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

Research output: Contribution to journalArticle

17 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

Fingerprint

geranylgeranylacetone
Heat-Shock Proteins
Atrial Fibrillation
Heart Atria
Heart Failure
Action Potentials
Ion Channels
Atrial Remodeling
Rabbits
Messenger RNA
Calcium-Transporting ATPases
Electrophysiology
Sarcoplasmic Reticulum

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Heat shock protein inducer modifies arrhythmogenic substrate and inhibits atrial fibrillation in the failing heart. / Chang, Shih Lin; Chen, Yao Chang; Hsu, Chiao Po; Kao, Yu Hsun; Lin, Yung Kuo; Lai, Yu Jun; Yeh, Hung I.; Higa, Satoshi; Chen, Shih Ann; Chen, Yi Jen.

In: International Journal of Cardiology, Vol. 168, No. 4, 09.10.2013, p. 4019-4026.

Research output: Contribution to journalArticle

Chang, Shih Lin ; Chen, Yao Chang ; Hsu, Chiao Po ; Kao, Yu Hsun ; Lin, Yung Kuo ; Lai, Yu Jun ; Yeh, Hung I. ; Higa, Satoshi ; Chen, Shih Ann ; Chen, Yi Jen. / Heat shock protein inducer modifies arrhythmogenic substrate and inhibits atrial fibrillation in the failing heart. In: International Journal of Cardiology. 2013 ; Vol. 168, No. 4. pp. 4019-4026.
@article{fcf79dea1fc44dffb810c4bd455afa8a,
title = "Heat shock protein inducer modifies arrhythmogenic substrate and inhibits atrial fibrillation in the failing heart",
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.",
keywords = "Atrial fibrillation, GGA, Heart failure, Heat shock protein, Monophasic action potential",
author = "Chang, {Shih Lin} and Chen, {Yao Chang} and Hsu, {Chiao Po} and Kao, {Yu Hsun} and Lin, {Yung Kuo} and Lai, {Yu Jun} and Yeh, {Hung I.} and Satoshi Higa and Chen, {Shih Ann} and Chen, {Yi Jen}",
year = "2013",
month = "10",
day = "9",
doi = "10.1016/j.ijcard.2013.06.072",
language = "English",
volume = "168",
pages = "4019--4026",
journal = "International Journal of Cardiology",
issn = "0167-5273",
publisher = "Elsevier Ireland Ltd",
number = "4",

}

TY - JOUR

T1 - Heat shock protein inducer modifies arrhythmogenic substrate and inhibits atrial fibrillation in the failing heart

AU - Chang, Shih Lin

AU - Chen, Yao Chang

AU - Hsu, Chiao Po

AU - Kao, Yu Hsun

AU - Lin, Yung Kuo

AU - Lai, Yu Jun

AU - Yeh, Hung I.

AU - Higa, Satoshi

AU - Chen, Shih Ann

AU - Chen, Yi Jen

PY - 2013/10/9

Y1 - 2013/10/9

N2 - 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.

AB - 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.

KW - Atrial fibrillation

KW - GGA

KW - Heart failure

KW - Heat shock protein

KW - Monophasic action potential

UR - http://www.scopus.com/inward/record.url?scp=84886262508&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84886262508&partnerID=8YFLogxK

U2 - 10.1016/j.ijcard.2013.06.072

DO - 10.1016/j.ijcard.2013.06.072

M3 - Article

C2 - 23871620

AN - SCOPUS:84886262508

VL - 168

SP - 4019

EP - 4026

JO - International Journal of Cardiology

JF - International Journal of Cardiology

SN - 0167-5273

IS - 4

ER -