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Alteration of left atrial calcium handling protein induced atrial fibrillation in heart failure
고신의대 복음병원 순환기내과
구상호, 차태준, 최연주, 최인수, 유찬희, 허정호, 이재우
Background: Calcium plays important role in myocardial contractility and arrrhythmogenesis. There are very few studies about calcium handling process in HF atrial tissue and its relationship to atrial tachyarrhythmia. This study evaluated relation of calcium handling protein changes and subsequent AF development in HF. Methods: A rat myocardial infarction (MI) model was used. Two days after induction of MI, rats were randomized into 2 groups: the sham group, the MI+Iso group (isoproterenol 30 μg/kg/hr for 2 weeks, administrated 8 weeks after the MI). Echocardiography, AF induction, and atrial fibrous tissue content analysis were done. RT PCR and western blotting of SERCA, phospholamban(PLB), RyR2, and AF inducibility tests were done. Results: Ejection fractions were significantly decreased in MI+Iso group. Fibrosis quantification showed significantly increased left atrial fibrosis in MI+Iso. Duration and inducibility of AF were increased in MI+Iso group. Atrial calcium handling proteins mRNA expression and protein expression levels were decreased in MI+Iso group. SERCA2a/PLB mRNA ratio was increased in MI+Iso group. Conclusion: Changes of calcium handling proteins are important contributing factors for subsequent AF inducibility in HF.
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Sham

MI+Iso

EF%

86.0±2.3 (n=10)

47.2±8.1* (n=10)

Fibrosis%

0.22±0.03 (n=5)

3.37±0.46* (n=5)

AF Duration (sec)

12.4±7.9 (n=15)

441.8±216.1* (n=13)

SERCA2a Protein

0.51±0.06 (n=4)

0.30±0.05* (n=5)

SERCA2a mRNA  (NR)

1 (n=10)

0.10±0.02* (n=10)

PLB protein

1.00±0.11 (n=4)

0.65±0.11*  (n=5)

PLB mRNA (NR)

1 (n=10)

0.46±0.12* (n=10)

PLB/SERCA ratio

1 (n=10)

9.39±5.02 (n=10)

RyR2 protein

3.10±0.22 (n=4)

1.79±0.29* (n=5)

RyR2 mRNA (NR)

1 (n=10)

0.23±0.12*

Mean±SE,  *p<0.05 sham versus MI+Iso, NR: normalized ration



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