title: MicroRNAs are aberrantly expressed in hypertrophic heart: do they play a role in cardiac hypertrophy?
abstract: MicroRNAs (miRNAs) are a recently discovered class of endogenous, small, noncoding RNAs that regulate gene expression. Although miRNAs are highly expressed in the heart, their roles in heart diseases are currently unclear. Using microarray analysis designed to detect the majority of mammalian miRNAs identified thus far, we demonstrated that miRNAs are aberrantly expressed in hypertrophic mouse hearts. The time course of the aberrant miRNA expression was further identified in mouse hearts at 7, 14, and 21 days after aortic banding. Nineteen of the most significantly dysregulated miRNAs were further confirmed by Northern blot and/or real-time polymerase chain reaction, in which miR-21 was striking because of its more than fourfold increase when compared with the sham surgical group. Similar aberrant expression of the most up-regulated miRNA, miR-21, was also found in cultured neonatal hypertrophic cardiomyocytes stimulated by angiotensin II or phenylephrine. Modulating miR-21 expression via antisense-mediated depletion (knockdown) had a significant negative effect on cardiomyocyte hypertrophy. The results suggest that miRNAs are involved in cardiac hypertrophy formation. miRNAs might be a new therapeutic target for cardiovascular diseases involving cardiac hypertrophy such as hypertension, ischemic heart disease, valvular diseases, and endocrine disorders.
authors.affiliation: Cardiovascular Research Laboratory, Vascular Biology Center and Department of Surgery, University of Tennessee Health Science Center, 956 Court Avenue, Memphis, TN 38163, USA.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Cheng
authors.forename: Ruirui
authors.initials: R
authors.lastname: Ji
authors.forename: Junming
authors.initials: J
authors.lastname: Yue
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Liu
authors.forename: He
authors.initials: H
authors.lastname: Chen
authors.forename: David B
authors.initials: DB
authors.lastname: Dean
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D006332:Cardiomegaly / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006321:Heart / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D000804:Angiotensin II