Deficiency of Ataxia Telangiectasia-mutated Kinase (ATM) Preserves Heart Function by Affecting Cardiac Remodeling in Response to Western-type Diet (WD) in Female Mice

WD and deficiency of ATM protein independently associates with heart disease. Previous work demonstrated that WD in male ATM deficient mice induces accelerated body weight gain and heart dysfunction (Am J Physiol Heart Circ Physiol. 2021;320:H2324-H2338). Conversely, WD in female ATM deficient mice attenuates weight gain and preserves heart function (unpublished). Here, we investigated the mechanism by which ATM deficiency preserves heart function in female mice. Female wild-type (WT) and ATM heterozygous knockout (hKO) mice, aged 6 weeks, were fed with normal chow (NC) or WD for 14 weeks. Heart sections were stained with Masson’s trichrome to quantify fibrosis, TUNEL-stained to quantify apoptosis, and WGA-stained to quantify myocyte hypertrophy. Data were analyzed using ANOVA followed by Student-Newman-Keuls test. WD significantly increased fibrosis in WT-WD mice, while no increase in fibrosis was observed in hKO-WD. WD significantly increased apoptosis (myocytes and non-myocytes) in both genotypes. Myocyte hypertrophy was increased only in WT-WD. Interestingly, the increase in apoptosis was significantly lower in hKO-WD, while the increase in hypertrophy was significantly higher in hKO-WD vs WT-WD.Thus, ATM deficiency preserves heart function in female mice with decreased myocardial fibrosis and apoptosis, and increased myocyte hypertrophy in response to WD