50
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Urinary Angiopoietin-2 Is Associated with Albuminuria in Patients with Type 2 Diabetes Mellitus

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Aims. To evaluate the levels of angiopoietin-1 (Ang-1), Ang-2, and vascular endothelial growth factor (VEGF) in serum and urine, and their association with albuminuria in patients with type 2 diabetes mellitus. Methods. In 113 type 2 diabetic patients with normoalbuminuria, microalbuminuria, and macroalbuminuria and 30 healthy controls, the levels of Ang-1, Ang-2, and VEGF in serum and urine were measured by enzyme-linked immunosorbent assay (ELISA). Results. Urinary and serum levels of Ang-2 were significantly higher in diabetic patients with normoalbuminuria than in healthy controls. Increased urinary Ang-2 level was positively associated with the degree of albuminuria. Urinary Ang-1 levels were significantly higher in normoalbuminuria patients and lower in macroalbuminuria patients than in controls. The levels of urinary VEGF increased in the albuminuria subgroup, though serum levels of Ang-1 and VEGF did not change. Urinary Ang-2 levels were correlated positively with albuminuria and negatively with glomerular filtration rate (GFR). Stepwise multiple regression analysis identified albuminuria ( P < 0.001) and GFR ( P = 0.001) as significant predictors of urinary Ang-2. Conclusions. Our data suggest that urinary Ang-2 is stepwise increased with renal damage in patients with type 2 diabetes mellitus and is associated with albuminuria.

          Related collections

          Most cited references43

          • Record: found
          • Abstract: not found
          • Article: not found

          KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease.

          (2007)
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis.

            Angiogenesis is thought to depend on a precise balance of positive and negative regulation. Angiopoietin-1 (Ang1) is an angiogenic factor that signals through the endothelial cell-specific Tie2 receptor tyrosine kinase. Like vascular endothelial growth factor, Ang1 is essential for normal vascular development in the mouse. An Ang1 relative, termed angiopoietin-2 (Ang2), was identified by homology screening and shown to be a naturally occurring antagonist for Ang1 and Tie2. Transgenic overexpression of Ang2 disrupts blood vessel formation in the mouse embryo. In adult mice and humans, Ang2 is expressed only at sites of vascular remodeling. Natural antagonists for vertebrate receptor tyrosine kinases are atypical; thus, the discovery of a negative regulator acting on Tie2 emphasizes the need for exquisite regulation of this angiogenic receptor system.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Angiopoietin 2 is a partial agonist/antagonist of Tie2 signaling in the endothelium.

              Angiopoietin 2 (Ang2) was originally shown to be a competitive antagonist for Ang1 of the receptor tyrosine kinase Tie2 in endothelial cells (ECs). Since then, reports have conflicted on whether Ang2 is an agonist or antagonist of Tie2. Here we show that Ang2 functions as an agonist when Ang1 is absent but as a dose-dependent antagonist when Ang1 is present. Exogenous Ang2 activates Tie2 and the promigratory, prosurvival PI3K/Akt pathway in ECs but with less potency and lower affinity than exogenous Ang1. ECs produce Ang2 but not Ang1. This endogenous Ang2 maintains Tie2, phosphatidylinositol 3-kinase, and Akt activities, and it promotes EC survival, migration, and tube formation. However, when ECs are stimulated with Ang1 and Ang2, Ang2 dose-dependently inhibits Ang1-induced Tie2 phosphorylation, Akt activation, and EC survival. We conclude that Ang2 is both an agonist and an antagonist of Tie2. Although Ang2 is a weaker agonist than Ang1, endogenous Ang2 maintains a level of Tie2 activation that is critical to a spectrum of EC functions. These findings may reconcile disparate reports of Ang2's effect on Tie2, impact our understanding of endogenous receptor tyrosine kinase signal transduction mechanisms, and affect how Ang2 and Tie2 are targeted under conditions such as sepsis and cancer.
                Bookmark

                Author and article information

                Journal
                Int J Endocrinol
                Int J Endocrinol
                IJE
                International Journal of Endocrinology
                Hindawi Publishing Corporation
                1687-8337
                1687-8345
                2015
                19 March 2015
                : 2015
                : 163120
                Affiliations
                1Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, Hubei 430022, China
                2Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China
                Author notes

                Academic Editor: Giuseppina T. Russo

                Article
                10.1155/2015/163120
                4383519
                25873946
                fadd7302-d551-42a9-b024-b074c070c440
                Copyright © 2015 Shan Chen et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 June 2014
                : 8 September 2014
                : 18 September 2014
                Categories
                Research Article

                Endocrinology & Diabetes
                Endocrinology & Diabetes

                Comments

                Comment on this article