Pioglitazone Attenuates Inflammatory Atrial Fibrosis and Vulnerability to Atrial Fibrillation Induced by Pressure Overload in Rats

Kume, Osamu; Takahashi, Naohiko; Wakisaka, Osamu; Nagano-Torigoe, Yasuko; Teshima, Yasushi; Nakagawa, Mikiko; Yufu, Kunio; Hara, Masahide; Saikawa, Tetsunori; Yoshimatsu, Hironobu

doi:10.4020/jhrs.27.jaac_1

Cited by 20 publications

(32 citation statements)

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“…Further studies on atrial electrophysiological function may own special value to assess the impact of novel therapeutic drugs of anti-remodeling effects, such as pioglitazone (34,35) or candesartan (36), on prevention and treatment of AF.…”

Section: Discussionmentioning

confidence: 99%

Hyperglycemia aggravates atrial interstitial fibrosis, ionic remodeling and vulnerability to atrial fibrillation in diabetic rabbits

Liu

Fu²,

Li³

et al. 2012

Anadolu Kardiyol Derg

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Objective: The purpose of this study was to investigate the effects of hyperglycemia on atrial interstitial fibrosis, ionic remodeling and vulnerability to atrial fibrillation (AF) in alloxan-induced diabetic rabbits. Methods: Sixty Japanese rabbits were randomly assigned to alloxan-induced diabetic group (n=30) and control group (n=30). Ten rabbits in each group were respectively used to electrophysiological and histological study, patch-clamp study and Western blotting analysis. Langendorff perfusion was used to record inter-atrial conduction time (IACT), atrial effective refractory period (AERP) and dispersion (AERPD) and vulnerability to AF. Histological study was measured by Sirius-red stain. Patch-clamp technique was used to measure action potential duration (APD) and atrial ionic currents (INa and ICaL). Western blotting was applied to assess atrial protein expression of transforming growth factor beta 1 (TGFβ1). Results: Compared with control group, electrophysiological studies showed IACT was prolonged (37.91±6.81 vs. 27.43±1.63ms, p<0.01), AERPD was increased (30.37±8.33 vs. 14.70±5.16ms, p<0.01) in diabetic group. Inducibility of AF in diabetic group was significantly higher than in controls (8/10 vs. 1/10 of animals, p<0.01). Collagen volume fraction was increased (6.20±0.64% vs. 2.15±0.21%, p<0.01) in diabetic group. Patch-clamp studies demonstrated APD90 and APD50 were prolonged in diabetic rabbits (p<0.05 vs. control). The densities of INa were reduced and the densities of ICaL were increased (p<0.01 vs. control). Protein expression of TGFβ1 was increased in diabetic group (p<0.001 vs. control). Conclusion: Our study suggests that hyperglycemia contributes to atrial interstitial fibrosis, ionic remodeling and vulnerability to AF in diabetic rabbits, resulting in atrial structural remodeling and electrical remodeling for the development and perpetuation of AF. (Anadolu Kardiyol Derg 2012; 12: 543-50)

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Section: Discussionmentioning

confidence: 99%

Hyperglycemia aggravates atrial interstitial fibrosis, ionic remodeling and vulnerability to atrial fibrillation in diabetic rabbits

Liu

Fu²,

Li³

et al. 2012

Anadolu Kardiyol Derg

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show abstract

“…Therefore, the authors proposed that pioglitazone may inhibit AF by modulating inflammatory, oxidative stress, and hypertrophic signaling pathways involved in atrial remodeling [29]. Very recently, Kume et al showed that pioglitazone reduced inflammatory atrial fibrosis and vulnerability to AF in a pressure overload rat model of AF, possibly via the suppression of MCP-1-mediated inflammatory profibrotic processes [30]. In an in vivo rat model, Xu et al [31] reported pioglitazone inhibited age-related atrial structural remodeling and AF susceptibility via its antioxidant and anti-apoptotic effects.…”

Section: Thiazolidinedionesmentioning

confidence: 99%

Antioxidant Therapies in the Prevention and Treatment of Atrial Fibrillation

Liu¹,

Korantzopoulos²,

Li³

2013

Atrial Fibrillation - Mechanisms and Treatment

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“…The observations also suggest that pioglitazone is effective at attenuating atrial fibrosis, possibly via suppression of MCP-1-mediated inflammatory profibrotic processes. 12 To our knowledge, there have been 2 reports demonstrating the anti-AF effects of pioglitazone. Shimano et al reported that in the rapid ventricular pacing-induced congestive heart failure (CHF) of rabbits, pioglitazone reduced the duration of induced AF, attenuated atrial fibrosis, and reduced the interatrial conduction time.…”

Section: Pressure Overload and Pioglitazonementioning

confidence: 99%

“…10 In this review, we introduce our experimental approaches to the prevention of atrial fibrosis and AF. We have induced atrial fibrosis by pressure overload, 12 continuous infusion of angiotensin II (AII), 13 and 5/6 nephrectomy (5/6Nx). 14 In these 3 AF models, we have evaluated the anti-AF effects of pioglitazone, 12 induction of heat shock protein (HSP), 13 and an antioxidant agent, 14 respectively.…”

mentioning

confidence: 99%