Leflunomide counter(akt)under-bars cardiac hypertrophy

Autor(es)

Pescatore, Luciana A. ; Laurindo, Francisco R. M.

• Tipo de documento: Artigo Científico
• Fonte: Clinical Science; v. 132, n. 10, p. 5-pg., 2018-05-31.

Resumo

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. (AU)

• Processo FAPESP: 15/25923-0 - Modulação da calcificação vascular pela dissulfeto isomerase proteica (PDI): estudo em um novo modelo de camundongo transgênico
• Beneficiário: Luciana Pescatore Alves
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs