Conditional depletion of the acetyltransferase Tip60 protects against the damaging effects of myocardial infarction

Autor: Tina C. Wan, Alexandra L. Purdy, John Lough, Xinrui Wang, Katherine R. Kulik, Michaela Patterson, Amelia Lauth, John A. Auchampach
Rok vydání: 2022
Předmět:
Zdroj: J Mol Cell Cardiol
ISSN: 0022-2828
DOI: 10.1016/j.yjmcc.2021.09.012
Popis: Injury from myocardial infarction (MI) and consequent post-MI remodeling is accompanied by massive loss of cardiomyocytes (CM), a cell type critical for contractile function that is for all practical purposes non-regenerable due to its profound state of proliferative senescence. Identification of factors that limit CM survival and/or constrain CM renewal provides potential therapeutic targets. Tip60, a pan-acetyltransferase encoded by the Kat5 gene, has been reported to activate apoptosis as well as multiple anti-proliferative pathways in non-cardiac cells; however, its role in CMs, wherein it is abundantly expressed, remains unknown. Here, using mice containing floxed Kat5 alleles and a tamoxifen-activated Myh6-MerCreMer recombinase transgene, we report that conditional depletion of Tip60 in CMs three days after MI induced by permanent coronary artery ligation greatly improves functional recovery for up to 28 days. This is accompanied by diminished scarring, activation of cell-cycle transit markers in CMs within the infarct border and remote zones, reduced expression of cell-cycle inhibitors pAtm and p27, and reduced apoptosis in the remote regions. These findings implicate Tip60 as a novel, multifactorial target for limiting the damaging effects of ischemic heart disease.
Databáze: OpenAIRE
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