Key result
Leflunomide antagonized cardiac hypertrophy, dysfunction, and fibrosis in mice and cultured cells via inhibition of Akt signaling.
Why the study?
Does leflunomide reduce cardiac hypertrophy in preclinical models?
Does leflunomide reduce cardiac hypertrophy in preclinical models?
Leflunomide, an anti-inflammatory drug, shows potential as a repurposed treatment for cardiac hypertrophy by inhibiting Akt signaling.
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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Pescatore et al. (2018) conducted an editorial in Cardiac hypertrophy. Leflunomide was evaluated on Cardiac hypertrophy, dysfunction, and fibrosis. Leflunomide antagonized cardiac hypertrophy, dysfunction, and fibrosis in mice and cultured cells via inhibition of Akt signaling.
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