Rodent heart failure models do not reflect the human circulating microRNA signature in heart failure
| Autor: | Peter van der Meer, Atze van der Pol, Ekaterina S. Ovchinnikova, Adriaan A. Voors, Laura M G Meems, Eugene Berezikov, Rudolf A. de Boer, Eline L. Vegter, A. Rogier van der Velde, Herman H W Silljé |
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| Přispěvatelé: | Cardiovascular Centre (CVC), Stem Cell Aging Leukemia and Lymphoma (SALL), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Physiology Peptide Hormones lcsh:Medicine Blood Pressure PROGRESSION 030204 cardiovascular system & hematology Biochemistry Vascular Medicine DISEASE Rats Sprague-Dawley Mice 0302 clinical medicine Atrial natriuretic peptide Medicine and Health Sciences lcsh:Science CARDIAC-HYPERTROPHY Mammals Multidisciplinary Ejection fraction Heart Animal Models Magnetic Resonance Imaging Systolic Pressure Body Fluids Nucleic acids medicine.anatomical_structure Blood Experimental Organism Systems Vertebrates Cardiology Rats Transgenic Anatomy Research Article Cardiac function curve medicine.medical_specialty BIOMARKERS Mouse Models Biology Research and Analysis Methods Rodents Blood Plasma 03 medical and health sciences Model Organisms Natriuretic Peptide Internal medicine Renin–angiotensin system medicine Genetics INJURY KINASE Animals Humans Non-coding RNA Heart Failure Lung Biology and life sciences HYPERTENSION lcsh:R Hemodynamics Organisms medicine.disease Hormones Rats Gene regulation Atrial Natriuretic Peptide Circulating MicroRNA Disease Models Animal MicroRNAs 030104 developmental biology Endocrinology Blood pressure Heart failure Amniotes RNA lcsh:Q Gene expression |
| Zdroj: | PLoS ONE, Vol 12, Iss 5, p e0177242 (2017) PLoS ONE PLoS ONE, 12(5):e0177242. PUBLIC LIBRARY SCIENCE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0177242 |
| Popis: | IntroductionWe recently identified a set of plasma microRNAs (miRNAs) that are downregulated in patients with heart failure in comparison with control subjects. To better understand their meaning and function, we sought to validate these circulating miRNAs in 3 different well-established rat and mouse heart failure models, and correlated the miRNAs to parameters of cardiac function.MethodsThe previously identified let-7i-5p, miR-16-5p, miR-18a-5p, miR-26b-5p, miR-27a-3p, miR30e-5p, miR-199a-3p, miR-223-3p, miR-423-3p, miR-423-5p and miR-652-3p were measured by means of quantitative real time polymerase chain reaction (qRT-PCR) in plasma samples of 8 homozygous TGR(mREN2)27 (Ren2) transgenic rats and 8 (control) Sprague-Dawley rats, 6 mice with angiotensin II-induced heart failure (AngII) and 6 control mice, and 8 mice with ischemic heart failure and 6 controls. Circulating miRNA levels were compared between the heart failure animals and healthy controls.ResultsRen2 rats, AngII mice and mice with ischemic heart failure showed clear signs of heart failure, exemplified by increased left ventricular and lung weights, elevated end-diastolic left ventricular pressures, increased expression of cardiac stress markers and reduced left ventricular ejection fraction. All miRNAs were detectable in plasma from rats and mice. No significant differences were observed between the circulating miRNAs in heart failure animals when compared to the healthy controls (all P>0.05) and no robust associations with cardiac function could be found.ConclusionsThe previous observation that miRNAs circulate in lower levels in human patients with heart failure could not be validated in well-established rat and mouse heart failure models. These results question the translation of data on human circulating miRNA levels to experimental models, and vice versa the validity of experimental miRNA data for human heart failure. |
| Databáze: | OpenAIRE |
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