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Center for Molecular Cardiology

Apabetalone-mediated BET Inhibition Rescues Diabetes-induced Impairment of Angiogenic Response

Redox

Modulation of blood vessel growth holds promise for the prevention of limb ischaemia, which is particularly important and therapeutically relevant in diabetic (DM) patients with peripheral artery disease (PAD). Epigenetic changes, namely posttranslational histone modifications, participate in angiogenic response suggesting that chromatin-modifying drugs could exert beneficial effects in this setting. In this elegant study, Shafeeq Mohammed et al. nicely demonstrate that Apabetalone (APA), a selective inhibitor of bromodomain (BRD) and extra-terminal (BET) proteins, prevents the interaction of BRD4 with chromatin thus modulating transcriptional programs. Indeed, by using an array of in vitro and in vivo setups, the authors convincingly show that BET protein inhibition by APA restores angiogenic response in experimental diabetes. These findings set the stage for independent preclinical studies and eventually clinical trials testing APA in diabetic PAD. Check out the full article now available online ahead of print.

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