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      The relationship between apelin and cardiac parameters in patients on peritoneal dialysis: is there a new cardiac marker?

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          Abstract

          Background

          Many markers have been proposed for CVD risk assessment in dialysis population. Apelin is a peptide that has roles in cardiovascular functions and volume regulation namely vasodilation, decreased blood pressure (BP), positive inotropic effect and inhibition of antidiuretic hormone release. The aim of this study was to examine relationship of apelin levels with echocardiographic findings and laboratory parameters related with cardiovascular function and bone mineral metabolism among peritoneal dialysis (PD) patients.

          Methods

          This is a cross-sectional study in which chronic PD patients aged between 18 and 80 without active cardiac, infectious or malignant diseases and hypervolemia have been included. Apelin-36 levels and echocardiographic findings were recorded as well as clinical and laboratory data.

          Results

          Of the 53 patients, the mean age and female/male ratio was 52.8 ± 15.3 years and 30/23, respectively. Mean apelin level was 1.45 ± 0.37 ng/ml. Gender, drugs (renin-angiotensin-aldosteron inhibitors, statins), presence of left ventricular hypertrophy, diabetes mellitus, hypertension, hyperlipidemia and significant residual renal function did not affect apelin-36 levels. Apelin-36 was correlated negatively with age and left atrium diameter; and positively with diastolic BP, ejection fraction (EF), total cholesterol, LDL-cholesterol, HDL-cholesterol, parathyroid hormone and alkaline phosphatase (ALP) levels. Diastolic BP, LDL-cholesterol, ALP and EF were found to be the independent determinants of apelin-36 levels with linear regression analysis.

          Conclusions

          Apelinergic system has important roles in volume regulation, cardiovascular functions, lipid metabolism and bone mineral disorders in PD patients. Prospective studies with large population are required.

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          Most cited references29

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          A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11.

          We report the cloning of a gene, intronless in its coding region, which we have named APJ. This gene was cloned using the polymerase chain reaction (PCR), with a set of primers designed on the basis of the conservation that members of G protein-coupled receptors (GPCR) have in their transmembrane (TM) regions. The putative receptor protein, APJ, shares closest identity to the angiotensin receptor (AT1) ranging from 40 to 50% in the hydrophobic TM regions of these receptors. The transcripts for this gene were detected in many regions of the brain. PCR analysis of somatic cell lines found APJ-related sequences to be only present on chromosome 11, and high-resolution mapping by fluorescence in situ hybridization (FISH) sublocalized APJ on band q12.
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            The novel peptide apelin lowers blood pressure via a nitric oxide-dependent mechanism.

            Apelin is an endogenous ligand of the human orphan receptor APJ. We detected apelin-like immunoreactivity in the adipocytes, gastric mucosa, and Kupffer cells in the liver. We also detected apelin-like immunoreactivity localized within the endothelia of small arteries in various organs. Further, it was found that mean arterial pressure after the administration of apelin-12, apelin-13, and apelin-36 at a dose of 10 nmol/kg in anaesthetized rats was reduced by 26+/-5, 11+/-4, and 5+/-4 mm Hg, respectively. In the presence of a nitric oxide (NO) synthase inhibitor, the effect of apelin-12 on blood pressure was abolished. Furthermore, the administration of apelin-12 (10 nmol/kg) in rats produced a transitory elevation of the plasma nitrite/nitrate concentration from a basal level of 21.4+/-1.6 to 27.0+/-1.5 microM. Thus, apelin may lower blood pressure via a nitric oxide-dependent mechanism.
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              Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility.

              The orphan receptor APJ and its recently identified endogenous ligand, apelin, exhibit high levels of mRNA expression in the heart. However, the functional importance of apelin in the cardiovascular system is not known. In isolated perfused rat hearts, infusion of apelin (0.01 to 10 nmol/L) induced a dose-dependent positive inotropic effect (EC50: 33.1+/-1.5 pmol/L). Moreover, preload-induced increase in dP/dt(max) was significantly augmented (P<0.05) in the presence of apelin. Inhibition of phospholipase C (PLC) with U-73122 and suppression of protein kinase C (PKC) with staurosporine and GF-109203X markedly attenuated the apelin-induced inotropic effect (P<0.001). In addition, zoniporide, a selective inhibitor of Na+-H+ exchange (NHE) isoform-1, and KB-R7943, a potent inhibitor of the reverse mode Na+-Ca2+ exchange (NCX), significantly suppressed the response to apelin (P<0.001). Perforated patch-clamp recordings showed that apelin did not modulate L-type Ca2+ current or voltage-activated K+ currents in isolated adult rat ventricular myocytes. Apelin mRNA was markedly downregulated in cultured neonatal rat ventricular myocytes subjected to mechanical stretch and in vivo in two models of chronic ventricular pressure overload. The present study provides the first evidence for the physiological significance of apelin in the heart. Our results show that apelin is one of the most potent endogenous positive inotropic substances yet identified and that the inotropic response to apelin may involve activation of PLC, PKC, and sarcolemmal NHE and NCX.
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                Author and article information

                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central
                1471-2369
                2014
                16 January 2014
                : 15
                : 18
                Affiliations
                [1 ]Department of Nephrology, Haseki Training and Research Hospital, Adivar Caddesi, Aksaray, Fatih, Istanbul, Turkey
                [2 ]Istanbul Medical Faculty, Department of Cardiology, Istanbul University, Istanbul, Turkey
                [3 ]Department of Biochemistry, Haseki Training and Research Hospital, Istanbul, Turkey
                [4 ]Medical Faculty, Department of Nephrology, Bezmialem Vakif University, Istanbul, Turkey
                Article
                1471-2369-15-18
                10.1186/1471-2369-15-18
                3930824
                24433492
                d7870a43-5ee4-4ae8-81f9-89f1cb552b3a
                Copyright © 2014 Karadag et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 July 2012
                : 25 November 2013
                Categories
                Research Article

                Nephrology
                apelin,hypervolemia,echocardiography,peritoneal dialysis
                Nephrology
                apelin, hypervolemia, echocardiography, peritoneal dialysis

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