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Melatonin is a pineal-produced indole with a great cardioprotective capability against the development of diabetic cardiomyopathy.
We focused for the first time on melatonin-induced signalling mechanisms against diabetic cardiomyopathy.
Retinoid-related orphan receptor α was the key melatonin receptor conferring cardioprotection in diabetic heart.
Various molecules and signalling pathways, such as mammalian STE20‐like kinase 1 and endoplasmic reticulum-related axis, were further regulated by melatonin, which subsequently interrupt the progression of diabetic cardiomyopathy.
Melatonin is a pineal-produced indole known for its anti-aging, antiapoptotic and antioxidant properties. In past decades, the protective potentials of melatonin for cardiovascular diseases, such as atherosclerosis and myocardial infarction, have been widely revealed, triggering more investigations focused on other cardioprotective effects of melatonin. Recently, the roles of melatonin in diabetic cardiomyopathy (DCM) have attracted increased attention. In this regard, researchers found that melatonin attenuated cardiac fibrosis and hypertrophy, thus interrupting the development of DCM. Retinoid-related orphan receptor α is a key melatonin receptor that contributed to the cardioprotective effect of melatonin in hearts with DCM. For the downstream mechanisms, the inhibition of mammalian STE20‐like kinase 1 plays a pivotal role, which exerts antiapoptotic and proautophagic effects, thus enhancing cardiac tolerance in high-glucose conditions. In addition, other signalling mechanisms, such as sirtuin-1/peroxisome proliferator-activated receptor gamma-coactivator alpha and endoplasmic reticulum-related signalling, are also involved in the protective effects of melatonin on cardiomyocytes under diabetic conditions. This review will focus on the protective signalling mechanisms regulated by melatonin and provide a better understanding of the therapeutic applications of melatonin signalling in DCM.El texto completo de este artículo está disponible en PDF.
Abbreviations : DCM, I/R, CHD, AGEs, HG, ROS, AMPK, mTOR, SCG, PVN, NE, AANAT, HIOMT, RORα, NO, Nrf2, RISK, SAFE, Mst1, T1DM, Sirt1/3, PINK1, PGC-1α, SERCA2a, FoxO, Drp1, ER, UPR, PERK, TGF-β1, ATF-6, IRE1, CHOP, eIF2α, Syk, COX-I, ECM, mCFs, 3′UTRs, CTGF, VEGF
Keywords : Melatonin, Diabetic cardiomyopathy, Cardioprotection, Signalling mechanism, Antioxidation
Vol 128Artículo 110260- août 2020 Regresar al número
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