MicroRNA profiling in early hypertrophic growth of the left ventricle in rats

Abstract

Pressure overload induces hypertrophic growth of the heart and in the long term this condition can lead to cardiomyopathy and heart failure. Several miRNAs are upregulated in heart failure. However, it is not clear, which miRNAs (if any) are induced during the early hypertrophic growth phase. To investigate whether the upregulation of miRNAs is an integrated part of hypertrophic growth or an effect of cardiac disease we investigated miRNA expression in early hypertrophic development. Hypertrophy was induced by banding of the ascending aorta of male rats. After 14 days, the heart left ventricle weight relative to body weight of animals with aortic banding had increased 65% compared to matched control rats. Furthermore, RNA was extracted from left ventricles and reverse transcription qPCR showed that expression of the hypertrophic markers atrial natriuretic peptide and brain natriuretic peptide was highly induced in animals with aortic banding. Out of 13 miRs that have previously been reported to be associated with late-stage pressure-overload-induced hypertrophy and heart failure only four (miR-23a, miR-27b, miR-125b and miR-195) were induced during early hypertrophic growth. These miRs were previously associated with angiogenesis and cell growth and their expression in early hypertrophic growth was accompanied by a twofold upregulation of the cell-cycle regulator cyclin D2 that is a marker of cardiac growth. Our results indicate that different miRNAs are involved in early hypertrophic growth than in late stage pressure-overload induced heart failure.