EFFECTS OF ATAXIA TELANGIECTASIA-MUTATED KINASE (ATM) DEFICIENCY ON CARDIAC REMODELING IN RESPONSE TO WESTERN-TYPE DIET (WD) PRIOR TO AND FOLLOWING MYOCARDIAL INFARCTION
Honors in Biology
Date of Award
Thesis Professor Department
Cardiovascular diseases are the leading cause of mortality worldwide. Ataxia telangiectasia mutated kinase (ATM) is a checkpoint protein involved in cell cycle regulation. It is activated in response to genotoxic mediators such as double-stranded DNA damage or oxidative damage. Mutations in the ATM gene result in a multisystemic disease called ataxia-telangiectasia (A-T). Independently, a Western-type Diet (WD) and ATM protein deficiency are linked with heart disease, exacerbated cardiac remodeling, and myocardial infarction (MI). Our laboratory has previously shown that in male mice, the consumption of a WD during ATM deficiency is associated with the exacerbation of cardiac remodeling. This study investigated the effect of ATM deficiency on WD-induced cardiac remodeling parameters before and 1-day post-MI in a sex-specific manner using female and male mice. Age-matched wild-type (WT) and ATM heterozygous knockout (hKO) mice were fed with normal-chow (NC) or WD for 14 weeks. MI was induced by ligation of the left anterior descending coronary artery (LAD) with a 7-0 polypropylene suture. After the study period, 14 weeks post-WD feeding and 1-day post-MI, the heart was removed through an opening in the diaphragm region. Heart sections were stained with Masson's trichrome to quantify fibrosis, TUNEL-stained to quantify apoptosis, infarct size, and infarct thickness, and wheat germ agglutinin-stained to quantify myocyte hypertrophy. In WT female mice, WD increased myocardial fibrosis, myocyte hypertrophy, and apoptosis at baseline compared to NC. However, in hKO-WD female mice, apoptosis was significantly lower, and hypertrophy was significantly higher than in WT-NC female mice at baseline. Intriguingly, no significant difference in apoptosis, infarct size, and infarct thickness was observed in both genotypes and genders 1-day post-MI. Thus, our data suggest that 1) ATM deficiency plays a cardioprotective role in female mice responding to WD, as it reduces apoptosis and increases hypertrophy at baseline, and 2) sex-specific cardioprotective effects of ATM deficiency in female mice were not observed 1-day post-MI in response to WD.
East Tennessee State University
Honors Thesis - Open Access
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Ramirez, Paulina, "EFFECTS OF ATAXIA TELANGIECTASIA-MUTATED KINASE (ATM) DEFICIENCY ON CARDIAC REMODELING IN RESPONSE TO WESTERN-TYPE DIET (WD) PRIOR TO AND FOLLOWING MYOCARDIAL INFARCTION" (2023). Undergraduate Honors Theses. Paper 798. https://dc.etsu.edu/honors/798
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