title: Cardiac microRNA-133 is down-regulated in thyroid hormone-mediated cardiac hypertrophy partially via Type 1 Angiotensin II receptor.
abstract: Elevated thyroid hormone (TH) levels induce cardiac hypertrophy partially via type 1 Angiotensin II receptor (AT1R). MicroRNAs (miRNAs) are key regulators of cardiac homeostasis, and miR-133 has been shown to be involved in cardiac hypertrophy. However, the potential role of miR-133 in cardiac growth induced by TH is unknown. Thus, we aimed to investigate the miR-133 expression, as well as its potential role in cardiac hypertrophy in response to TH. Wistar rats were subjected to hyperthyroidism combined or not with the AT1R blocker. T3 serum levels were assessed to confirm the hyperthyroid status. TH induced cardiac hypertrophy, as evidenced by higher cardiac weight/tibia length ratio and α-actin mRNA levels, which was prevented by AT1R blocker. miR-133 expression was decreased in TH-induced cardiac hypertrophy in part through the AT1R. Additionally, the cardiac mRNA levels of miR-133 targets, SERCA2a and calcineurin were increased in hyperthyroidism partially via AT1R, as evaluated by real-time RT-PCR. Interestingly, miR-133 levels were unchanged in T3-induced cardiomyocyte hypertrophy in vitro. However, a gain-of-function study revealed that miR-133 mimic blunted the T3-induced cardiomyocyte hypertrophy in vitro. Together, our data indicate that miR-133 expression is reduced in TH-induced cardiac hypertrophy partially by the AT1R and that miR-133 mimic prevents the cardiomyocyte hypertrophy in response to T3 in vitro. These findings provide new insights regarding the mechanisms involved in the cardiac growth mediated by TH, suggesting that miR-133 plays a key role in TH-induced cardiomyocyte hypertrophy.
authors.affiliation: Laboratory of Cell Biology and Functional Anatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 2415, São Paulo, SP, 05508-900, Brazil. gpdiniz@usp.br.
authors.forename: Gabriela Placoná
authors.initials: GP
authors.lastname: Diniz
authors.affiliation: Laboratory of Cell Biology and Functional Anatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 2415, São Paulo, SP, 05508-900, Brazil.
authors.forename: Caroline Antunes
authors.initials: CA
authors.lastname: Lino
authors.affiliation: Laboratory of Cell Biology and Functional Anatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 2415, São Paulo, SP, 05508-900, Brazil.
authors.forename: Elaine Castilho
authors.initials: EC
authors.lastname: Guedes
authors.affiliation: Laboratory of Cell Biology and Functional Anatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 2415, São Paulo, SP, 05508-900, Brazil.
authors.forename: Luana do Nascimento
authors.initials: Ldo N
authors.lastname: Moreira
authors.affiliation: Laboratory of Cell Biology and Functional Anatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 2415, São Paulo, SP, 05508-900, Brazil.
authors.forename: Maria Luiza Morais
authors.initials: ML
authors.lastname: Barreto-Chaves
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006332:Cardiomegaly / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D006980:Hyperthyroidism / Q000150:complications; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D032383:Myocytes, Cardiac / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013963:Thyroid Hormones / Q000009:adverse effects
chemical_list: C549446:MIRN133 microRNA, rat; D035683:MicroRNAs; D044140:Receptor, Angiotensin, Type 1; D013963:Thyroid Hormones
keywords: Angiotensin II receptor; Calcineurin; Cardiac hypertrophy; MicroRNA-133; SERCA2a; Thyroid hormone