Abstract P1026: Creg1 Inhibits Cardiomyocyte Proliferation And Promotes Myocardial Differentiation And Compaction During Postnatal Cardiac Development

Abstract

Introduction: Overexpression of cellular repressor of E1A-stimulated genes 1 (CREG1) promotes the formation of compact, contracting myocardium-like structures during cardiomyogenesis from embryonic stem cells. Cell biology studies suggest that CREG1 promotes differentiation and inhibits proliferation of developing cardiomyocytes. This study aims to understand the role of CREG1 during myocardial development in vivo . Methods: Cardiac tissues were harvested from wild-type (WT) and constitutive Creg1 knockout (KO) postnatal day 1.5 and 17 through timed mating of heterozygous Creg1 mice. Creg1 KO mice were compared with Creg1 WT littermates using immunoblotting, immunofluorescence, and methylene blue staining. Results: Postnatal day 1.5 Creg1 KO hearts showed lower levels of expression of slow skeletal muscle troponin I (TnI) compared with WT counterparts. No significant difference in expression was seen between WT and KO Creg1 hearts for myosin light chain 3 (MLC3), myosin heavy chain (MHC), and cardiac troponin I. Immunofluorescence staining revealed increased numbers of PCNA (Proliferating Cell Nuclear Antigen) positive nuclei in postnatal day 1.5 Creg1 KO hearts, suggesting enhanced cardiomyocyte proliferation after loss of CREG1. Methylene blue staining in postnatal day 17 hearts displayed decreased myocardial compaction in Creg1 KO mice. Conclusion: CREG1 may promote cardiomyocyte differentiation and inhibit proliferation during postnatal myocardial development. Ablation of CREG1 results in cardiac compaction defects. Our findings suggest an important role for CREG1 in cardiac development.