title: Ectonucleotidase CD39-driven control of postinfarction myocardial repair and rupture.
abstract: Mechanical complications of myocardial infarction (MI) are often fatal. Little is known about endogenous factors that predispose to myocardial rupture after MI. Ectonucleoside triphosphate diphosphohydrolase (CD39) could be a critical mediator of propensity to myocardial rupture after MI due to its role in modulating inflammation and thrombosis. Using a model of permanent coronary artery ligation, rupture was virtually abrogated incd39-/-mice versuscd39+/+controls, with elevated fibrin and collagen deposition and marked neutrophil and macrophage influx. Macrophages were found to display increased surface expression of CD301 and CD206, marking a reparative phenotype, driven by increased extracellular ATP and IL-4 in the infarcted myocardium ofcd39-/-mice. A myeloid-specific CD39-knockout mouse also demonstrated protection from rupture, with an attenuated rupture phenotype, suggesting that complete ablation of CD39 provides the greatest degree of protection in this model. Absence of CD39, either globally or in a myeloid lineage-restricted fashion, skews the phenotype toward alternatively activated (reparative) macrophage infiltration following MI. These studies reveal a previously unrecognized and unexpected role of endogenous CD39 to skew macrophage phenotype and promote a propensity to myocardial rupture after MI.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, and.
authors.forename: Nadia R
authors.initials: NR
authors.lastname: Sutton
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, and.
authors.forename: Takanori
authors.initials: T
authors.lastname: Hayasaki
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical Center.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Hyman
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical Center.
authors.forename: Anuli C
authors.initials: AC
authors.lastname: Anyanwu
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, and.
authors.forename: Hui
authors.initials: H
authors.lastname: Liao
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, and.
authors.forename: Danica
authors.initials: D
authors.lastname: Petrovic-Djergovic
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, and.
authors.forename: Linda
authors.initials: L
authors.lastname: Badri
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical Center.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Baek
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, and.
authors.forename: Natalie
authors.initials: N
authors.lastname: Walker
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, and.
authors.forename: Keigo
authors.initials: K
authors.lastname: Fukase
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, and.|Section of Cardiology, Veterans Affairs Medical Center, Ann Arbor, Michigan, USA.
authors.forename: Yogendra
authors.initials: Y
authors.lastname: Kanthi
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, and.
authors.forename: Scott H
authors.initials: SH
authors.lastname: Visovatti
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, and.
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Horste
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, and.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Ray
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, and.|Section of Cardiology, Veterans Affairs Medical Center, Ann Arbor, Michigan, USA.
authors.forename: Sascha N
authors.initials: SN
authors.lastname: Goonewardena
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, and.|Department of Molecular and Integrative Physiology, University of Michigan Medical Center.
authors.forename: David J
authors.initials: DJ
authors.lastname: Pinsky
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology*; D010641:Phenotype; D012421:Rupture / Q000209:etiology*; D013927:Thrombosis / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000251:Adenosine Triphosphatases; C027201:ectoATPase