Clock genes in the heart - Characterization and attenuation with hypertrophy

We investigated whether the heart, like other mammalian organs, possesses i nternal clocks, and, if so, whether pressure overload-induced hypertrophy a lters the clock mechanism. Clock genes are intrinsically maintained, as sho wn by rhythmic changes even in single cells. Clocks are believed to confer a selective advantage by priming the cell for the expected environmental st imulus. In this way, clocks allow anticipation, thereby synchronizing respo nsiveness of the cell with the timing of the stimulus. We have found that i n rat heart all mammalian homologues of known Drosophila clock genes (bmal1 , clock, cry1, cry2, per1, per2, per3, dbp, hlf, and tef) show circadian pa tterns of expression and that the induction of clock output genes (the PAR [rich in proline and acidic amino acid residues] transcription factors dbp, hlf, and tef) is attenuated in the pressure-overloaded hypertrophied heart . The results expose a new dynamic regulatory system in the heart, which is partially lost with hypertrophy. Although the target genes of these PAR tr anscription factors are not known in the heart, the results provide evidenc e for a diminished ability of the hypertrophied heart to anticipate and sub sequently adapt to physiological alterations during the day.