{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T14:45:51Z","timestamp":1769093151064,"version":"3.49.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,7]]},"abstract":"\n Background<\/jats:title>\n Cell senescence is involved in the process of organ damage and repair; however, the underlying molecular mechanism needs to be further explored.<\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Senescence\u2010related genes (ie, p21, p53, and ataxia telangiectasia mutated [ATM]) were shown to be elevated after myocardial infarction (\n MI<\/jats:styled-content>\n ) in both mouse and human hearts. Ten\u2010 to 12\u2010week\u2010old male wild\u2010type littermates (\n ATM<\/jats:styled-content>\n +\/+<\/jats:sup>\n ) and\n ATM<\/jats:styled-content>\n heterozygous mice (\n ATM<\/jats:styled-content>\n +\/\u2212<\/jats:sup>\n ) were subjected to\n MI<\/jats:styled-content>\n . Cardiac echography showed that\n ATM<\/jats:styled-content>\n haplodeficiency did not affect the survival rate but aggravated heart failure at day 28 post\n MI<\/jats:styled-content>\n . Histologic analysis showed increased fibrosis in the noninfarct area of\n ATM<\/jats:styled-content>\n +\/\u2212<\/jats:sup>\n mice compared with that in\n ATM<\/jats:styled-content>\n +\/+<\/jats:sup>\n mice. Senescence\u2010associated \u03b2\u2010galactosidase staining showed that the number of senescent fibroblasts was decreased when\n ATM<\/jats:styled-content>\n was haplodeficient both in\u00a0vivo and in\u00a0vitro. Costaining of \u03b1\u2010smooth muscle actin with p53 or p19 showed fewer senescent myofibroblasts in\n ATM<\/jats:styled-content>\n +\/\u2212<\/jats:sup>\n mouse hearts. Moreover, angiogenesis was also examined using the endothelial markers\n CD<\/jats:styled-content>\n 31 both at early (day 7) and late stages (day 28) after\n MI<\/jats:styled-content>\n , and\n ATM<\/jats:styled-content>\n haplodeficiency reduced angiogenesis after\n MI<\/jats:styled-content>\n . Finally, cardiac fibroblasts were isolated from infarcted mouse heart and the medium were tested for its capacity of endothelial tubing formation, revealing that\n ATM<\/jats:styled-content>\n haplodeficiency led to lower vascular endothelial growth factor production from cardiac fibroblast and reduced capacity of endothelial tube formation in\u00a0vitro.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n The present study shows that\n ATM<\/jats:styled-content>\n haplodeficiency decreases fibroblast senescence and vascular endothelial growth factor production and impaired angiogenesis in response to\n MI<\/jats:styled-content>\n , leading to accelerated heart failure.\n <\/jats:p>\n 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