Accordingly, we hypothesized that high glucose enhances activity of the transcriptional co-activator p300, leading to activation of TGF-β via acetylation of Smad2, and that by inhibiting p300, TGF-β activity will be reduced and heart failure prevented in a clinically relevant animal model of diabetic cardiomyopathy. This evidence concerns the gene EP300 and diabetic cardiomyopathy.