159 patients diagnosed with and followed-up for primary hypertension (HT); 79 of the patients had AOD (61 female and 18 male) and 80 did not (52 female and 28 male). sTWEAK and IL-17A levels were measured in all patients.

          Results

          The sTWEAK level was significantly lower in the patients with AOD than in those without AOD (858.4 pg/mL vs. 1151.58 pg/mL, P = 0.001). The sTWEAK level was negatively correlated with the mean microalbuminuria level and LVMI. The median IL-17A level was significantly higher in the patients with AOD than in those without AOD (2.34 pg/mL vs. 1.80 pg/mL, P = 0.001). There was a positive correlation between mean IL-17A level, and mean microalbuminuria level, CIMT, and LVMI. Multivariate logistic regression analysis showed that patient age, sTWEAK level, and mean 24-h systolic blood pressure were predictors of AOD.

          Conclusions

          The sTWEAK level was lower and IL-17A level was higher in the patients with AOD. It remains unknown if sTWEAK and IL-17A play a role in the pathophysiology of AOD. Prospective observational studies are needed to determine the precise role of sTWEAK and IL-17A in the development of target organ damage.

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          Most cited references31

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          Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging.

          A study in vitro of specimens of human aortic and common carotid arteries was carried out to determine the feasibility of direct measurement (i.e., not from residual lumen) of arterial wall thickness with B mode real-time imaging. Measurements in vivo by the same technique were also obtained from common carotid arteries of 10 young normal male subjects. Aortic samples were classified as class A (relatively normal) or class B (with one or more atherosclerotic plaques). In all class A and 85% of class B arterial samples a characteristic B mode image composed of two parallel echogenic lines separated by a hypoechoic space was found. The distance between the two lines (B mode image of intimal + medial thickness) was measured and correlated with the thickness of different combinations of tunicae evaluated by gross and microscopic examination. On the basis of these findings and the results of dissection experiments on the intima and adventitia we concluded that results of B mode imaging of intimal + medial thickness did not differ significantly from the intimal + medial thickness measured on pathologic examination. With respect to the accuracy of measurements obtained by B mode imaging as compared with pathologic findings, we found an error of less than 20% for measurements in 77% of normal and pathologic aortic walls. In addition, no significant difference was found between B mode-determined intimal + medial thickness in the common carotid arteries evaluated in vitro and that determined by this method in vivo in young subjects, indicating that B mode imaging represents a useful approach for the measurement of intimal + medial thickness of human arteries in vivo.
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            Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction.

            We have shown previously that T cells are required for the full development of angiotensin II-induced hypertension. However, the specific subsets of T cells that are important in this process are unknown. T helper 17 cells represent a novel subset that produces the proinflammatory cytokine interleukin 17 (IL-17). We found that angiotensin II infusion increased IL-17 production from T cells and IL-17 protein in the aortic media. To determine the effect of IL-17 on blood pressure and vascular function, we studied IL-17(-/-) mice. The initial hypertensive response to angiotensin II infusion was similar in IL-17(-/-) and C57BL/6J mice. However, hypertension was not sustained in IL-17(-/-) mice, reaching levels 30-mm Hg lower than in wild-type mice by 4 weeks of angiotensin II infusion. Vessels from IL-17(-/-) mice displayed preserved vascular function, decreased superoxide production, and reduced T-cell infiltration in response to angiotensin II. Gene array analysis of cultured human aortic smooth muscle cells revealed that IL-17, in conjunction with tumor necrosis factor-alpha, modulated expression of >30 genes, including a number of inflammatory cytokines/chemokines. Examination of IL-17 in diabetic humans showed that serum levels of this cytokine were significantly increased in those with hypertension compared with normotensive subjects. We conclude that IL-17 is critical for the maintenance of angiotensin II-induced hypertension and vascular dysfunction and might be a therapeutic target for this widespread disease.
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              TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis.

              The members of the tumor necrosis factor (TNF) family play pivotal roles in the regulation of the immune system. Here we describe a new ligand in this family, designated TWEAK. The mouse and human versions of this protein are unusually conserved with 93% amino acid identity in the receptor binding domain. The protein was efficiently secreted from cells indicating that, like TNF, TWEAK may have the long range effects of a secreted cytokine. TWEAK transcripts were abundant and found in many tissues, suggesting that TWEAK and TRAIL belong to a new group of widely expressed ligands. Like many members of the TNF family, TWEAK was able to induce interleukin-8 synthesis in a number of cell lines. The human adenocarcinoma cell line, HT29, underwent apoptosis in the presence of both TWEAK and interferon-gamma. Thus, TWEAK resembles many other TNF ligands in the capacity to induce cell death; however, the fact that TWEAK-sensitive cells are relatively rare suggests that TWEAK along with lymphotoxins alpha/beta and possibly CD30L trigger death via a weaker, nondeath domain-dependent mechanism.
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                Author and article information

                Contributors
                dr.ihsanates@hotmail.com
                nihalozk@gmail.com
                ftm_dogru@hotmail.com
                cananyy@yahoo.com
                drserdarakyel@hotmail.com
                anurdanbarca@yahoo.com.tr
                fatded@yahoo.com
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                1 October 2014
                1 October 2014
                2014
                : 15
                : 1
                : 159
                Affiliations
                [ ]Department of Nephrology, Ankara Numune Education and Research Hospital, Sıhhiye, Ankara 061100 Turkey
                [ ]Biochemistry Department, Ankara Numune Education and Research Hospital, Sıhhiye, Ankara 061100 Turkey
                [ ]Cardiology Department, Ankara Numune Education and Research Hospital, Sıhhiye, Ankara 061100 Turkey
                [ ]Radiology Department, Ankara Numune Education and Research Hospital, Sıhhiye, Ankara 061100 Turkey
                Article
                848
                10.1186/1471-2369-15-159
                4190353
                25273526
                4c372fb9-f616-4415-b594-99a8774f8f9b
                © Ates et al.; licensee BioMed Central Ltd. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 7 July 2014
                : 29 September 2014
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2014

                Nephrology
                asymptomatic organ damage,hypertension,interleukin-17,tumor necrosis factor-like weak inducer of apoptosis

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