Deficiency of ataxia-telangiectasia mutated kinase modulates functional and biochemical parameters of the heart in response to Western-type diet

Abstract

Ataxia-telangiectasia mutated (ATM) kinase deficiency in humans associates with enhanced susceptibility to ischemic heart disease. Here, we provide evidence that ATM deficiency accelerates body weight gain and associates with increased cardiac preload, hypertrophy, and apoptosis in mice fed with Western-type diet (WD). Further investigations of the role of ATM deficiency in WD-induced alterations in function and biochemical parameters of the heart may provide clinically applicable information on treatment and/or nutritional counseling for patients with ATM deficiency.

Deficiency of ataxia‐telangiectasia mutated kinase attenuates Western‐type diet‐induced cardiac dysfunction in female mice

“…Following the 14‐week duration of WD or NC, mice were anesthetized using a mixture of isoflurane (2%) and oxygen (0.6 L/min). After which, Vevo 1100 imaging system (VisualSonics, Fujifilm) equipped with a 22‐ to 55‐MHz MS550D transducer was used in order to assess the structural and functional parameters of the heart (Wingard et al, 2021 ). Transthoracic short axis view at mid‐papillary level view was used to obtain M‐mode recordings, while doppler tracings were acquired from the apical four chamber view.…”

“…Transthoracic short axis view at mid‐papillary level view was used to obtain M‐mode recordings, while doppler tracings were acquired from the apical four chamber view. These recordings were used to measure and/or calculate the structural and functional parameters of the heart as described (Wingard et al, 2021 ).…”

“…Percent fibrosis was calculated by division of the total fibrosis by the total area of each image multiplied by 100. To examine WD‐induced lipid accumulation, mid‐cardiac cryosections (10 μm thick) were stained with Oil red O, and analyzed as described (Wingard et al, 2021 ).…”

“…Heart lysates were prepared in RIPA buffer supplemented with Halt protease inhibitor cocktail as described (Wingard et al, 2021 ). Equal amounts of proteins (50 μg) were resolved by SDS‐PAGE and transferred to PVDF membranes.…”

“…While the cardiovascular effects of WD during ATM deficiency are not fully elucidated, we have previously provided evidence that WD during ATM deficiency in male mice associates with accelerated weight gain, systolic dysfunction with increased preload, exacerbation of cardiac remodeling including increased hypertrophy and apoptosis, and alterations in inflammatory and metabolic signaling (Wingard et al, 2021 ). The objective of this study was to investigate the role of ATM deficiency in WD‐induced changes in functional and biochemical parameters of the heart in female mice.…”