Deficiency of Ataxia-Telangiectasia Mutated Kinase Modulates Functional and Biochemical Parameters of the Heart in Response to Western-type Diet

Am J Physiol Heart Circ Physiol. 2021 Apr 30. doi: 10.1152/ajpheart.00990.2020. Online ahead of print.ABSTRACTAtaxia telangiectasia mutated kinase (ATM) deficiency exacerbates heart dysfunction late after myocardial infarction. Here, we hypothesized that ATM deficiency modulates Western-type diet (WD)-induced cardiac remodeling with an emphasis on functional and biochemical parameters of the heart. Weight gain was assessed in male wild-type (WT) and ATM heterozygous knockout (hKO) mice on weekly basis, while cardiac functional and biochemical parameters were measured 14 weeks post-WD. hKO-WD mice exhibited rapid body weight gain at weeks 5, 6, 7, 8 and 10 vs WT-WD. WD decreased percent fractional shortening and ejection fraction, and increased end systolic volumes and diameters to a similar extent in both genotypes. However, WD decreased stroke volume, cardiac output, peak velocity of early ventricular filling and aortic ejection time, and increased isovolumetric relaxation time (IVRT) and Tei index in vs WT-NC (normal chow). Conversely, IVRT, isovolumetric contraction time and Tei index were lower in hKO-WD vs hKO-NC and WT-WD. Myocyte apoptosis and hypertrophy were higher in hKO-WD vs WT-WD. WD increased fibrosis and expression of Collagen-1α1, MMP-2, and MMP-9 in WT. WD enhanced AMPK activation, while decreasing mTOR activation in Hko. Akt and IKK-α/β activation, and Bax, PARP-1 and Glut-4 expression were higher in WT-WD vs WT-NC, while NFкB activation and Glut-4 expre...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Source Type: research