Numerous clinical studies have shown that patients suffering from cardiovascular disorders such as cardiac hypertrophy have a highly specific miR expression profile. Several of these have been characterized and potential roles suggested in the development of hypertrophy. Our previous work has documented an up-regulation of both miR-199a-3p and -5p in heart and vessels of TAC and angiotensin II treated mice; as well as a downregulation following chronic moderate exercise.

Currently, we are investigating the actors implicated is this dynamic regulation. Among the signaling pathways regulating cardiac hypertrophy, we focus on microRNAs and AMPK.

Heart from C57BL/6J AMPKα1 KO or WT mice were processed for miR profiling using Maxwell miR extraction and RT-qPCR. Neonatal rat cardiomyocytes were treated with pro-hypertrophic stimuli or transfected with siRNA targeting QKI or Gld2, partners of Argonaute (Ago2). After 5days in culture, cells were harvested for miR profiling as before. An immunoprecipitation was also performed on those cells.

Our results show that, in both mice and cultured cardiomyocytes, miR-199a-5p's expression is regulated by AMPKα1. By measuring the expression of pre-miR, we highlighted that this regulation is carried via stabilization. In parallel, PKA is also implicated. Finally, our results show that a downregulation of Gld2 and QKI-7 induce a downregulation of miR-199a.

Taken together, our results suggested a role of AMPK in miR-199a-5p stabilization. Our current working hypothesis is that AMPK or PKA activates by phosphorylation Gld2. This enzyme adds a single adenine to miRNAs, the latter appears to stabilize.