MicroRNA‐1 overexpression blunts cardiomyocyte hypertrophy elicited by thyroid hormone

Abstract

It is well-known that increased thyroid hormone (TH) levels induce cardiomyocyte growth. MicroRNAs (miRNAs) have been identified as key players in cardiomyocyte hypertrophy, which is associated with increased risk of heart failure. In this study, we evaluated the miR-1 expression in TH-induced cardiac hypertrophy, as well as the potential involvement of miR-1 in cardiomyocyte hypertrophy elicited by TH in vitro. The possible role of type 1 angiotensin II receptor (AT1R) in the effect promoted by TH in miR-1 expression was also evaluated. Neonatal rat cardiac myocytes (NRCMs) were treated with T for 24 hr and Wistar rats were subjected to hyperthyroidism for 14 days combined or not with AT1R blocker. Real Time RT-PCR analysis indicated that miR-1 expression was decreased in cardiac hypertrophy in response to TH in vitro and in vivo, and this effect was unchanged by AT1R blocker. In addition, HDAC4, which is target of miR-1, was increased in NRCMs after T treatment. A gain-of-function study revealed that overexpression of miR-1 prevented T -induced cardiomyocyte hypertrophy and reduced HADC4 mRNA levels in NRCMs. In vivo experiments confirmed the downregulation of miR-1 in cardiac tissue from hyperthyroid animals, which was accompanied by increased HDAC4 mRNA levels. In addition, HDAC inhibitor prevented T -induced cardiomyocyte hypertrophy. Our data reveal a new mechanistic insight into cardiomyocyte growth in response to TH, suggesting that miR-1 plays a role in cardiomyocyte hypertrophy induced by TH potentially via targeting HADC4.

MicroRNAs in Cardiac Hypertrophy

“…MiR-1 can also protect the heart against hypertrophy by regulating the cyclin D kinase 6-retinoblastoma (CDK6-Rb) pathway and levels of thyroid hormone (TH) [44,45]. Hypertrophic rat cardiomyocytes transfected with miR-1 mimics or CDK6 siRNA inhibit activation of the CDK6-Rb pathway, which is an important pathway in the regulation of cell cycle progression contributing to cardiac hypertrophy [44,46].…”

“…In a recent study, Diniz et al [45] report that overexpression of miR-1 prevented TH-induced cardiac hypertrophy, as indicated by decreased levels of atrial natriuretic peptide (ANP) and alpha-myosin heavy chain (α-MHC), two markers of cardiac hypertrophy. In addition, TH was found to induce hypertrophy by targeting histone deacetylase-4 (HDAC4).…”

“…In addition, TH was found to induce hypertrophy by targeting histone deacetylase-4 (HDAC4). Indeed, overexpression of miR-1 reduced the expression of HDAC4, and inhibition of HDAC4 gene helped attenuate TH-induced cardiac hypertrophy [45].…”

Functional Screening Identifies MicroRNA Regulators of Corin Activity and Atrial Natriuretic Peptide Biogenesis

“…In fact, miR-1-3p was ranked as the single most tissue-specific miRNA in a recent study (25). Moreover, miR-1-3p is one of the most abundant miRNAs in cardiomyocytes, with reported roles in cardiac development (26) and disease (27–29). We confirmed that miR-1-3p was the predominant miR-1 family member in iPS-CM, as well as in human atrial and ventricular tissue (Fig.…”

MicroRNA-129-5p targets keap-1 to protect against cardiomyocyte hypertrophy via Nrf2 pathway

“…It is found that there are many kinds of miRNAs in the endothelial cells and smooth muscle cells of vascular walls and myocardial cells, which are involved in many cell biology processes, such as cell proliferation, migration, and differentiation, playing an important role in normal development of the heart and blood vessels [22]. Previous studies also have demonstrated that many miRNAs, such as miR-1 [23], miR-101b [24] are both down-regulated in cardiac hypertrophy, and overexpression of miR-1 and miR-101b both play an anti-hypertrophic role by suppressing hypertrophic responses. At the same time, there are also some other miRNAs, such as miR-297 [25], miR-22 [26] are upregulated in cardiac hypertrophy and the deletion of theses related miRNAs also has the effect to attenuate hypertrophic responses.…”