TY - JOUR T1 - Southern Regional Meeting, New Orleans, February 18–20, 2016 JF - Journal of Investigative Medicine JO - J Investig Med SP - 488 LP - 634 DO - 10.1136/jim-2015-000035.1 VL - 64 IS - 2 A2 - , Y1 - 2016/02/01 UR - http://hw-f5-jim.highwire.org/content/64/2/488.1.abstract N2 - 1: ROLE OF CYCLIN DEPENDENT KINASE INHIBITOR P27 IN CARDIOMYOCYTE REGENERATIONSK SenH SadekUT Southwestern Medical Center, Dallas, TXPurpose of Study Neonatal mammalian hearts have the ability to undergo cardiomyocyte regeneration for a short period of time after birth through proliferation of pre-existing cardiomyocytes. This regenerative window is lost by the first week of life coinciding with cell cycle arrest. The exact mechanism of how postnatal cardiomyocytes regulate proliferation remains unclear. We hypothesize a specific cyclin-dependent kinase inhibitor p27Kip1 (p27) plays a prominent role in cardiomyocyte proliferation both in the neonatal period and in adults following myocardial injury.Methods Used Cardiomyocyte specific α-myosin heavy chain deletion of p27 using Cre recombinase (cKO) mice were harvested and compared with wild type (WT) mice in the postnatal period. Immunostaining using mitotic markers phospho-histone 3 (pH3) and Aurora B kinase (AurB) were used to quantify proliferation along with wheat germ agglutinin (WGA) to determine cell size differences. Cardiomyocyte and nucleation counts were done by collagenase digestion. Cardiac function was assessed using M-mode echocardiography. Conditional deletion of p27 in the adult heart was also investigated using a p27f/f αMHC MerCreMer mouse model (iKO) that allowed specific deletion of p27 following tamoxifen administration. These p27 iKO mice were induced to explore the re-activation of cardiomyocyte mitosis as well as return of function following ischemic injury.Summary of Results p27 cKO extended of the proliferative window up to an additional week (6-fold) with no harmful effect in cardiac function. Proliferation was no longer seen by 1 month of age. In the adult mice, p27 iKO showed re-activation of mitotic cardiomyocytes throughout the heart (5-fold). In addition, we showed a decrease in cell size (p=0.023) with no significant change in heart weight/body weight ratio. Following myocardial infarction (MI), p27 iKO mice similarly showed robust proliferation throughout the myocardium as well as a brisk … ER -