Rodent heart failure models do not reflect the human circulating microRNA signature in heart failureReport as inadecuate

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We 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.


The previously identified let-7i-5p, miR-16-5p, miR-18a-5p, miR-26b-5p, miR-27a-3p, miR-30e-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 TGRmREN227 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.


Ren2 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.


The 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.

Author: Eline L. Vegter, Ekaterina S. Ovchinnikova, Herman H. W. Silljé, Laura M. G. Meems, Atze van der Pol, A. Rogier van der Velde, E



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