Studies have indicated that dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists reduce infarct size after myocardial ischaemia. Whether these agents modify cardiac remodelling after ischaemia is unclear. Furthermore, it is not known if combination of the two types of drugs is superior to either agent alone. We investigated the modulatory effect of the DPP-4 inhibitor linagliptin alone, the GLP-1 activator liraglutide alone, or the two agents together on myocardial infarct size, left ventricular contractile function and cardiac remodelling signals after a brief period of left coronary artery (LCA) occlusion. C57BL/6 mice were treated with vehicle, the DPP-4 inhibitor linagliptin, the GLP-1 activator liraglutide, or both agents together for 5 days, and then subjected to LCA occlusion (1 h) and reperfusion (3 h). Ischaemia–reperfusion increased reactive oxygen species (ROS) generation and expression of NADPH oxidase (p47phox, p22phox and gp91phox subtypes), collagens, fibronectin and proinflammatory cytokines (interleukin 6, tumour necrosis factor α and monocyte chemoattractant protein-1) in the LCA-supplied regions. Pre-treatment with linagliptin or liraglutide reduced infarct size, protected cardiomyocytes from injury and preserved cardiac contractile function in a similar fashion. It is interesting that profibrotic (collagen deposition) signals were expressed soon after ischaemia–reperfusion. Both linagliptin and liraglutide suppressed ROS generation, NADPH oxidase and proinflammatory signals, and reduced collagen deposition. Addition of linagliptin or liraglutide had no significant additive effect above and beyond that of liraglutide and linagliptin given alone. In conclusion, linagliptin and liraglutide can improve cardiac contractile function and indices of cardiac remodelling, which may be related to their role in inhibition of ROS production and proinflammatory cytokines after ischaemia.
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August 2016
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GABAB receptor-mediated hypertension via hyperpolarization of solitary tract nucleus neurons that receive and integrate baroreceptor afferent inputs. See pp. 1417-1434 for further details. Image kindly provided by Omar Logue
Research Article|
June 29 2016
Modulation of myocardial injury and collagen deposition following ischaemia–reperfusion by linagliptin and liraglutide, and both together
Xianwei Wang;
Xianwei Wang
*Central Arkansas Veterans Healthcare System, and the Division of Cardiology, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A.
†Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, Henan, China
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Zufeng Ding;
Zufeng Ding
*Central Arkansas Veterans Healthcare System, and the Division of Cardiology, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A.
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Fen Yang;
Fen Yang
†Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, Henan, China
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Yao Dai;
Yao Dai
*Central Arkansas Veterans Healthcare System, and the Division of Cardiology, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A.
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Peng Chen;
Peng Chen
†Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, Henan, China
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Sue Theus;
Sue Theus
*Central Arkansas Veterans Healthcare System, and the Division of Cardiology, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A.
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Sharda Singh;
Sharda Singh
*Central Arkansas Veterans Healthcare System, and the Division of Cardiology, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A.
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Madhu Budhiraja;
Madhu Budhiraja
*Central Arkansas Veterans Healthcare System, and the Division of Cardiology, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A.
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Jawahar L. Mehta
*Central Arkansas Veterans Healthcare System, and the Division of Cardiology, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A.
Correspondence: Jawahar L. Mehta (email [email protected]).
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Publisher: Portland Press Ltd
Received:
January 27 2016
Revision Received:
April 12 2016
Accepted:
April 26 2016
Accepted Manuscript online:
April 26 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2016
Clin Sci (Lond) (2016) 130 (15): 1353–1362.
Article history
Received:
January 27 2016
Revision Received:
April 12 2016
Accepted:
April 26 2016
Accepted Manuscript online:
April 26 2016
Citation
Xianwei Wang, Zufeng Ding, Fen Yang, Yao Dai, Peng Chen, Sue Theus, Sharda Singh, Madhu Budhiraja, Jawahar L. Mehta; Modulation of myocardial injury and collagen deposition following ischaemia–reperfusion by linagliptin and liraglutide, and both together. Clin Sci (Lond) 1 August 2016; 130 (15): 1353–1362. doi: https://doi.org/10.1042/CS20160061
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