Heat Shock Protein-Inducing Compounds as Therapeutics to Restore Proteostasis in Atrial Fibrillation

Femke Hoogstra-Berends, Roelien A. M. Meijering, Deli Zhang, Andre Heeres, Lizette Loen, Jean-Paul Seerden, Irma Kuipers, Harm H. Kampinga, Robert H. Henning, Bianca J. J. M. Brundel*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

25 Citations (Scopus)

Abstract

Atrial fibrillation (AF) is the most common clinical tachyarrhythmia associated with significant morbidity and mortality and is expected to affect approximately 30 million North Americans and Europeans by 2050. AF is a persistent disease, caused by progressive, often age-related, derailment of proteostasis resulting in structural remodeling of the atrial cardiornyocytes. It has been widely acknowledged that the progressive nature of the disease hampers the effective functional conversion to sinus rhythm in patients and explains the limited effect of current drug therapies. Therefore, research is directed at preventing new-onset AF by limiting the development of substrates underlying AF promotion. Upstream therapy refers to the use of drugs that modify the atrial substrate- or target-specific mechanisms of AF, with the ultimate aim to prevent the occurrence (primary prevention) and recurrence of the arrhythmia following (spontaneous) conversion and to prevent the progression of AF (secondary prevention). Recently, we observed that heat shock protein (HSP) inducing drugs, such as geranylgeranylacetone, prevent derailment of proteostasis and remodeling of cardiornyocytes and thereby attenuate the AF substrate in cellular, Drosophila melanogaster, and animal experimental models. Also, correlative data from human studies were consistent with a protective role of HSPs in preventing the progression from paroxysmal AF to permanent AF and in the recurrence of AF. In this review, we discuss novel HSP-inducing compounds as emerging therapeutics for the primary and secondary prevention of AF. (Trends Cardiovasc Med 2012;22:62-68) (c) 2012 Elsevier Inc. All rights reserved.

Original languageEnglish
Article numberPII S1050-1738(12)00206-X
Pages (from-to)62-68
Number of pages7
JournalTRENDS IN CARDIOVASCULAR MEDICINE
Volume22
Issue number3
DOIs
Publication statusPublished - Apr-2012

Keywords

  • CONTRACTILE DYSFUNCTION
  • MOLECULAR TARGETS
  • INTERVENTION
  • INDUCTION
  • DISEASES
  • MEMBERS
  • STRESS
  • HSPB

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