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      What Is the Role of Apelin regarding Cardiovascular Risk and Progression of Renal Disease in Type 2 Diabetic Patients with Diabetic Nephropathy?

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          Abstract

          Aims. To evaluate the association of different apelin levels with cardiovascular mortality, hospitalization, renal function, and cardiovascular risk factors in type 2 diabetic patients with mild to moderate CKD. Methods. An observational, prospective study involving 150 patients divided into groups according to baseline apelin levels: 1 ≤ 98 pg/mL, 2 = 98–328 pg/mL, and 3 ≥ 329 pg/mL. Baseline characteristics were analyzed and compared. Multivariate Cox regression was used to find out predictors of cardiovascular mortality, and multivariate logistic regression was used to find out predictors of hospitalization and disease progression. Simple linear regressions and Pearson correlations were used to investigate correlations between apelin and renal disease and cardiovascular risk factors. Results. Patients' survival at 83 months in groups 1, 2, and 3 was 39%, 40%, and 71.2%, respectively ( P = 0.046). Apelin, age, and eGFR were independent predictors of mortality, and apelin, creatinine, eGFR, resistin, and visfatin were independent predictors of hospitalization. Apelin levels were negatively correlated with cardiovascular risk factors and positively correlated with eGFR. Patients with lower apelin levels were more likely to start a depurative technique. Conclusions. Apelin levels might have a significant clinical use as a marker/predictor of cardiovascular mortality and hospitalization or even as a therapeutic agent for CKD patients with cardiovascular disease.

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          Most cited references9

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          The role of apelin in cardiovascular function and heart failure.

          Apelin is a novel peptide that acts through the APJ receptor, sharing similarities with the angiotensin II-angiotensin II type 1 receptor pathway. It is a peripheral vasodilator, powerful inotrope and may affect central fluid homeostasis. Animal and human studies suggest that it may play a role in the pathogenesis of heart failure by modulating the harmful effects of angiotensin II. Apelin is reduced in patients with heart failure and up regulated following favourable left ventricular remodelling. It is widely distributed in a number of tissues, mainly restricted to vascular endothelium. This comprehensive review of the literature highlights the important studies that have led to the discovery of apelin and its role in cardiovascular function and heart failure.
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            Metabolic actions of adipocyte hormones: focus on adiponectin.

            The obesity epidemic has focused attention on the endocrine function of adipose tissue. Adipose tissue secretes leptin, cytokines, complement factors, and components of the coagulation cascade, most of which are increased in obesity. In contrast, a strong negative correlation exists between adiponectin and adiposity, insulin sensitivity, diabetes, vascular inflammation, and atherosclerosis. Adiponectin treatment in rodents increases insulin sensitivity and reduces lipids and atherogenesis. Chronic and central adiponectin treatment reduces weight, glucose, and lipids. The insulin-sensitizing action of thiazolidinediones is mediated, in part, through adiponectin. A causal role of adiponectin in diabetes, dyslipidemia, and atherosclerosis has been established in knockout mice. Therefore, adiponectin seems to be a marker of obesity-related diseases and a potential therapeutic target.
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              Effects of adipocyte-derived cytokines on endothelial functions: implication of vascular disease.

              Adipose tissue has recently emerged as an active endocrine organ that secretes a variety of metabolically important substances, collectively called adipocytokines or adipokines. In this review we summarize the effects of the adipokines leptin, adiponectin, and resistin on the vasculature and their potential role for pathogenesis of vascular disease. Leptin is associated with arterial wall thickness, decreased vessel distensibility, and elevated C reactive protein (CRP) levels. Leptin possesses procoagulant and antifibrinolytic properties, and it promotes thrombus and atheroma formation, probably through the leptin receptors by promoting vascular inflammation, proliferation, and calcification, and by increasing oxidative stress. Research for development of pharmacologic antagonism for the leptin receptor is currently under way. Adiponectin inhibits the expression of the adhesion molecules ICAM-1, VCAM-1, and P selectin. Therefore, it interferes with monocyte adherence to endothelial cells and their subsequent migration to the subendothelial space, one of the initial events in the development of atherosclerosis. Adiponectin also inhibits the transformation of macrophages to foam cells in vitro and decreases their phagocytic activity. Resistin, discovered in 2001, represents the newest of the adipokines and was named for its ability to promote insulin resistance. Resistin increases the expression of the adhesion molecules VCAM-1 and ICAM-1, up-regulates the monocyte chemoattractant chemokine-1, and promotes endothelial cell activation via ET-1 release. Although many aspects of its function need further clarification, it appears that resistin will add significantly to our knowledge of the pathophysiology of vascular disease and the metabolic syndrome.
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                Author and article information

                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi Publishing Corporation
                2314-6133
                2314-6141
                2013
                9 September 2013
                : 2013
                : 247649
                Affiliations
                1Nephrology Department, Hospital Faro, Rua Leão Penedo, 8000-386 Faro, Portugal
                2Pathology Clinic, Hospital Faro, 8000-836 Faro, Portugal
                3Science of the Sea Department, University of Algarve, 8000-140 Faro, Portugal
                4Cardiology Department, Hospital Faro, 8000-386 Faro, Portugal
                5Pharmacology Department, Gnostic Laboratory, 8000-307 Faro, Portugal
                Author notes

                Academic Editor: Denis Feliers

                Author information
                http://orcid.org/0000-0001-8218-8286
                Article
                10.1155/2013/247649
                3781832
                24089668
                49ea6455-fe69-4ecf-82e7-dd3e50503162
                Copyright © 2013 Ana Paula Silva 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
                : 30 April 2013
                : 5 August 2013
                : 8 August 2013
                Categories
                Research Article

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