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Semin Thromb Hemost 2010; 36(2): 185-194
DOI: 10.1055/s-0030-1251503
© Thieme Medical Publishers

The Role of HMGB1/RAGE in Inflammatory Cardiomyopathy

Hans C. Volz1 , Ziya Kaya1 , Hugo A. Katus1 , Martin Andrassy1
  • 1Department of Medicine III, University of Heidelberg, Heidelberg, Germany
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Publication History

Publication Date:
22 April 2010 (online)

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ABSTRACT

Heart failure is an increasingly prevalent disorder with considerable morbidity and mortality. Although many causal mechanisms such as inherited cardiomyopathies, ischemic cardiomyopathy, or muscular overload are easily identified in clinical practice, the events that determine the progression of cardiac injury to heart failure and adverse ventricular remodeling are still unclear. Yet there is compelling evidence that inflammatory mechanisms contribute to the progression of heart failure. High-mobility group box-1 (HMGB1) is a newly recognized potent innate “danger signal” that is released by necrotic cells and by activated immune cells. HMGB1 signals via the receptor for advanced glycation end-product (RAGE) and members of the toll-like receptor (TLR) family. We have demonstrated an important role for HMGB1 and RAGE in the pathogenesis of early- and late-phase complications following ischemia/reperfusion (I/R) injury of the heart. In addition, enhanced postmyocardial infarction remodeling in type 1 diabetes mellitus was partially mediated by HMGB1 activation. We propose that the interaction of HMGB1 and RAGE is a key component initiating and sustaining the inflammatory response in inflammatory cardiomyopathy eventually leading to heart failure. Thus HMGB1-antagonizing gene therapy represents a new therapeutic strategy.

KEYWORDS

HMGB1 - inflammation - innate immunity - inflammatory cardiomyopathy

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Martin AndrassyM.D. 

Department of Medicine III, University of Heidelberg

INF 410, 69120 Heidelberg, Germany

Email: martin.andrassy@med.uni-heidelberg.de

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