MicroRNAs: novel regulators in cardiac development and disease.
MicroRNAs (miRNAs) are endogenous, small ribonucleotides regulating the translation of target messenger RNAs that have been shown to be involved in orchestrating growth, development, function, and stress responses of various organs, including the heart. Muscle miRNAs are mainly controlled by a network of myogenic transcription factors, and throughout cardiac development they fine-tune regulatory protein levels in a spatiotemporal manner. Recent profiling studies revealed that miRNA expression patterns are derailed in both human cardiac disease and animal models of cardiac hypertrophy and failure. Modulation of miRNA expression in vitro as well as in vivo has revealed an important role of miRNAs in regulating heart function, particularly cardiac growth and conductance. Here, we overview the recent findings on miRNAs in cardiac development and disease and report the latest advances in the identification and validation of miRNA targets, which are important for a comprehensive understanding of cardiac miRNA function. Finally, we focus on the development and use of miRNA antagonists (antagomirs) to target miRNAs in vivo, which may translate into novel therapeutic strategies for heart disease in the future.
Medizinische Klinik und Poliklinik I, Universitätsklinikum, Julius-Maximilians-Universität, Josef-Schneider-Street 2, D-97080 Würzburg, Germany. Thum_T@klinik.uni-wuerzburg.de
Thomas
T
Thum
Daniele
D
Catalucci
Johann
J
Bauersachs
D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000503:physiopathology; D018507:Gene Expression Regulation, Developmental; D015316:Genetic Therapy / Q000379:methods; D006321:Heart / Q000196:embryology* / Q000254:growth & development; D006331:Heart Diseases / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D006333:Heart Failure / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D024510:Muscle Development / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism*; D009841:Oligonucleotides / Q000627:therapeutic use
D035683:MicroRNAs; D009841:Oligonucleotides