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      Association of serum angiopoietin-1, angiopoietin-2 and angiopoietin-2 to angiopoietin-1 ratio with heart failure in patients with acute myocardial infarction

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          Abstract

          The aim of the present study was to investigate the association of the serum angiopoietin (Ang)-1 and Ang-2 levels and the Ang-2 to Ang-1 ratio (Ang-2/Ang-1) with heart failure (HF) in patients with acute myocardial infarction (AMI) during hospitalization. The serum Ang-1 and Ang-2 levels of the AMI patients were measured at admission to hospital. The correlations between serum Ang-1, Ang-2 and Ang-2/Ang-1 with HF were examined. Among 103 patients, 20 developed HF during hospitalization. The serum Ang-2 level and Ang-2/Ang-1 were found to be significantly higher in the patients with HF than in the patients without HF (2,203.1±122.0 vs. 2,102.3±114.4 pg/ml, P=0.001 and 11.4±1.6×10 −2 vs. 10.6±1.1×10 −2, P=0.007, respectively). Serum Ang-2 level and Ang-2/Ang-1 were negatively correlated with left ventricular ejection fraction (LVEF; r=−0.352, P<0.001 and r=−0.365, P<0.001, respectively) and positively correlated with the natural logarithm of the level of N-terminal pro-B-type natriuretic peptide (LnNT-proBNP, r=0.367, P<0.001 and r=0.304, P=0.003, respectively) and peak cardiac troponin T (cTnT, r=0.421, P<0.001 and r=0.278, P=0.009, respectively). However, the serum Ang-1 level was not found to correlate significantly with LVEF (r= 0.194, P= 0.05), LnNT-proBNP (r=−0.116, P=0.266) or peak cTnT (r=−0.056, P=0.607). In multivariable logistic regression analysis, Ang-2 (P=0.031), Ang-2/Ang-1 (P=0.018) and NT-proBNP (P=0.001) were revealed to be independently associated with HF. The present study reveals that Ang-2 levels and Ang-2/Ang-1 are independent predictors of HF in AMI patients during hospitalization.

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          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.
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            Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation.

            The angiopoietins Ang-1 and Ang-2 have been identified as ligands of the receptor tyrosine kinase Tie-2 (refs. 1,2). Paracrine Ang-1-mediated activation of Tie-2 acts as a regulator of vessel maturation and vascular quiescence. In turn, the antagonistic ligand Ang-2 acts by an autocrine mechanism and is stored in endothelial Weibel-Palade bodies from where it can be rapidly released upon stimulation. The rapid release of Ang-2 implies functions of the angiopoietin-Tie system beyond its established role during vascular morphogenesis as a regulator of rapid vascular responses. Here we show that mice deficient in Ang-2 (encoded by the gene Angpt2) cannot elicit an inflammatory response in thioglycollate-induced or Staphylococcus aureus-induced peritonitis, or in the dorsal skinfold chamber model. Recombinant Ang-2 restores the inflammation defect in Angpt2(-/-) mice. Intravital microscopy showed normal TNF-alpha-induced leukocyte rolling in the vasculature of Angpt2(-/-)mice, but rolling cells did not firmly adhere to activated endothelium. Cellular experiments showed that Ang-2 promotes adhesion by sensitizing endothelial cells toward TNF-alpha and modulating TNF-alpha-induced expression of endothelial cell adhesion molecules. Together, these findings identify Ang-2 as an autocrine regulator of endothelial cell inflammatory responses. Ang-2 thereby acts as a switch of vascular responsiveness exerting a permissive role for the activities of proinflammatory cytokines.
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              Pathogenesis of myocardial ischemia-reperfusion injury and rationale for therapy.

              Since the initial description of the phenomenon by Jennings et al 50 years ago, our understanding of the underlying mechanisms of reperfusion injury has grown significantly. Its pathogenesis reflects the confluence of multiple pathways, including ion channels, reactive oxygen species, inflammation, and endothelial dysfunction. The purposes of this review are to examine the current state of understanding of ischemia-reperfusion injury, as well as to highlight recent interventions aimed at this heretofore elusive target. In conclusion, despite its complexity our ongoing efforts to mitigate this form of injury should not be deterred, because nearly 2 million patients annually undergo either spontaneous (in the form of acute myocardial infarction) or iatrogenic (in the context of cardioplegic arrest) ischemia-reperfusion. Copyright (c) 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Exp Ther Med
                Exp Ther Med
                ETM
                Experimental and Therapeutic Medicine
                D.A. Spandidos
                1792-0981
                1792-1015
                March 2013
                14 January 2013
                14 January 2013
                : 5
                : 3
                : 937-941
                Affiliations
                Department of Cardiology, Peking University Third Hospital; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, P.R. China
                Author notes
                Correspondence to: Dr Baoxia Chen, Department of Cardiology, Peking University Third Hospital, 49 Huayuan-Bei Road, Beijing 100191, P.R. China, E-mail: changhongliangcn@ 123456yeah.net
                Article
                etm-05-03-0937
                10.3892/etm.2013.893
                3570239
                23408510
                ef327bb1-d515-4555-9f5d-7782ce6fb0db
                Copyright © 2013, Spandidos Publications

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

                History
                : 21 November 2012
                : 02 January 2013
                Categories
                Articles

                Medicine
                acute myocardial infarction,angiopoietin,heart failure
                Medicine
                acute myocardial infarction, angiopoietin, heart failure

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