Abstract 13287: Anti-Apoptotic BAG3 Gene in Tako-Tsubo Cardiomyopathy
Background and aim: Tako-tsubo cardiomyopathy (TTC) is a stress related acute cardiac condition characterized by transient myocardial stunning inducing left ventricular systolic dysfunction in absence of obstructive coronary artery disease. The pathogenesis of TTC is still unclear. BAG3 is an anti-apoptotic protein produced in myocardial cells whose expression can be increased by stressful stimuli. The relationship between a mutated BAG3 protein and an higher susceptibility to myocardial apoptosis induced by stressful trigger events has been hypothesized.
Aim of this study is verify the presence of BAG3 mutations in patients with TTC.
Methods: Mutation analyses with genomic DNA were performed in 16 patients (15 females; age 61.1 ± 13.2 years) enrolled according to the Mayo Clinic diagnostic criteria for TTC and in 10 sex and age matched healthy donors. Quantitative polymerase chain reaction (PCR) primers were designed to analyze all exons and their flanking noncoding regions of BAG3 gene. PCR products were then sequenced by reaction with Big Dye (ABI). Sequencing data were analyzed using a bioinformatics software for the detection of mutations in coding exons and in the 3’ untranslated region (3’UTR) of BAG3 mRNA.
Results: A mutation in coding region or in the 3’UTR of BAG3 has been detected in 12 patients (75%) with TTC and in none of controls (p=0.0009). Among TTC patients those with BAG3 mutation are younger (57.8 ± 13.2 vs 71.2 ± 6.9 years; p= 0.026) and have a significantly higher incidence of trigger events (11 vs 1 p = 0.045). Furthermore there is a trend for an higher rate of acute heart failure in this subgroup (9 vs 1; p = 0.075).
Conclusions: our data suggest that a reduced anti apoptotic action of mutated BAG3 protein could play a role in the occurrence of stress induced myocardial stunning in TTC patients.
- © 2012 by American Heart Association, Inc.