Conditional depletion of the acetyltransferase Tip60 protects against the damaging effects of myocardial infarction. J Mol Cell Cardiol 2022 Feb;163:9-19
Date
10/06/2021Pubmed ID
34610340Pubmed Central ID
PMC8816866DOI
10.1016/j.yjmcc.2021.09.012Scopus ID
2-s2.0-85116932867 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
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.
Author List
Wang X, Wan TC, Lauth A, Purdy AL, Kulik KR, Patterson M, Lough JW, Auchampach JAAuthors
John A. Auchampach PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinJohn W. Lough PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Michaela Patterson PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Tina C. Wan PhD Research Scientist II in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AcetyltransferasesAnimals
Apoptosis
Cell Cycle
Lysine Acetyltransferase 5
Mice
Myocardial Infarction
Myocytes, Cardiac
Trans-Activators
