Abstract 16386: Increased Myocardial Expression of Thioredoxin-Interacting Protein, and Evidence of Nitrosative Stress in a Rat Model of Tako-Tsubo Cardiomyopathy
Background: Tako-Tsubo Cardiomyopathy (TTC) reflects catecholamine-induced global myocardial inflammation, which predominantly affects the left ventricular (LV) apex. Recent studies in rodent models have suggested that TTC may be engendered by shifts in β2-adrenoceptor-mediated intracellular signal transduction. However, the nexus between this change and initiation of myocardial inflammation remains uncertain. We therefore sought to evaluate the potential roles of the inflammasome activating α-arrestin thioredoxin-interacting protein (TxNIP), and of the generation of nitrosative stress (potentially resultant from β2-adrenoceptor/NOS coupling) in TTC.
Method: TTC-like inflammation was induced in 4-5 month old female Sprague-Dawley rats by single injection of isoprenaline. Effects on echocardiographic parameters and LV apical and basal expression of TxNIP and of 3-nitrotyrosine (3-NT), a marker of nitrosative stress, were determined 24 hours later. Quantitative immunohistochemical analyses of myocardial TxNIP and 3-NT content were performed by investigators blinded to treatment status.
Result: Isoprenaline induced significant reductions in apical radial strain (35.5±4.3 [SD] to 22.5±7.7%; p<0.05) and apical fractional shortening (61.0±6.0 to 47.4±12%; p<0.05). Consistent with presence of myocardial edema, LV wall thickness tended to increase (p=0.1). In control rats, mean myocardial content of TxNIP and 3-NT were 1.5±0.4 and 1.1± 0.2 arbitrary units (AU) respectively. In isoprenaline-treated rats, myocardial content of both TxNIP and 3-NT were increased, as shown in the Table.
Conclusion: This model of TTC is therefore associated with predominantly periapical increases in TxNIP expression, together with evidence of nitrosative stress. Pharmacological attenuation of TxNIP release and/or nitrosative stress may represent a potential therapeutic strategy in TTC.
- © 2013 by American Heart Association, Inc.