Journal article
Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family
ER Porrello, AI Mahmoud, E Simpson, BA Johnson, D Grinsfelder, D Canseco, PP Mammen, BA Rothermel, EN Olson, HA Sadek
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2013
Abstract
We recently identified a brief time period during postnatal development when the mammalian heart retains significant regenerative potential after amputation of the ventricular apex. However, one major unresolved question is whether the neonatal mouse heart can also regenerate in response to myocardial ischemia, the mostcommon antecedent of heart failure in humans. Here, we induced ischemic myocardial infarction (MI) in 1-d-oldmice and found that this results in extensive myocardial necrosis and systolic dysfunction. Remarkably, the neonatal heartmounted a robust regenerative response, through proliferation of preexisting cardiomyocytes, resulting in full functional recovery within 21 d. More..
View full abstractGrants
Awarded by National Heart, Lung, and Blood Institute
Funding Acknowledgements
We thank J. Richardson, J. Shelton, and the University of Texas Southwestern Histology Core for help with histopathology; C. Gilpin for assistance with electron microscopy; J. Cabrera for graphical assistance; and E. van Rooij and miRagen Therapeutics for providing the anti-miRs. This work was supported by a C. J. Martin Overseas Biomedical Fellowship from the National Health and Medical Research Council and National Heart Foundation of Australia, National Health and Medical Research Council of Australia Project Grant APP1033815 (to E. R. P.), a pre-doctoral fellowship award from the American Heart Association (AHA) (to A. I. M.), grants from the National Institutes of Health (NIH), the Donald W. Reynolds Center for Clinical Cardiovascular Research, the Leducq Foundation, and the Robert A. Welch Foundation (E.N.O.), a cardiovascular research scholar award from Gilead Sciences, an AHA Grant-in-Aid award (AHA12GRNT), and an NIH R01 Grant (1R01HL115275-01) (to H.A.S.).