title: Common microRNA signatures in cardiac hypertrophic and atrophic remodeling induced by changes in hemodynamic load.
abstract: BACKGROUND
  Mechanical overload leads to cardiac hypertrophy and mechanical unloading to cardiac atrophy. Both conditions produce similar transcriptional changes including a re-expression of fetal genes, despite obvious differences in phenotype. MicroRNAs (miRNAs) are discussed as superordinate regulators of global gene networks acting mainly at the translational level. Here, we hypothesized that defined sets of miRNAs may determine the direction of cardiomyocyte plasticity responses.
  
  
  RESULTS
  We employed ascending aortic stenosis (AS) and heterotopic heart transplantation (HTX) in syngenic Lewis rats to induce mechanical overloading and unloading, respectively. Heart weight was 26±3% higher in AS (n = 7) and 33±2% lower in HTX (n = 7) as compared to sham-operated (n = 6) and healthy controls (n = 7). Small RNAs were enriched from the left ventricles and subjected to quantitative stem-loop specific RT-PCR targeting a panel of 351 miRNAs. In total, 153 miRNAs could be unambiguously detected. Out of 72 miRNAs previously implicated in the cardiovascular system, 40 miRNAs were regulated in AS and/or HTX. Overall, HTX displayed a slightly broader activation pattern for moderately regulated miRNAs. Surprisingly, however, the regulation of individual miRNA expression was strikingly similar in direction and amplitude in AS and HTX with no miRNA being regulated in opposite direction. In contrast, fetal hearts from Lewis rats at embryonic day 18 exhibited an entirely different miRNA expression pattern.
  
  
  CONCLUSIONS
  Taken together, our findings demonstrate that opposite changes in cardiac workload induce a common miRNA expression pattern which is markedly different from the fetal miRNA expression pattern. The direction of postnatal adaptive cardiac growth does, therefore, not appear to be determined at the level of single miRNAs or a specific set of miRNAs. Moreover, miRNAs themselves are not reprogrammed to a fetal program in response to changes in hemodynamic load.
authors.affiliation: Department of Pharmacology, University Medical Center Goettingen, Goettingen, Germany. ali.el-armouche@med.uni-goettingen.de
authors.forename: Ali
authors.initials: A
authors.lastname: El-Armouche
authors.forename: Alexander Peter
authors.initials: AP
authors.lastname: Schwoerer
authors.forename: Christiane
authors.initials: C
authors.lastname: Neuber
authors.forename: Julius
authors.initials: J
authors.lastname: Emons
authors.forename: Julius
authors.initials: J
authors.lastname: Emmons
authors.forename: Daniel
authors.initials: D
authors.lastname: Biermann
authors.forename: Thomas
authors.initials: T
authors.lastname: Christalla
authors.forename: Adam
authors.initials: A
authors.lastname: Grundhoff
authors.forename: Thomas
authors.initials: T
authors.lastname: Eschenhagen
authors.forename: Wolfram Hubertus
authors.initials: WH
authors.lastname: Zimmermann
authors.forename: Heimo
authors.initials: H
authors.lastname: Ehmke
mesh_terms: D000818:Animals; D001024:Aortic Valve Stenosis / Q000473:pathology; D001284:Atrophy / Q000378:metabolism*; D006332:Cardiomegaly / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006439:Hemodynamics; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology; D010641:Phenotype; D014176:Protein Biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D035683:MicroRNAs