Reciprocal Repression Between MicroRNA-133 and Calcineurin Regulates Cardiac Hypertrophy

Abstract

Abstract-Cardiac hypertrophy involves a remodeling process of the heart in response to diverse pathological stimuli. Both calcineurin/nuclear factor of activated T cells pathway and microRNA-133 (miR-133) have been shown to play a critical role in cardiac hypertrophy. It has been recognized that the expression and activity of calcineurin increases and miR-133 expression decreases in the hypertrophic heart, and inhibition of calcineurin or increase of miR-133 expression protects against cardiac hypertrophy. miR-133, miR-195, miR-1, miR-208, miR-21, and so forth. 2-6 Carè et al 2 reported that the expression of microRNA-133 (miR-133) decreased in mouse and human models of cardiac hypertrophy. Overexpression of miR-133 in vitro inhibited cardiac hypertrophy. In contrast, suppression of miR-133 by "decoy" sequences induced hypertrophy. Therefore, changes of miR-133 were considered as the requisites for determining cardiac hypertrophy. Calcineurin is a calcium/calmodulin-activated serinethreonine phosphatase that dephosphorylates the transcription factor, nuclear factor of activated T cells (NFAT), which translocates into the nucleus to bind to DNA and activate hypertrophic response genes. Cardiac-specific activation of calcineurin or its downstream effector NFAT is sufficient to induce cardiac hypertrophy, 7,8 and calcineurin protein levels and phosphatase activities increase in hypertrophic hearts. 9,10 In light of the antithetical functions of calcineurin and miR-133, we hypothesized that calcineurin is the target of miR-133, and the expression of miR-133 is regulated by the calcineurin/NFAT signaling pathway.

The regulatory role of microRNAs in angiogenesis‐related diseases

“…Mechanically, down‐regulated miR‐30a can aggravate pressure overload‐induced cardiomyocyte hypertrophy by activating autophagy via inhibiting beclin‐1 and loss of miR‐29 can improve hypertensive cardiac remodelling by deletion of Smad7 180. Furthermore, miR‐133 plays a key role in VSMC phenotypic conversion in vitro and in vivo via repressing Sp‐1 and patients with a lower miR‐133 level appear to be more likely to develop or progress to atherosclerosis and cardiac hypertrophy 180, 182. However, further studies are required to better understand the exact function of other miRNAs in regulating the pathogenesis of hypertension.…”

Bone Morphogenetic Protein-4 Mediates Cardiac Hypertrophy, Apoptosis, and Fibrosis in Experimentally Pathological Cardiac Hypertrophy

“…Cardiomyocytes were prepared for immunocytochemistry as described previously. 7 Detailed information is described in the online-only Data Supplement.…”

MicroRNA-133a inhibits cell proliferation, colony formation ability, migration and invasion by targeting matrix metallopeptidase 9 in hepatocellular carcinoma

“…Overall, these results indicated that MMP-9 may be a direct target of miR-133a in vitro. Discussion miR-133 is an miRNA family containing miR-133a and miR-133b; which differ by only one base in the terminal 3' position (33). miR-133a is a multicopy gene, with two copies in chromosomes 18 and 20, which are located next to another muscle-enriched miRNA, miR-1, while miR-133b is located in chromosome 6 (34).…”