Cardiac hypertrophy (CH) is a major independent risk factor for heart failure and mortality. However, therapeutic interventions that target hypertrophy signaling in a load-independent way are unavailable. In a recent issue of Clinical Science (vol. 132, issue 6, 685-699), Ma et al. describe that the anti-inflammatory drug leflunomide markedly antagonized CH, dysfunction, and fibrosis induced by aortic banding or angiotensin-II in mice or by agonists in cultured cells. Unexpectedly, this occurred not via anti-inflammatory mechanisms but rather via inhibtion of Akt (protein kinase B, PKB) signaling. We further discuss the mechanisms underlying Akt activation and its effects on CH and review possible mechanisms of leflunomide effects. Despite some caveats, the availability of such a newly repurposed compound to treat CH can be a relevant advance.
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May 2018
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Depiction of a macrophage. In issue 9 of Clinical science, Liu et al. discuss the role of miRNAs in alveolar macrophage activation; for details see pages 943–958.
Commentary|
May 25 2018
Leflunomide counterakts cardiac hypertrophy
Luciana A. Pescatore;
Luciana A. Pescatore
*
1Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil
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Francisco R.M. Laurindo
Francisco R.M. Laurindo
*
1Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil
Correspondence: Francisco R.M. Laurindo ([email protected])
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Publisher: Portland Press Ltd
Received:
April 18 2018
Revision Received:
April 20 2018
Accepted:
April 23 2018
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (10): 1069–1073.
Article history
Received:
April 18 2018
Revision Received:
April 20 2018
Accepted:
April 23 2018
Connected Content
This is a commentary on:
A77 1726 (leflunomide) blocks and reverses cardiac hypertrophy and fibrosis in mice
Citation
Luciana A. Pescatore, Francisco R.M. Laurindo; Leflunomide counterakts cardiac hypertrophy. Clin Sci (Lond) 31 May 2018; 132 (10): 1069–1073. doi: https://doi.org/10.1042/CS20180228
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