BET-inhibition by JQ1 alleviates streptozotocin-induced diabetic cardiomyopathy

Toxicology and Applied Pharmacology
Miao GuoWen-Jun Chen

Abstract

Diabetic cardiomyopathy is a cascade of complex events leading to eventual heart failure in diabetes. JQ1, one of Bromodomain and extra-terminal domain (BET) protein inhibitors, has exerted therapeutic effects on cancer proliferation, inflammation and cardiovascular disease. Recently, JQ1 was reported to protect mice from bleomycin-induced lung fibrosis and reverse the fibrotic response in carbon tetrachloride-induced liver fibrosis. However, its role in diabetic cardiomyopathy remains to be clarified. Our results indicated that JQ1 treatment suppressed cardiac fibrosis and improved cardiac function in a STZ-induced diabetic mouse model. We further used both cardiofibroblasts and cardiomyocytes in vitro to investigate the protective mechanism of JQ1. JQ1 significantly suppressed hyperglycemia-induced cardiofibroblasts proliferation and migration, myofibroblast differentiation, and collagen production. Moreover, JQ1 reduced hyperglycemia-induced apoptosis of cardiomyocytes in vitro and in vivo. Mechanistically, JQ1 treatment could reverse the expression of Caveolin-1, which modulates transforming growth factor-β1 (TGF-β1) signaling in cardiofibroblasts and inhibits cardiomyocytes apoptosis. Our findings identify BET inhibitor JQ...Continue Reading

Citations

Mar 31, 2019·The Journal of Physiology·Arun Padmanabhan, Saptarsi M Haldar
Jun 13, 2020·International Journal of Molecular Sciences·Julio M Martinez-MorenoAna B Sanz
Feb 13, 2021·Life Sciences·Xuping LiYuanyuan Cheng

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