title: Cyclin A2 induces cardiac regeneration after myocardial infarction and prevents heart failure.
abstract: Mammalian myocardial infarction is typically followed by scar formation with eventual ventricular dilation and heart failure. Here we present a novel model system in which mice constitutively expressing cyclin A2 in the myocardium elicit a regenerative response after infarction and exhibit significantly limited ventricular dilation with sustained and remarkably enhanced cardiac function. New cardiomyocyte formation was noted in the infarcted zones as well as cell cycle reentry of periinfarct myocardium with an increase in DNA synthesis and mitotic indices. The enhanced cardiac function was serially assessed over time by MRI. Furthermore, the constitutive expression of cyclin A2 appears to augment endogenous regenerative mechanisms via induction of side population cells with enhanced proliferative capacity. The ability of cultured transgenic cardiomyocytes to undergo cytokinesis provides mechanistic support for the regenerative capacity of cyclin A2.
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032, USA.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Cheng
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Asai
authors.forename: Haiying
authors.initials: H
authors.lastname: Tang
authors.forename: Nurin H
authors.initials: NH
authors.lastname: Dashoush
authors.forename: Rina J
authors.initials: RJ
authors.lastname: Kara
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Costa
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Naka
authors.forename: Ed X
authors.initials: EX
authors.lastname: Wu
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Wolgemuth
authors.forename: Hina W
authors.initials: HW
authors.lastname: Chaudhry
mesh_terms: D000818:Animals; D002303:Cardiac Output, Low / Q000503:physiopathology / Q000517:prevention & control*; D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D019925:Cyclin A / Q000235:genetics / Q000502:physiology*; D056751:Cyclin A2; D005786:Gene Expression Regulation; D006321:Heart / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008822:Mice, Transgenic; D008940:Mitotic Index; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology
chemical_list: C508184:CCNA2 protein, mouse; D019925:Cyclin A; D056751:Cyclin A2