miR-17-92 CLUSTER IS INVOLVED IN THE ANGIOGENIC SWITCH IN CARDIAC HYPERTROPHY

OBJECTIVES. MicroRNAs (miRNAs) are 21-23 nucleotide RNA molecules that regulate the stability or translational efficiency of target messenger RNAs1. miRNAs have diverse functions, including regulation of cellular differentiation, proliferation and apoptosis2, all important processes in cardiac hypertrophy. Recent studies have identified a role for several miRs in cardiac hypertrophy3-5. However, little is known about the global expression or functional roles of miRNAs in cardiac hypertrophy. We have previously shown that p300 is upregulated during hypertrophic growth of the heart, and that p300 over-expression is necessary and sufficient to induce cardiac myocyte hypertrophy in vivo, together with a marked increase in the density and size of cardiac blood vessels6. We hypothesized that p300-regulated miRNAs could participate in angiogenesis during cardiac hypertrophy. METHODS. Using Affymetrix microarrays and high-throughput real-time PCR, we carried out global expression profiling of both mRNAs and miRNAs in wild type and p300-induced hypertrophic hearts at 1 and 8 months. We measure