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CXCR4 Antagonism attenuates the development of diabetic cardiac fibrosis

Chu, Po-Yin, Walder, Ken, Horlock, Duncan, Williams, David, Nelson, Erin, Byrne, Melissa, Jandeleit-Dahm, Karin, Zimmet, Paul and Kaye, David M. 2015, CXCR4 Antagonism attenuates the development of diabetic cardiac fibrosis, PLoS One, vol. 10, no. 7, Article no: e0133616, pp. 1-13, doi: 10.1371/journal.pone.0133616.

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Title CXCR4 Antagonism attenuates the development of diabetic cardiac fibrosis
Author(s) Chu, Po-Yin
Walder, Ken
Horlock, Duncan
Williams, David
Nelson, Erin
Byrne, Melissa
Jandeleit-Dahm, Karin
Zimmet, Paul
Kaye, David M.
Journal name PLoS One
Volume number 10
Issue number 7
Season Article no: e0133616
Start page 1
End page 13
Total pages 13
Publisher Public Library of Science (PLOS)
Place of publication San Francisco, CA
Publication date 2015-07-27
ISSN 1932-6203
Summary Heart failure (HF) is an increasingly recognized complication of diabetes. Cardiac fibrosis is an important causative mechanism of HF associated with diabetes. Recent data indicate that inflammation may be particularly important in the pathogenesis of cardiovascular fibrosis. We sought to determine the mechanism by which cardiac fibrosis develops and to specifically investigate the role of the CXCR4 axis in this process. Animals with type I diabetes (streptozotocin treated mice) or type II diabetes (Israeli Sand-rats) and controls were randomized to treatment with a CXCR4 antagonist, candesartan or vehicle control. Additional groups of mice also underwent bone marrow transplantation (GFP+ donor marrow) to investigate the potential role of bone marrow derived cell mobilization in the pathogenesis of cardiac fibrosis. Both type I and II models of diabetes were accompanied by the development of significant cardiac fibrosis. CXCR4 antagonism markedly reduced cardiac fibrosis in both models of diabetes, similar in magnitude to that seen with candesartan. In contrast to candesartan, the anti-fibrotic actions of CXCR4 antagonism occurred in a blood pressure independent manner. Whilst the induction of diabetes did not increase the overall myocardial burden of GFP+ cells, it was accompanied by an increase in GFP+ cells expressing the fibroblast marker alpha-smooth muscle actin and this was attenuated by CXCR4 antagonism. CXCR4 antagonism was also accompanied by increased levels of circulating regulatory T cells. Taken together the current data indicate that pharmacological inhibition of CXCR4 significantly reduces diabetes induced cardiac fibrosis, providing a potentially important therapeutic approach.
Language eng
DOI 10.1371/journal.pone.0133616
Field of Research 110306 Endocrinology
Socio Economic Objective 920103 Cardiovascular System and Diseases
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, Public Library of Science (PLOS)
Persistent URL http://hdl.handle.net/10536/DRO/DU:30074833

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.