Oral geranylgeranylacetone treatment increases heat shock protein expression in human atrial tissue

Denise M. S. van Marion, Larissa Dorsch, Femke Hoogstra-Berends, Tea Kakuchaya, Leo Bockeria, Natasja M. S. de Groot, Bianca J. J. M. Brundel*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

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    BACKGROUND Heat shock proteins (HSPs) are important chaperones that regulate the maintenance of healthy protein quality control in the cell. Impairment of HSPs is associated with aging-related neurodegenerative and cardiac diseases. Geranylgeranylacetone (GGA) is a compound well known to increase HSPs through activation of heat shock factor-1 (HSF1). GGA increases HSPs in various tissues, but whether GGA can increase HSP expression in human heart tissue is unknown.

    OBJECTIVE The purpose of this study was to test whether oral GGA treatment increases HSP expression in the atrial appendages of patients undergoing cardiac surgery.

    METHODS HSPB1, HSPA1, HSPD1, HSPA5, HSF1, and phosphorylated HSF1 levels were measured by western blot analysis in right and left atrial appendages (RAAs and LAAs, respectively) collected from patients undergoing coronary artery bypass grafting (CABG) who were treated with placebo (n = 13) or GGA 400 mg/da(n = 13) 3 days before surgery. Myofilament fractions were isolated from LAAs to determine the levels of HSPB1 and HSPA1 present in these fractions.

    RESULTS GGA treatment significantly increased HSPB1 and HSPA1 expression levels in RAA and LAA compared to the placebo group, whereas HSF1, phosphorylated HSF1, HSPD1, and HSPA5 were unchanged. In addition, GGA treatment significantly enhanced HSPB1 levels at the myofilaments compared to placebo.

    CONCLUSION Three days of GGA treatment is associated with higher HSPB1 and HSPA1 expression levels in RAA and LAA of patients undergoing CABG surgery and higher HSPB1 levels at the myofilaments. These findings pave the way to study the role of GGA as a protective compound against other cardiac diseases, including postoperative atrial fibrillation.

    Original languageEnglish
    Pages (from-to)115-122
    Number of pages8
    JournalHeart Rhythm
    Issue number1
    Publication statusPublished - Jan-2020


    • Atrial appendage
    • Coronary artery bypass grafting
    • Geranylgeranylacetone
    • Heat shock protein
    • Proteostasis

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