Increased Myocardial GRP94 Amounts During Sustained Atrial Fibrillation

Vitadello, Maurizio; Ausma, Jannie; Borgers, M.; Gambino, Antonio; Casarotto, D; Gorza, Luisa

doi:10.1161/01.cir.103.17.2201

Cited by 28 publications

(25 citation statements)

References 36 publications

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“…32 Heat stress induces HSPs and prevents ventricular tachyarrhythmias caused by myocardial ischemia and reperfusion. 33 HSP expression is increased in both experimental 34 and clinical 8 AF. Higher levels of HSP expression are associated with a decreased risk of postoperative AF.…”

Section: Brundel Et Al Hsps Protect Against Atrial Fibrillation 1399mentioning

confidence: 94%

Induction of Heat Shock Response Protects the Heart Against Atrial Fibrillation

Brundel

Shiroshita-Takeshita

et al. 2006

Circulation Research

155

191

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Abstract-There is evidence suggesting that heat shock proteins (HSPs) may protect against clinical atrial fibrillation (AF).We evaluated the effect of HSP induction in an in vitro atrial cell line (HL-1) model of tachycardia remodeling and in tachypaced isolated canine atrial cardiomyocytes. We also evaluated the effect of HSP induction on in vivo AF promotion by atrial tachycardia-induced remodeling in dogs. Tachypacing (3 Hz) significantly and progressively reduced Ca 2ϩ transients and cell shortening of HL-1 myocytes over 4 hours. These reductions were prevented by HSP-inducing pretreatments: mild heat shock, geranylgeranylacetone (GGA), and transfection with human HSP27 or the phosphorylation-mimicking HSP27-DDD. However, treatment with HSP70 or the phosphorylation-deficient mutant HSP27-AAA failed to alter tachycardia-induced Ca 2ϩ transient and cell-shortening reductions, and downregulation (short interfering RNA) of HSP27 prevented GGA-mediated protection. Tachypacing (3 Hz) for 24 hours in vitro significantly reduced L-type Ca 2ϩ current and action potential duration in canine atrial cardiomyocytes; these effects were prevented when tachypacing was performed in cells exposed to GGA. In vivo treatment with GGA increased HSP expression and suppressed refractoriness abbreviation and AF promotion in dogs subjected to 1-week atrial tachycardia-induced remodeling. In conclusion, our findings indicate that (1) HSP induction protects against atrial tachycardia-induced remodeling, (2) the protective effect in HL-1 myocytes requires HSP27 induction and phosphorylation, and (3) the orally administered HSP inducer GGA protects against AF in a clinically relevant animal model. These findings advance our understanding of the biochemical determinants of AF and suggest the possibility that HSP induction may be an interesting novel approach to preventing clinical AF.

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Section: Brundel Et Al Hsps Protect Against Atrial Fibrillation 1399mentioning

confidence: 94%

Induction of Heat Shock Response Protects the Heart Against Atrial Fibrillation

Brundel

Shiroshita-Takeshita

et al. 2006

Circulation Research

155

191

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show abstract

“…Intriguingly, GRP94 is protective in cardiac pathologies, reducing cardiomyocyte necrosis in response to artificially induced Ca 2þ overload or simulated ischemic insult (Vitadello et al 2003). Furthermore, GRP94 expression is increased in hearts undergoing prolonged atrial fibrillation, hypothesized to have a protective role against injury (Vitadello et al 2001). GRP94 also plays a role in apoptosis, particularly when related to perturbations in Ca 2þ homeostasis.…”

Section: Grp94mentioning

confidence: 99%

Organellar Calcium Buffers

Prins¹,

Michalak²

2011

Cold Spring Harbor Perspectives in Biology

128

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“…The patients described in this study all suffered for prolonged periods of time from heart disease and/or AF. During such long periods of cardiac stress, cTnI might be protected from degradation through an increased expression of heat shock proteins 27,28 or an increased cTnI phosphorylation. 29 Further analysis of TnI isoform expression was performed by quantitative RT-PCR.…”

Section: Thijssen Et Al Troponin I Isoform Expression In Af 773mentioning

confidence: 99%

Troponin I Isoform Expression in Human and Experimental Atrial Fibrillation

Thijssen

Ausma²,

Gorza³

et al. 2004

Circulation

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Background-Atrial fibrillation (AF) is accompanied by re-expression of fetal genes and activation of proteolytic enzymes. In this study both aspects were addressed with respect to troponin I (TnI) isoform expression. Methods and Results-Western blotting and real-time reverse transcription-polymerase chain reaction were used to study TnI isoform expression in patients with paroxysmal or chronic AF and in goats after 1, 2, 4, 8, and 16 weeks of AF. In addition to cardiac TnI (cTnI), low expression of slow-twitch skeletal TnI (ssTnI) protein was found in 60% of patients in sinus rhythm or paroxysmal AF and in 8% of patients with chronic AF. In adult goat atrium, ssTnI protein expression was undetectable. Calcium-dependent degradation of cTnI protein was found in 1 or 2 of 6 animals after 1 to 4 weeks of AF. Although always low, ssTnI mRNA levels were significantly higher in patients who expressed ssTnI protein than in those who did not. Relative ssTnI mRNA expression was significantly lower in patients with paroxysmal AF and chronic AF than in those in sinus rhythm. In goats there was a tendency toward higher relative levels of ssTnI at the onset of AF followed by a normalization when AF had become sustained. Conclusions-Atrial re-expression of ssTnI during paroxysmal AF in patients and during the first 2 weeks of pacing-induced AF in goats does not seem to be part of the process of AF-associated cardiomyocyte dedifferentiation but seems to result from transient cardiomyocyte stress at the onset of AF.

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Increased Myocardial GRP94 Amounts During Sustained Atrial Fibrillation

Cited by 28 publications

References 36 publications

Induction of Heat Shock Response Protects the Heart Against Atrial Fibrillation

Induction of Heat Shock Response Protects the Heart Against Atrial Fibrillation

Organellar Calcium Buffers

Troponin I Isoform Expression in Human and Experimental Atrial Fibrillation

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