RGD Reference Report - Deficiency of ataxia telangiectasia mutated kinase modulates cardiac remodeling following myocardial infarction: involvement in fibrosis and apoptosis. - Rat Genome Database

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Deficiency of ataxia telangiectasia mutated kinase modulates cardiac remodeling following myocardial infarction: involvement in fibrosis and apoptosis.

Authors: Foster, CR  Daniel, LL  Daniels, CR  Dalal, S  Singh, M  Singh, K 
Citation: Foster CR, etal., PLoS One. 2013 Dec 16;8(12):e83513. doi: 10.1371/journal.pone.0083513. eCollection 2013.
RGD ID: 10053570
Pubmed: PMID:24358288   (View Abstract at PubMed)
PMCID: PMC3865210   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0083513   (Journal Full-text)

Ataxia telangiectasia mutated kinase (ATM) is a cell cycle checkpoint protein activated in response to DNA damage. We recently reported that ATM plays a protective role in myocardial remodeling following beta-adrenergic receptor stimulation. Here we investigated the role of ATM in cardiac remodeling using myocardial infarction (MI) as a model. METHODS AND RESULTS: Left ventricular (LV) structure, function, apoptosis, fibrosis, and protein levels of apoptosis- and fibrosis-related proteins were examined in wild-type (WT) and ATM heterozygous knockout (hKO) mice 7 days post-MI. Infarct sizes were similar in both MI groups. However, infarct thickness was higher in hKO-MI group. Two dimensional M-mode echocardiography revealed decreased percent fractional shortening (%FS) and ejection fraction (EF) in both MI groups when compared to their respective sham groups. However, the decrease in %FS and EF was significantly greater in WT-MI vs hKO-MI. LV end systolic and diastolic diameters were greater in WT-MI vs hKO-MI. Fibrosis, apoptosis, and alpha-smooth muscle actin staining was significantly higher in hKO-MI vs WT-MI. MMP-2 protein levels and activity were increased to a similar extent in the infarct regions of both groups. MMP-9 protein levels were increased in the non-infarct region of WT-MI vs WT-sham. MMP-9 protein levels and activity were significantly lower in the infarct region of WT vs hKO. TIMP-2 protein levels similarly increased in both MI groups, whereas TIMP-4 protein levels were significantly lower in the infarct region of hKO group. Phosphorylation of p53 protein was higher, while protein levels of manganese superoxide dismutase were significantly lower in the infarct region of hKO vs WT. In vitro, inhibition of ATM using KU-55933 increased oxidative stress and apoptosis in cardiac myocytes.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
myocardial infarction  ISOAtm (Mus musculus)10053570; 10053570 RGD 
myocardial infarction  IMP 10053570 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Atm  (ATM serine/threonine kinase)

Genes (Mus musculus)
Atm  (ataxia telangiectasia mutated)

Genes (Homo sapiens)
ATM  (ATM serine/threonine kinase)


Additional Information