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Current Medicinal Chemistry
ISSN (Print): 0929-8673
ISSN (Online): 1875-533X
DOI: 10.2174/09298673113209990172      Price:  $58

The Role of Transcription Factors in the Formation of an Arrhythmogenic Substrate in Congestive Human Heart Failure

Author(s): J.S. Schulte, M.D. Seidl and F.U. Muller
Pages 1281-1298 (18)
Human congestive heart failure is accompanied by structural and electrical alterations leading to the development of an arrhythmogenic substrate. This substrate is associated with the “sudden cardiac death” due to ventricular tachycardia or ventricular fibrillation. Multiple studies link distinct transcription factors to the transcriptional regulation of genes related to the formation of an arrhythmogenic substrate. In addition to cardiac hypertrophy the up- or downregulation of ion channels, calcium-handling proteins, and proteins forming gap junctions play a pivotal role in the progression of heart failure. This review summarizes the transcriptional regulation of selected genes implicated in the formation of an arrhythmogenic substrate. In this context we provide an overview of relevant transcription factors, activating stimuli and pathways, the evidence of binding to respective elements in the promoter of target genes and the associated mRNA regulation in animal models. Finally, possible therapeutic consequences are discussed.
Arrhythmogenic substrate, cardiac remodeling, gene regulation, human heart failure, hypertrophic response, transcription factors.
Institute of Pharmacology and Toxicology, University of Munster, Domagkstr. 12, 48149 Munster, Germany.