For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
14
views
31
references
 Top references
cited by
73
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
1 collections
    0
    shares
      223
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found

      Ibuprofen Attenuates Cardiac Fibrosis in Streptozotocin-Induced Diabetic Rats

      research-article

      Read this article at

      ScienceOpenPublisherPubMed
      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

          Objective: To investigate the effects of ibuprofen on cardiac fibrosis in a rat model of type 1 diabetes. Methods: The diabetic model was established by injecting streptozotocin into the rats. Then, ibuprofen or pioglitazone was given by gavage for 8 weeks. The cardiac fibrosis was assessed, and the major components of the renin-angiotensin system, the transforming growth factor β<sub>1</sub> (TGF-β<sub>1</sub>) and the mammalian target of rapamycin (mTOR), were evaluated by histopathological, immunohistochemical, Western blot analysis or ELISA assay. Results: Obvious cardiac fibrosis was detected in the diabetic group and was alleviated by ibuprofen treatment. Angiotensin-converting enzyme (ACE), angiotensin (Ang) II and AngII type 1 receptor (AT1-R) levels were higher, and ACE2, Ang(1-7) and Mas receptor (Mas-R) were lower in the diabetic group. The ratio of ACE to ACE2 was raised in the diabetic group. All these changes were ameliorated by ibuprofen. TGF-β<sub>1</sub> and mTOR were raised in the hearts of the diabetic group and were attenuated by ibuprofen treatment. There was no significant difference between the ibuprofen and the pioglitazone groups. Conclusion: Ibuprofen could ameliorate the cardiac fibrosis in diabetic rats by reduction of the ACE/AngII/AT1-R axis and enhancement of the ACE2/Ang(1-7)/Mas-R axis, leading to a decrease in TGF-β<sub>1</sub> and mTOR.

          Related collections

          Most cited references31

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

          Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications.

          Zhi Fang, Johannes B. Prins, Thomas H. Marwick (2004)
          The presence of a diabetic cardiomyopathy, independent of hypertension and coronary artery disease, is still controversial. This systematic review seeks to evaluate the evidence for the existence of this condition, to clarify the possible mechanisms responsible, and to consider possible therapeutic implications. The existence of a diabetic cardiomyopathy is supported by epidemiological findings showing the association of diabetes with heart failure; clinical studies confirming the association of diabetes with left ventricular dysfunction independent of hypertension, coronary artery disease, and other heart disease; and experimental evidence of myocardial structural and functional changes. The most important mechanisms of diabetic cardiomyopathy are metabolic disturbances (depletion of glucose transporter 4, increased free fatty acids, carnitine deficiency, changes in calcium homeostasis), myocardial fibrosis (association with increases in angiotensin II, IGF-I, and inflammatory cytokines), small vessel disease (microangiopathy, impaired coronary flow reserve, and endothelial dysfunction), cardiac autonomic neuropathy (denervation and alterations in myocardial catecholamine levels), and insulin resistance (hyperinsulinemia and reduced insulin sensitivity). This review presents evidence that diabetes is associated with a cardiomyopathy, independent of comorbid conditions, and that metabolic disturbances, myocardial fibrosis, small vessel disease, cardiac autonomic neuropathy, and insulin resistance may all contribute to the development of diabetic heart disease.
          Article 0 comments Cited 212 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Myocardial cell death in human diabetes.

            A Frustaci, P Anversa, J Kajstura … (2000)
            The renin-angiotensin system is upregulated with diabetes, and this may contribute to the development of a dilated myopathy. Angiotensin II (Ang II) locally may lead to oxidative damage, activating cardiac cell death. Moreover, diabetes and hypertension could synergistically impair myocardial structure and function. Therefore, apoptosis and necrosis were measured in ventricular myocardial biopsies obtained from diabetic and diabetic-hypertensive patients. Accumulation of a marker of oxidative stress, nitrotyrosine, and Ang II labeling were evaluated quantitatively. The diabetic heart showed cardiac hypertrophy, cavitary dilation, and depressed ventricular performance. These alterations were more severe with diabetes and hypertension. Diabetes was characterized by an 85-fold, 61-fold, and 26-fold increase in apoptosis of myocytes, endothelial cells, and fibroblasts, respectively. Apoptosis in cardiac cells did not increase additionally with diabetes and hypertension. Diabetes increased necrosis by 4-fold in myocytes, 9-fold in endothelial cells, and 6-fold in fibroblasts. However, diabetes and hypertension increased necrosis by 7-fold in myocytes and 18-fold in endothelial cells. Similarly, Ang II labeling in myocytes and endothelial cells increased more with diabetes and hypertension than with diabetes alone. Nitrotyrosine localization in cardiac cells followed a comparable pattern. In spite of the difference in the number of nitrotyrosine-positive cells with diabetes and with diabetes and hypertension, apoptosis and necrosis of myocytes, endothelial cells, and fibroblasts were detected only in cells containing this modified amino acid. In conclusion, local increases in Ang II with diabetes and with diabetes and hypertension may enhance oxidative damage, activating cardiac cell apoptosis and necrosis.
            Article 0 comments Cited 161 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Angiotensin II and inflammation: the effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade.

              S Dhindsa, P Dandona, H Ghanim … (2006)
              Angiotensin II (Ang II) increases adhesion molecules, cytokines and chemokines and exerts a proinflammatory effect on leucocytes, endothelial cells and vascular smooth muscle cells. Acting via the type 1 receptor, Ang II initiates an inflammatory cascade of reduced nicotinamide-adenine dinucleotide phosphate oxidase, reactive oxygen species (ROS) and nuclear factor-kappaB, which mediates transcription and gene expression and increases adhesion molecules and chemokines. An excess of ROS decreases nitric oxide bioavailability, causes endothelial dysfunction, and promotes atherosclerosis. Moreover, Ang II interrupts the anti-inflammatory effects of insulin. Together, these effects promote a prothrombotic state as well as plaque rupture. Ang II receptor blockers suppress mediators of inflammation, including ROS and C-reactive protein, and they increase expression of inhibitory kappaB (an inhibitor of nuclear factor-kappaB). These anti-inflammatory and antioxidative effects, which are probably due in part to unopposed stimulation of the Ang II type 2 receptor, may be beneficial in acute coronary syndromes and may also contribute to the prevention of type II diabetes mellitus, as insulin resistance is mediated by inflammatory processes.
              Article 0 comments Cited 113 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (publisher-id): CRD
                Journal ID (nlm-ta): Cardiology
                Journal ID (doi): 10.1159/issn.0008-6312
                Title: Cardiology
                Publisher: S. Karger AG
                ISSN (Print): 0008-6312
                ISSN (Electronic): 1421-9751
                Publication date Subscription-year: 2015
                Publication date (Print): May 2015
                Publication date (Electronic): 15 April 2015
                Volume: 131
                Issue: 2
                Pages: 97-106
                Affiliations
                aJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, and bKey Laboratory of New Drugs and Clinical Application and cDepartment of Physiology, Xuzhou Medical College, and dDepartment of Cardiology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China
                Author notes
                *Xiaoxing Yin, PhD, Department of Clinical Pharmacology, School of Pharmacy, Xuzhou Medical College, No. 209 Tongshan Road, Xuzhou, Jiangsu 221004 (China), E-Mail yinxx@xzmc.edu.cn, Gang Hu, PhD, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029 (China), E-Mail ghu@njmu.edu.cn
                Author information
                https://orcid.org/0000-0001-9629-0644
                Article
                Publisher ID: 375362 Other ID: Cardiology 2015;131:97-106
                DOI: 10.1159/000375362
                PubMed ID: 25896805
                SO-VID: 08ee9ab1-5ec2-41ff-b12a-574a15e0857e
                Copyright © © 2015 S. Karger AG, Basel
                License:

                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.

                History
                Date received : 18 June 2014
                Date accepted : 16 January 2015
                Page count
                Figures: 6, Tables: 1, References: 39, Pages: 10
                Categories
                Subject: Original Research

                ScienceOpen disciplines: General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
                Keywords: Angiotensin-converting enzyme 2,Angiotensin-converting enzyme,Cardiac fibrosis,Ibuprofen,Diabetes
                Data availability:
                ScienceOpen disciplines: General medicine, Neurology, Cardiovascular Medicine, Internal medicine, Nephrology
                Keywords: Angiotensin-converting enzyme 2, Angiotensin-converting enzyme, Cardiac fibrosis, Ibuprofen, Diabetes

                Comments

                Comment on this article

                scite_

                Similar content223

                See all similar

                Cited by73

                See all cited by

                Most referenced authors378

                See all reference authors