Heat shock protein inducer modifies arrhythmogenic substrate and inhibits atrial fibrillation in the failing heart

Shih Lin Chang, Yao Chang Chen, Chiao Po Hsu, Yu Hsun Kao, Yung Kuo Lin, Yu Jun Lai, Hung I. Yeh, Satoshi Higa, Shih Ann Chen, Yi Jen Chen

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18 Citations (Scopus)

Abstract

Background Geranylgeranylacetone (GGA) has been reported up-regulating heat shock protein (HSP) expression, and protecting against atrial remodeling. This study aimed to investigate the effects of GGA on atrial electrophysiology and inducibility of atrial fibrillation (AF) in heart failure (HF) model. Methods and results HF rabbits were created 4 weeks after coronary artery ligation. Monophasic action potential recordings and multielectrode array were used to record the electrophysiological characteristics of left atrium (LA) in normal, or HF rabbits with (HF-GGA) and without (HF-control) oral administration of GGA (200 mg/kg, 24 h before experiments). The mRNA and protein expressions of ionic channels were measured by Western blot and PCR. HF-GGA LA (n = 10), similar to normal LA (n = 10) had a shorter action potential duration (APD) and effective refractory period than HF-control LA (n = 10). HF-GGA LA had less triggered activity and APD alternans (20% vs. 100%, P = 0.001), lower maxima slope of restitution curve of APD (0.94 ± 0.04 vs.1.69 ± 0.04, P <0.001), and less inducibility of AF (50% vs. 100%, P = 0.033) than HF-control LA. HF-GGA LA had a shorter activation time and higher conduction velocity than HF-control LA. HF-GGA LA had a higher mRNA expression of Cav1.2, Nav1.5, Kir2.1, Kv1.4, Kv7.1, Kv11.1, sarcoplasmic reticulum Ca2 +-ATPase, and higher phosphorylation of phospholamban than HF-control LA. Conclusions GGA decreases triggered activity, dispersion of APD and inducibility of AF in failing heart through induction of HSP, and modulation of ionic channels and calcium homeostasis.

Original languageEnglish
Pages (from-to)4019-4026
Number of pages8
JournalInternational Journal of Cardiology
Volume168
Issue number4
DOIs
Publication statusPublished - Oct 9 2013

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Keywords

  • Atrial fibrillation
  • GGA
  • Heart failure
  • Heat shock protein
  • Monophasic action potential

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

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