Document Type
Article
Publication Date
1-1-2014
Description
Background: Ataxia-telangiectasia results from mutations in ataxia telangiectasia mutated kinase (ATM) gene. We recently reported that ATM deficiency attenuates left ventricular (LV) dysfunction and dilatation 7 days after myocardial infarction (MI) with increased apoptosis and fibrosis. Here we investigated the role of ATM in the induction of inflammatory response, and activation of survival signaling molecules in the heart acute post-MI.
Methods and Results: LV structure, function, inflammatory response, and biochemical parameters were measured in wild-type (WT) and ATM heterozygous knockout (hKO) mice 1 and 3 days post-MI. ATM deficiency had no effect on infarct size. MI-induced decline in heart function, as measured by changes in percent fractional shortening, ejection fraction and LV end systolic and diastolic volumes, was lower in hKO-MI versus WT-MI (n=10 to 12). The number of neutrophils and macrophages was significantly lower in the infarct LV region of hKO versus WT 1 day post-MI. Fibrosis and expression of a-smooth muscle actin (myofibroblast marker) were higher in hKO-MI, while active TGF-β1 levels were higher in the WT-MI 3 days post-MI. Myocyte cross-sectional area was higher in hKO-sham with no difference between the two MI groups. MMP-9 protein levels were similarly increased in the infarct LV region of both MI groups. Apoptosis was significantly higher in the infarct LV region of hKO at both time points. Akt activation was lower, while Bax expression was higher in hKO-MI infarct.
Conclusion: ATM deficiency results in decreased dilative remodeling and delays inflammatory response acute post-MI. However, it associates with increased fibrosis and apoptosis.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Citation Information
Daniel, Laura L.; Daniels, Christopher R.; Harirforoosh, Saghar; Foster, Cerrone R.; Singh, Mahipal; and Singh, Krishna. 2014. Deficiency of Ataxia Telangiectasia Mutated Kinase Delays Inflammatory Response in the Heart Following Myocardial Infarction. Journal of the American Heart Association. Vol.3(6). https://doi.org/10.1161/JAHA.114.001286 ISSN: 2047-9980
Copyright Statement
© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.