Cardiac microRNAs Alterations in Pacing‐Induced Heart Failure

microRNAs (miRs) are emerging as key intracellular regulators that downregulate the translation of target messenger RNAs. We have previously identified, in a ventricular tachypacing dog model of dilated cardiomyopathy, a group of 156 genes that are up‐ or downregulated in myocardium only during the transition from compensated to decompensated heart failure (HF). Therefore we tested whether this altered profile is associated to a specific miRs pattern. miRs microarray analysis revealed that 146 miRs were differentially expressed in failing (n=3) versus normal (n=3) dog hearts: 96 were upregulated and 50 downregulated (±1.5 fold, P<0.05). Using the Refgene database, 30 messenger RNAs uniquely altered in HF resulted as the target of at least one of the differentially expressed miRs. For instance, miR‐687 and miR‐550 were reduced and miR‐570 was upregulated, consistent with the marked upregulation and downregulation of their respective target mRNAs encoding for monoamine oxidase B, matrix metalloproteinase 2 and thioredoxin‐like protein. These enzymes are involved in tissue remodeling and oxidative stress, which importantly contribute to the progression of HF. In conclusion, we have determined a novel alteration of the miRs expression profile in a large animal model of severe HF. Our data will contribute to elucidate pathogenic mechanisms causing cardiac decompensation. Supported by USPHS HL‐74237, ‐43023