MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts

  title={MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts},
  author={Thomas Thum and Carina Gross and Jan Fiedler and Thomas Fischer and Stephan Kissler and Markus Bussen and Paolo Galuppo and Steffen Just and Wolfgang Rottbauer and Stefan Frantz and Mirco Castoldi and J{\"u}rgen Soutschek and Victor E. Koteliansky and Andreas Rosenwald and Michiel A. Basson and Jonathan D. Licht and John T. G. Pena and Sara H. Rouhanifard and Martina U. Muckenthaler and Thomas Tuschl and Gail Roberta Martin and Johann Bauersachs and Stefan Engelhardt},
MicroRNAs comprise a broad class of small non-coding RNAs that control expression of complementary target messenger RNAs. Dysregulation of microRNAs by several mechanisms has been described in various disease states including cardiac disease. Whereas previous studies of cardiac disease have focused on microRNAs that are primarily expressed in cardiomyocytes, the role of microRNAs expressed in other cell types of the heart is unclear. Here we show that microRNA-21 (miR-21, also known as Mirn21… 
Role of MicroRNAs in Cardiovascular Disease: Therapeutic Challenges and Potentials
Several of the miRs known to change in expression in association with heart failure are summarized and details of what is known about their putative targets are outlined.
Crucial Role of miR-433 in Regulating Cardiac Fibrosis
It is reported that miR-433 was consistently elevated in three models of heart disease with prominent cardiac fibrosis, and was enriched in fibroblasts compared to cardiomyocytes, and this work suggests that mi R-433 is a potential target for amelioration of cardiac Fibrosis.
MicroRNA-1-Mediated Inhibition of Cardiac Fibroblast Proliferation Through Targeting Cyclin D2 and CDK6
The findings demonstrate miRNA-1 expression and regulation in adult ventricular fibroblasts, where it acts as a novel negative regulator of adult cardiac fibroblast proliferation that is at least partially mediated by direct targeting of two cell cycle regulators.
MicroRNA-22 increases senescence and activates cardiac fibroblasts in the aging heart
MiR-22 upregulation in the aging heart contributed at least partly to accelerated cardiac fibroblast senescence and increased migratory activity and the results suggest an involvement of miR- 22 in age-associated cardiac changes, such as cardiac fibrosis.
MicroRNA-21 in Cardiovascular Disease
MicroRNA-21 (miR-21) is a highly expressed microRNA (miRNA) in cardiovascular system. Recent studies have revealed that its expression is deregulated in heart and vasculature under cardiovascular
MicroRNA-350 induces pathological heart hypertrophy by repressing both p38 and JNK pathways.
MicroRNA Therapeutics in Cardiovascular Disease
This chapter will describe the key data demonstrating the potential of miRNAs either to prevent cardiac hypertrophy or to improve cardiac function in heart failure as well as strategies to improve druggability parameters and delivery characteristics of selected candidates.
Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice.
It is shown here that miR-21-null mice are normal and, in response to a variety of cardiac stresses, display cardiac hypertrophy, fibrosis, upregulation of stress-responsive cardiac genes, and loss of cardiac contractility comparable to wild-type littermates.
MicroRNA-21–Dependent Macrophage-to-Fibroblast Signaling Determines the Cardiac Response to Pressure Overload
Systematic quantification of intercellular communication mediated by ligand-receptor interactions across all cell types revealed that miR-21 primarily determined macrophage-fibroblast communication, promoting the transition from quiescent fibroblasts to myofibro Blasts.
Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy.
It is found that cardiac fibroblasts secrete star miRNA-enriched exosomes and fibroblast-derived miR-21* is identified as a paracrine signaling mediator of cardiomyocyte hypertrophy that has potential as a therapeutic target.


MicroRNA-133 controls cardiac hypertrophy
The data show thatmiR-133, and possibly miR-1, are key regulators of cardiac hypertrophy, suggesting their therapeutic application in heart disease.
MicroRNAs Play an Essential Role in the Development of Cardiac Hypertrophy
It is proposed that microRNAs play an essential regulatory role in the development of cardiac hypertrophy, wherein downregulation of miR-1 is necessary for the relief of growth-related target genes from its repressive influence and induction ofhypertrophy.
The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2
It is shown that miR-1 is overexpression in individuals with coronary artery disease, and that when overexpressed in normal or infarcted rat hearts, it exacerbates arrhythmogenesis and is a potential antiarrhythmic target.
MicroRNAs in the Human Heart: A Clue to Fetal Gene Reprogramming in Heart Failure
Evidence is provided that cardiac microRNAs, recently discovered key regulators of gene expression, contribute to the transcriptional changes observed in heart failure as well as changes in gene expression comparable to the failing heart.
A microRNA component of the p53 tumour suppressor network
A family of miRNAs, miR-34a–c, whose expression reflected p53 status is described, whose encoded genes are direct transcriptional targets of p53, whose induction by DNA damage and oncogenic stress depends on p53 both in vitro and in vivo.
The transcriptional repressor Nab1 is a specific regulator of pathological cardiac hypertrophy
Transgenic mice with cardiac-specific overexpression of Nab1 showed that Nab1 is a potent inhibitor of cardiac growth in response to pathological stimuli in vivo, implicate the Nab1-Egr1 axis as a crucial regulator of pathological cardiac growth.
MicroRNAs are aberrantly expressed in hypertrophic heart: do they play a role in cardiac hypertrophy?
It is demonstrated for the first time that miRNAs are aberrantly expressed in hypertrophic mouse hearts after aortic banding and the results suggest that mi RNAs are involved in the cardiac hypertrophy formation.
MicroRNA-21 targets Sprouty2 and promotes cellular outgrowths.
It is proposed that an increase in miR-21 enhances the formation of various types of cellular protrusions through directly targeting and down-regulating SPRY2.