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      The Time Course of Tumor Necrosis Factor-α, Inducible Nitric Oxide Synthase and Vascular Endothelial Growth Factor Expression in an Experimental Model of Chronic Myocardial Infarction in Rats

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          Abstract

          An injury to the heart due to myocardial infarction may progress to heart failure. Among the cytokines and growth factors whose interactions promote remodeling of the heart, increased expression of tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) has been found. However, little is known about the sequence of gene expression during the progression of heart injury. In the present study, male Sprague-Dawley rats were used for experimental myocardial infarction performed by ligation of the left anterior descending coronary artery. TNF-α, iNOS and VEGF expression was assessed by reverse transcription polymerase chain reaction. Localization of TNF-α, VEGF and iNOS protein was assessed by immunohistochemistry. An in vitro proliferation (BrdU incorporation) and differentiation (tube formation) assay of human umbilical vein endothelial cells was performed. The expression of TNF-α, iNOS, VEGF<sub>164</sub> and VEGF<sub>188</sub> was observed during the whole period after myocardial infarction (on days 1, 4, 11, 28 and 40), whereas VEGF<sub>120</sub> was found only on day 1 and 4. The most intense immunostaining for TNF-α was observed at the border zone. The iNOS immunostaining was initially located in the endothelium, whereas later it was also present in the walls of larger vessels. The VEGF protein was present in the border zone. No gene expression or immunostaining was detected in sham-operated rats. The in vitro experiments showed both proangiogenic (low TNF-α concentration, short period of incubation) and antiangiogenic (high TNF-α concentration, long period of incubation) effects of TNF-α. The expression of TNF-α and iNOS genes with the concomitant occurrence of a decrease in VEGF<sub>120</sub>, VEGF<sub>188</sub> and VEGF<sub>164</sub> protein could be related to insufficient angiogenesis and may suggest the possible involvement of these events in remodeling after myocardial infarction.

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          Most cited references 7

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          Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.

          A new method of total RNA isolation by a single extraction with an acid guanidinium thiocyanate-phenol-chloroform mixture is described. The method provides a pure preparation of undegraded RNA in high yield and can be completed within 4 h. It is particularly useful for processing large numbers of samples and for isolation of RNA from minute quantities of cells or tissue samples.
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            Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188.

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              Phosphorylation and Activation of Myosin by Rho-associated Kinase (Rho-kinase)

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                Author and article information

                Journal
                JVR
                J Vasc Res
                10.1159/issn.1018-1172
                Journal of Vascular Research
                S. Karger AG
                1018-1172
                1423-0135
                2001
                June 2001
                25 May 2001
                : 38
                : 3
                : 288-300
                Affiliations
                aDepartment of Clinical Biochemistry CMUJ, Cracow, bDepartment of Pharmacology, Silesian School of Medicine, Zabrze, cDepartment of Pathomorphology, The Medical University of Warsaw, Warsaw, Poland
                Article
                51057 J Vasc Res 2001;38:288–300
                10.1159/000051057
                11399901
                © 2001 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 9, References: 58, Pages: 13
                Categories
                Research Paper

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