Haplodeficiency of Ataxia Telangiectasia Mutated Accelerates Heart Failure After Myocardial Infarction

BackgroundCell senescence is involved in the process of organ damage and repair; however, the underlying molecular mechanism needs to be further explored. Methods and ResultsSenescence‐related genes (ie, p21, p53, and ataxia telangiectasia mutated [ATM]) were shown to be elevated after myocardial infarction (MI) in both mouse and human hearts. Ten‐ to 12‐week‐old male wild‐type littermates (ATM+/+) and ATM heterozygous mice (ATM+/−) were subjected to MI. Cardiac echography showed that ATM haplodeficiency did not affect the survival rate but aggravated heart failure at day 28 post MI. Histologic analysis showed increased fibrosis in the noninfarct area of ATM+/− mice compared with that in ATM+/+ mice. Senescence‐associated β‐galactosidase staining showed that the number of senescent fibroblasts was decreased when ATM was haplodeficient both in vivo and in vitro. Costaining of α‐smooth muscle actin with p53 or p19 showed fewer senescent myofibroblasts in ATM+/− mouse hearts. Moreover, angiogenesis was also ...