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Contents

Volume 36, Issue 32, 21 August 2015

ISSUE @ A GLANCE

EDITORIALS

REVIEWS

Imaging

FASTTRACK CLINICAL RESEARCH

Disease management

CLINICAL RESEARCH

Imaging

Valvular heart disease

BASIC SCIENCE

  • Johan M. Lorenzen, Celina Schauerte, Anika Hübner, Malte Kölling, Filippo Martino, Kristian Scherf, Sandor Batkai, Karina Zimmer, Ariana Foinquinos, Tamas Kaucsar, Jan Fiedler, Regalla Kumarswamy, Claudia Bang, Dorothee Hartmann, Shashi K. Gupta, Jan Kielstein, Andreas Jungmann, Hugo A. Katus, Frank Weidemann, Oliver J. Müller, Hermann Haller, Thomas Thum Eur Heart J (2015) 36 (32): 2184-2196 DOI: http://dx.doi.org/10.1093/eurheartj/ehv109 First published online: 21 April 2015 (13 pages)

    Osteopontin (OPN) is a pleiotropic cytokine, which has been shown to be a pivotal factor in myofibroblast activation in cardiac fibrosis, thereby acting as a strong driver of heart failure development in humans. MicroRNAs (miRNAs) are under intense investigation as powerful regulators of various diseases. First phase I and II clinical trials using miRNA inhibitors have been initiated. We here show, that OPN is essential in the activation of AP-1 and subsequent transcription of miR-21 in cardiac fibrosis related to Ang II. OPN null mice are protected from miR-21 increase and fibrosis development due to impaired AP-1 activation and fibroblast activation. In the future, these findings may result in miRNA therapeutic approaches to treat patients with cardiac remodelling, in which levels of OPN and miR-21 are increased.