The Role of Transcription Factors in the Formation of an Arrhythmogenic Substrate in Congestive Human Heart Failure
J.S. Schulte, M.D. Seidl and F.U. Muller
Affiliation: Institute of Pharmacology and Toxicology, University of Munster, Domagkstr. 12, 48149 Munster, Germany.
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.
Keywords: Arrhythmogenic substrate, cardiac remodeling, gene regulation, human heart failure, hypertrophic response, transcription
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