Common microRNA signatures in cardiac hypertrophic and atrophic remodeling induced by changes in hemodynamic load.

<h4>Background</h4>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...

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Autores principales: Ali El-Armouche, Alexander Peter Schwoerer, Christiane Neuber, Julius Emons, Daniel Biermann, Thomas Christalla, Adam Grundhoff, Thomas Eschenhagen, Wolfram Hubertus Zimmermann, Heimo Ehmke
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Publicado: Public Library of Science (PLoS) 2010
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spelling oai:doaj.org-article:f7b34f21c2c045f49d98f65bbcbf77722021-11-18T07:01:52ZCommon microRNA signatures in cardiac hypertrophic and atrophic remodeling induced by changes in hemodynamic load.1932-620310.1371/journal.pone.0014263https://doaj.org/article/f7b34f21c2c045f49d98f65bbcbf77722010-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21151612/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions</h4>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.Ali El-ArmoucheAlexander Peter SchwoererChristiane NeuberJulius EmonsDaniel BiermannThomas ChristallaAdam GrundhoffThomas EschenhagenWolfram Hubertus ZimmermannHeimo EhmkePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 12, p e14263 (2010)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ali El-Armouche
Alexander Peter Schwoerer
Christiane Neuber
Julius Emons
Daniel Biermann
Thomas Christalla
Adam Grundhoff
Thomas Eschenhagen
Wolfram Hubertus Zimmermann
Heimo Ehmke
Common microRNA signatures in cardiac hypertrophic and atrophic remodeling induced by changes in hemodynamic load.
description <h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions</h4>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.
format article
author Ali El-Armouche
Alexander Peter Schwoerer
Christiane Neuber
Julius Emons
Daniel Biermann
Thomas Christalla
Adam Grundhoff
Thomas Eschenhagen
Wolfram Hubertus Zimmermann
Heimo Ehmke
author_facet Ali El-Armouche
Alexander Peter Schwoerer
Christiane Neuber
Julius Emons
Daniel Biermann
Thomas Christalla
Adam Grundhoff
Thomas Eschenhagen
Wolfram Hubertus Zimmermann
Heimo Ehmke
author_sort Ali El-Armouche
title Common microRNA signatures in cardiac hypertrophic and atrophic remodeling induced by changes in hemodynamic load.
title_short Common microRNA signatures in cardiac hypertrophic and atrophic remodeling induced by changes in hemodynamic load.
title_full Common microRNA signatures in cardiac hypertrophic and atrophic remodeling induced by changes in hemodynamic load.
title_fullStr Common microRNA signatures in cardiac hypertrophic and atrophic remodeling induced by changes in hemodynamic load.
title_full_unstemmed Common microRNA signatures in cardiac hypertrophic and atrophic remodeling induced by changes in hemodynamic load.
title_sort common microrna signatures in cardiac hypertrophic and atrophic remodeling induced by changes in hemodynamic load.
publisher Public Library of Science (PLoS)
publishDate 2010
url https://doaj.org/article/f7b34f21c2c045f49d98f65bbcbf7772
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