Endomyocardial miR-133a levels correlate with myocardial inflammation, improved left ventricular function, and clinical outcome in patients with inflammatory cardiomyopathy.
Inflammatory heart disease represents an important cause of chronic dilated cardiomyopathy (DCM). Predicting the clinical course of patients with inflammatory cardiomyopathy (iCMP) is difficult, and the prognostic value of current biological markers remains controversial. We tested whether expression of selected microRNAs in endomyocardial biopsies (EMBs) is related to LV functional recovery and clinical events in iCMP patients.



EMBs were obtained from patients with iCMP (n = 76) and non-inflammatory DCM (n = 22). A set of six microRNAs implicated in inflammation (miR-155 and miR-146b), heart failure (miR-21 and miR-133a), and endothelial cell (miR-126) and skeletal muscle function (miR-206) was pre-defined. Endomyocardial expression of miR-155 and miR-133a, as quantified by reverse transcription-PCR (RT-PCR), was up-regulated in patients with iCMP as compared with patients with DCM. Levels of miR-133a (R = 0.73, P < 0.01) and miR-155 (R = 0.63, P < 0.01) correlated with inflammatory cell count on EMBs from patients with iCMP. Patients with iCMP and preserved LV function at study entry demonstrated higher expression of miR-133a than patients with reduced LV function. Also, increased expression of miR-133a was associated with less fibrosis and myocyte necrosis on EMB, and LV functional recovery during a mean follow-up of 3.1 years. Importantly, patients with iCMP and miR-133a levels in the upper tertile showed longer survival free of death, malignant arrhythmias, and hospitalizations for heart failure.



The present study demonstrates that miR-133a levels correlate with macrophage infiltration, cardiac injury, improved LV function, and clinical outcome in patients with iCMP. miR-133a may serve as a potential novel biomarker and therapeutic target in human iCMP.
Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center, Leipzig, Germany.
Christian
C
Besler
Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center, Leipzig, Germany.
Daniel
D
Urban
Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center, Leipzig, Germany.
Stefan
S
Watzka
Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center, Leipzig, Germany.
David
D
Lang
Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center, Leipzig, Germany.
Karl-Philipp
KP
Rommel
Institute for Pathology and Neuropathology, Department of Molecular Pathology, University Hospital Tuebingen, Tuebingen, Germany.
Reinhard
R
Kandolf
Institute for Pathology and Neuropathology, Department of Molecular Pathology, University Hospital Tuebingen, Tuebingen, Germany.
Karin
K
Klingel
Medical Clinic II (Department of Cardiology, Angiology and Intensive Care Medicine), University Heart Center, University of Schleswig-Holstein, Luebeck, Germany.
Holger
H
Thiele
Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center, Leipzig, Germany.
Axel
A
Linke
Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center, Leipzig, Germany.
Gerhard
G
Schuler
Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center, Leipzig, Germany.
Volker
V
Adams
Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center, Leipzig, Germany.
Philipp
P
Lurz
D000328:Adult; D000368:Aged; D002311:Cardiomyopathy, Dilated / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007249:Inflammation; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009205:Myocarditis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000276:immunology / Q000378:metabolism*; D011379:Prognosis; D011446:Prospective Studies; D020127:Recovery of Function; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018487:Ventricular Dysfunction, Left / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D016277:Ventricular Function, Left
C527111:MIRN126 microRNA, human; C548234:MIRN133 microRNA, human; C542542:MIRN146 microRNA, human; C524942:MIRN155 microRNA, human; C546087:MIRN206 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs
Dilated cardiomyopathy; Endomyocardial biopsy ; Fibrosis; Heart failure; Inflammatory cardiomyopathy; MicroRNA; Myocarditis