Overexpression of miRNA‐195 induced by hyperthyroidism is attenuated by the AT1 receptor blockage (868.6)

Abstract

Introduction: miRNA‐195 is increased during cardiac hypertrophy, and it´s overexpression is sufficient to drive cardiac growth. We demonstrated that the AT1 receptor (AT1R) participates of the thyroid hormone (TH)‐induced cardiac hypertrophy. However, the potential modulation of the miRNA‐195 in TH‐mediated cardiac growth, as well as the possible contribution of the AT1R in this event is unknown.Objective: The aim of this study was to investigate the cardiac miRNA‐195 levels in TH‐induced cardiac hypertrophy, as well as the potential role of the AT1R in this response.Methods: The hyperthyroidism was induced by injections of T4 for 14 days. The T4 group was subdivided into two groups: T4 and T4 plus Losartan (an AT1R blocker). Cardiac hypertrophy was assessed by heart weight (HW) to tibia length (TL) ratio and by the ANF and skeletal‐alpha actin gene expression. The analysis of the miRNA levels was assessed by miRNA Stem Loop RT‐PCR. Data are presented as mean±SD (n=5).Results: The hyperthyroid group presented cardiac hypertrophy, as evaluated by the higher HW to TL length ratio, as well as by the increased ANF and skeletal‐alpha actin mRNA levels. However, the AT1R blocker prevented the cardiac hypertrophy induced by T4. In addition, the cardiac growth in response to TH was accompanied by higher cardiac levels of miRNA‐195 (4.9±0.7, P<0.01 vs control), which were attenuated by the use of the AT1R blocker (2.1±0.5, P<0.01 vs T4).Conclusions: These results evidence for the first time that T4‐induced cardiac hypertrophy is accompanied by a cardiac overexpression of miRNA‐195, and that the AT1R participates at least in part of this response.Grant Funding Source: Supported by FAPESP (Foundation for the Support of Research in the State of Sao Paulo) and by CNPq.