common microrna signatures in cardiac hypertrophic and atrophic remodeling induced by changes in hemodynamic load常见的微rna签名心脏肥厚性和萎缩性改造引起的血流动力学负荷的变化.pdfVIP

Common MicroRNA Signatures in Cardiac Hypertrophic and Atrophic Remodeling Induced by Changes in Hemodynamic Load 1,2 . 3 . 2 1 Ali El-Armouche * , Alexander Peter Schwoerer * , Christiane Neuber , Julius Emmons , Daniel 2 4 4 2 Biermann , Thomas Christalla , Adam Grundhoff , Thomas Eschenhagen , Wolfram Hubertus Zimmermann1,2, Heimo Ehmke3 1 Department of Pharmacology, University Medical Center Goettingen (UMG), Goettingen, Germany, 2 Department of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, 3 Department of Vegetative Physiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, 4 Heinrich-Pette-Institute for Experimental Virology and Immunology, Hamburg, Germany 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. Methodology/Principal Findings: 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 2663% higher in AS (n = 7) and 3362% lower in HTX (n = 7) as compared to sham-operated (n = 6) and h