Altered biogenesis of microRNA-1 is associated with cardiac dysfunction in aging of spontaneously hypertensive rats.

Currently we face the issues of aging-associated pathologies, particularly those leading to heart failure. With that in mind, in current research we focus on aging and hypertension combination as a widely spread threating problem. In a row with functional and morphological characterization of these aging- and hypertension-associated cardiac changes, we evaluate biogenesis of microRNA-1 being one of major microRNAs in the heart. The aim of this study was to check the hypothesis if dysregulation of microRNA-1 biogenesis is associated with heart failure in aged and especially aged hypertensive rats. The experiments were carried out on male SHR and Wistar rats of age 6 months (young) and 18 months (old). The evaluation of hemodynamic parameters was performed in heart left ventricles of narcotized rats using the ultra-small 2F catheter. The development of fibrosis was determined using light and electron microscopy. Levels of mature and immature forms of microRNA-1 and mRNA encoding the proteins involved in its biogenesis were determined using reverse transcription and quantitative PCR. Aging of both Wistar and SHRs is accompanied with altered hemodynamic parameters compared with correspondent younger mates. SHRs, especially old ones, demonstrated significant heart fibrosis. In aged animals, the level of primary microRNA-1 in Wistar rats were 7 times higher (p < 0.05) and in SHR 17 times higher (p < 0.05) in comparison with young rats of the same strain. We also observed 22 times higher level of immature microRNA-1 in the heart of Wistar and 5.9 times higher level for aged hypertensive rats (p < 0.05) compared to young rats. At the same time, the level of mature microRNA-1 occurred 2.5 and 3.2 times lower in respective groups (p < 0.05). In the current study, we observe the significant dysregulation of microRNA-1 processing in the heart associated with aging and arterial hypertension.