RATIONALE: In response to injury, the rodent heart is capable of virtually full regeneration via cardiomyocyte proliferation early in life. This regenerative capacity, however, is diminished as early as 1 week postnatal and remains lost in adulthood. The mechanisms that dictate postinjury cardiomyocyte proliferation early in life remain unclear. OBJECTIVE: To delineate the role of @entity8204 , a regulator of age-associated physiology, in regulating cardiac regeneration secondary to @entity583 ( @entity583 ) in neonatal and adult @entity19 hearts. METHODS AND RESULTS: @entity299 was induced in neonatal and adult hearts through experimental @entity583 via coronary ligation. Adult hearts demonstrated overt cardiac structural and functional remodeling, whereas neonatal hearts maintained full regenerative capacity and cardiomyocyte proliferation and recovered to normal levels within 1-week time. As early as 1 week postnatal, @entity8204 expression was found to have increased and was maintained at high levels throughout the lifespan. Intriguingly, 7 days after @entity583 , @entity8204 levels further increased in the adult but not neonatal hearts. Delivery of a @entity8204 mimic to neonatal hearts prohibited both cardiomyocyte proliferation and subsequent cardiac recovery post @entity583 . Conversely, locked nucleic acid-based anti- @entity8204 treatment diminished post- @entity583 @entity8204 upregulation in adult hearts and significantly improved post- @entity583 remodeling. In isolated cardiomyocytes, we found that @entity8204 directly regulated cell cycle activity and @entity204 via modulation of its targets, including @entity1379 , @entity1896 , and @entity14075 . CONCLUSIONS: @entity8204 is a critical regulator of cardiac repair and regeneration post @entity583 in neonatal hearts. Modulation of @entity8204 may be harnessed for cardiac repair in adult myocardium.

MicroRNA-34a Plays a Key Role in Cardiac Repair and Regeneration Following XXXX .

@entity1896 :: ('12443(Tax:10090)', 'Gene') :: ['Cyclin D1'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity8204 :: ('723848(Tax:10090)', 'Gene') :: ['miR-34a'] @entity1379 :: ('12043(Tax:10090)', 'Gene') :: ['Bcl2'] @entity299 :: ('MESH:D006331', 'Disease') :: ['Cardiac injury'] @entity14075 :: ('93759(Tax:10090)', 'Gene') :: ['Sirt1'] @entity583 :: ('MESH:D009203', 'Disease') :: ['myocardial infarction', 'MI'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death']
@entity583 :: (MESH:D009203,Disease) :: ['Myocardial Infarction']
