Heat shock protein-inducing compounds as therapeutics to restore proteostasis in atrial fibrillation

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

Research output: Contribution to journalArticleAcademicpeer-review

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 cardiomyocytes. 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 cardiomyocytes 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. © 2012 Elsevier Inc.
Original languageEnglish
Pages (from-to)62-68
JournalTrends in cardiovascular medicine
Volume22
Issue number3
DOIs
Publication statusPublished - Apr 2012

Fingerprint

Heat-Shock Proteins
Atrial Fibrillation
Therapeutics
geranylgeranylacetone
Primary Prevention
Secondary Prevention
Cardiac Myocytes
Atrial Remodeling
Recurrence
Drosophila melanogaster
Tachycardia
Pharmaceutical Preparations
Cardiac Arrhythmias
Animal Models
Morbidity
Drug Therapy
Mortality

Keywords

  • atrial fibrillation
  • heat-shock proteins
  • myocytes, cardiac
  • proteostasis deficiencies

Cite this

Hoogstra-Berends, F., Meijering, R. A. M., Zhang, D., Heeres, A., Loen, L., Seerden, J-P., ... Brundel, B. J. J. M. (2012). Heat shock protein-inducing compounds as therapeutics to restore proteostasis in atrial fibrillation. Trends in cardiovascular medicine, 22(3), 62-68. https://doi.org/10.1016/j.tcm.2012.06.013
Hoogstra-Berends, Femke ; Meijering, Roelien A M ; Zhang, Deli ; Heeres, André ; Loen, Lizette ; Seerden, Jean-Paul ; Kuipers, Irma ; Kampinga, Harm H ; Henning, Robert H ; Brundel, Bianca J J M. / Heat shock protein-inducing compounds as therapeutics to restore proteostasis in atrial fibrillation. In: Trends in cardiovascular medicine. 2012 ; Vol. 22, No. 3. pp. 62-68.
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Hoogstra-Berends, F, Meijering, RAM, Zhang, D, Heeres, A, Loen, L, Seerden, J-P, Kuipers, I, Kampinga, HH, Henning, RH & Brundel, BJJM 2012, 'Heat shock protein-inducing compounds as therapeutics to restore proteostasis in atrial fibrillation', Trends in cardiovascular medicine, vol. 22, no. 3, pp. 62-68. https://doi.org/10.1016/j.tcm.2012.06.013

Heat shock protein-inducing compounds as therapeutics to restore proteostasis in atrial fibrillation. / Hoogstra-Berends, Femke; Meijering, Roelien A M; Zhang, Deli; Heeres, André; Loen, Lizette; Seerden, Jean-Paul; Kuipers, Irma; Kampinga, Harm H; Henning, Robert H; Brundel, Bianca J J M.

In: Trends in cardiovascular medicine, Vol. 22, No. 3, 04.2012, p. 62-68.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Hoogstra-Berends, Femke

AU - Meijering, Roelien A M

AU - Zhang, Deli

AU - Heeres, André

AU - Loen, Lizette

AU - Seerden, Jean-Paul

AU - Kuipers, Irma

AU - Kampinga, Harm H

AU - Henning, Robert H

AU - Brundel, Bianca J J M

N1 - Copyright © 2012 Elsevier Inc. All rights reserved.

PY - 2012/4

Y1 - 2012/4

N2 - 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 cardiomyocytes. 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 cardiomyocytes 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. © 2012 Elsevier Inc.

AB - 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 cardiomyocytes. 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 cardiomyocytes 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. © 2012 Elsevier Inc.

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