RGD Reference Report - Deficiency of ataxia telangiectasia mutated kinase delays inflammatory response in the heart following myocardial infarction. - Rat Genome Database

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Deficiency of ataxia telangiectasia mutated kinase delays inflammatory response in the heart following myocardial infarction.

Authors: Daniel, Laura L  Daniels, Christopher R  Harirforoosh, Saghar  Foster, Cerrone R  Singh, Mahipal  Singh, Krishna 
Citation: Daniel LL, etal., J Am Heart Assoc. 2014 Dec;3(6):e001286. doi: 10.1161/JAHA.114.001286.
RGD ID: 13204799
Pubmed: PMID:25520329   (View Abstract at PubMed)
PMCID: PMC4338722   (View Article at PubMed Central)
DOI: DOI:10.1161/JAHA.114.001286   (Journal Full-text)


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 α-smooth muscle actin (myofibroblast marker) were higher in hKO-MI, while active TGF-ß1 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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MMP9Humanmyocardial infarction  ISOMmp9 (Mus musculus)protein:increased expression:heart left ventricleRGD 
Mmp9Ratmyocardial infarction  ISOMmp9 (Mus musculus)protein:increased expression:heart left ventricleRGD 
Mmp9Mousemyocardial infarction  IEP protein:increased expression:heart left ventricleRGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp9  (matrix metallopeptidase 9)

Genes (Mus musculus)
Mmp9  (matrix metallopeptidase 9)

Genes (Homo sapiens)
MMP9  (matrix metallopeptidase 9)


Additional Information