Cyclin A2 induces cardiac regeneration after myocardial infarction and prevents heart failure.
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.
Cheng
Richard K
RK
Department of Medicine, Columbia University, New York, NY 10032, USA.
Asai
Tomohiro
T
Tang
Haiying
H
Dashoush
Nurin H
NH
Kara
Rina J
RJ
Costa
Kevin D
KD
Naka
Yoshifumi
Y
Wu
Ed X
EX
Wolgemuth
Debra J
DJ
Chaudhry
Hina W
HW
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
C508184:CCNA2 protein, mouse; D019925:Cyclin A; D056751:Cyclin A2