The present study, therefore, was designed to test our hypothesis: (a) Ang II treatment exacerbates diabetes-induced cardiac hypertrophy and remolding due to autophagy inhibition, independent of increased BP; (b) inhibited cardiac autophagy in diabetes and/or Ang II exposure may be mediated by increased miR-221 expression that further inhibits autophagy negative regulator p27 function; and (c) increased level of miR-221 in diabetes and/or Ang II condition may be mediated by diabetes- and/or Ang II-increased JNK/c-Jun-mediated transcription. This evidence concerns the gene JUN and cardiac hypertrophy.